Research Awards Nationwide

This year’s Research Awards Nationwide is searchable. Please use the dropdown boxes to search by topic, state, or grant. If no topic or state is selected, all the information for that area will be displayed.

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Select a Grant All ALA/AAAAI Allergic Respiratory Disease Award ALA/AAF Senior Investigator Award ALA/CHEST Foundation Asthma Clinical Patient Care Research Grant ALA/CHEST Foundation Career Investigator Award ALA/NSF Pickwick Award ALA/NTM Non Tuberculosis Mycobacterium Award Asthma Clinical Research Centers (ACRC) Network Biomedical Research Grant Career Investigator Award Clinical Patient Care Research Grant Dalsemer Research Grant DeSouza Research Award Lung Cancer Discovery Award Lung Health Dissertation Grant Senior Research Training Fellowship Social Behavioral Research Grant

• Tracy Adair-Kirk, PhD
  Washington University in St. Louis, St. Louis, MO
  Biomedical Research Grant
  How Does Smoking Destroy the Lungs?

  Although it is known that smoking is the principal risk factor for developing emphysema, there are still many unknowns about the exact way in which this occurs. Cigarette smoke induces inflammatory cells to enter the lung releasing enzymes that break down critical proteins of elastic fibers, key lung structures that allow the stretch and recoil essential for normal lung function. These cells also produce substances called oxidants that promote the development of emphysema by damaging lung cells and inhibiting protective enzymes. The researchers have found that oxidants can also damage elastin, the main component of elastic fibers, making it more susceptible to breakdown by enzymes. Understanding the way in which oxidants cause damage will provide new insight into development of emphysema and may enhance scientists' ability to develop strategies to prevent disease from beginning.

• Scott Alper, PhD
  National Jewish Health, Denver, CO
  Biomedical Research Grant
  Seeking Genes That Affect Asthma and COPD

  The researchers are investigating the possibility of modifying inflammation during the progression of disease as an approach to developing novel diagnostic and treatment options. They will use immune cells to identify novel genes that regulate inflammation. They will compare the data generated by these cells to known lung disease-specific information from human patients in order to identify novel genes that regulate inflammatory lung diseases. These candidate disease genes will be further studied in mouse models of lung disease. The novel genes found could be used for better diagnosis and management of at-risk patients, and could lead to alternate monitoring strategies and prevention strategies. The novel genes could also be potential targets for the development of new treatments.

• Philip Arlen, PhD
  MD Anderson Cancer Center Orlando, Orlando, FL
  Clinical Patient Care Research Grant
  Finding The First Signs of Lung Cancer in the Blood

  X-rays, CT scans and molecular markers can help detect cancer at earlier stages, but these tests are not always precise. The researchers will investigate whether a simple blood test can be used to detect lung cancer. The test, called the Cancer Recognition (CARE), measures an antibody that is produced in response to a protein made by cancer cells. Preliminary results have shown that high levels of the antibody are correlated with the presence of lung cancer. The researchers will further evaluate the effectiveness of the test using blood from diagnosed lung cancer patients before and after treatment. They hope to develop a comprehensive detection test that harnesses the power of the immune system, taking advantage of the body's natural ability to sense the changes the lungs undergo as they become cancerous.

• Ralph Arlinghaus, PhD
  University Of Texas M.D. Anderson Cancer Center, Houston, TX
  Lung Cancer Discovery Award
  Treating Lung Cancer by Reversing a Genetic Defect in Tumors

  Non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer cases. The researchers have identified a protein called c-Abl kinase that is activated in some NSCLC cells and may contribute to the abnormal growth of these cancer cells. Part of the reason that c-Abl is activated is because a gene called FUS1 is defective in about 80% of lung cancer patients. The researchers will further investigate why c-Abl is activated in some NSCLC cells. In a mouse model, they will study whether combining drugs that inhibit c-Abl with current therapies for NSCLC increase their effectiveness. The research may lead to a potential target for lung cancer therapy in humans, and might contribute to the development of more advanced methods of early detection to prevent lung cancer.

• Asthma Clinical Research Centers
  Study of Asthma and Nasal Steroids (STAN)
  Co-Funded by the National Institutes of Health's National Heart, Lung and Blood Institute

  
  

  "This research is important because it will allow us to determine if treating sinonasal disease in patients with asthma also affects their asthma management"
  - Anne E. Dixon, MD, University of Vermont, STAN Lead PI

  Rhinitis and sinusitis are significant causes of morbidity, associated with poor asthma control and increased health care utilization. While the coexistence of asthma and sino nasal disease is well recognized, the interaction between the two processes is not well understood. In previously conducted ACRC trials, researchers have found that over 70% of asthmatics report sinusitis, rhinitis or both. This study will determine if the treatment of chronic sinusitis and rhinitis with nasal steroids improves asthma control, lung function and quality of life in patients with poorly controlled asthma and chronic rhinitis/sinusitis. Four hundred participants aged 12 and over will be randomly assigned to treatment with a nasal steroid or a placebo. The results of this study could provide significant new data to guide therapy in patients with poorly controlled asthma.

• Asthma Clinical Research Centers
  Study of Soy Isoflavones in Asthma (SOYA)
  Co-Funded by the National Institutes of Health's National Heart, Lung and Blood Institute

  
  

  "The SOYA study, which is nearing completion, will provide important new information on the potential role of a novel treatment for asthma, one that is inexpensive and safe. The ALA, with support from the NIH, has been instrumental in enabling the ACRC network to perform this study."
  - Lewis J. , MD, Northwestern University,SOYA Lead PI

  One possible reason for the increase in asthma prevalence and severity seen over the past decades is the change in diet. Epidemiological and interventional studies designed to identify a key nutrient or antioxidant vitamin that may be responsible for the increase in disease severity have produced inconsistent results. In previous ACRC trials, researchers have reported an association between low soy genistein intake and more severe asthma. This study will test the novel hypothesis that dietary supplementation with soy isoflavones is an effective treatment in patients with poorly controlled asthma. The study will include 360 patients, age 12 and over, with low dietary soy intake, and taking either inhaled corticosteroids or leukotriene modifiers for poorly controlled asthma. Participants will be randomly assigned to either a soy isoflavone supplement or placebo. Results will not only increase the understanding of the role of diet in asthma but could potentially identify a novel, safe and relatively inexpensive treatment for patients with asthma.

• Asthma Clinical Research Centers
  Effect of Positive Airway Pressure on Reducing Airway Reactivity in Patients with Asthma (CPAP)
  Co-Funded by the National Institutes of Health's National Heart, Lung and Blood Institute

  
  

  "The CPAP trial is a prime example of translational research. This study will be a new way to treat asthma without medications."
  - Mike Busk, MD, formerly of Indiana University, CPAP Lead-PI
  

  The development of alternative methods to drug use in improving asthma control is necessary. This study will test whether the use of CPAP, a current treatment for sleep apnea will improve asthma control. CPAP is a way of rthymically increasing airway pressure by applying external pressure through the nose or mouth to prevent large airway collapse during sleep. The researchers propose that applying the same rthymic pressure to the smaller airways will lessen the airway constriction that occurs during an asthma attack. The results of this study may lead to prescribing CPAP to patients with difficulties in achieving asthma control. This proof-of-principle clinical trial will randomize 192 participants, with stable documented asthma and who do not have sleep disorders, into one of three treatment groups for 12 weeks. Treatment arms include: nocturnal CPAP 10 cm H2O, nocturnal CPAP 5 cm H2O and nocturnal sham CPAP (<1 cm of H2O).

• Asthma Clinical Research Centers
  Long-acting Beta Agonist Step Down Study (LASST)
  Co-funded by GlaxoSmithKline.

  
  

  "One of the most common dilemmas currently faced by practicing physicians is how to reduce therapy once asthma is controlled on combination ICS/LABA. A study evaluating outcomes of reducing treatment with long term followup and using outcomes relevant to patients and clinicians is needed".
  - Linda Rogers, MD New York University, LASST Lead PI
  

  Current asthma guidelines recommend stepping down therapy once asthma is controlled for at least 3 months. For patients treated with inhaled corticosteroids (ICS) alone, a dose reduction of 25-50% to a minimal dose that controls disease is established. However, the optimal approach to reducing treatment in patients with asthma that is well controlled on fixed dose combination ICS/LABA are not clear. The study will compare three approaches of care to patients with asthma well-controlled for three months on combination ICS/LABA therapy: reduction of ICS dose and maintenance of LABA, initial discontinuation of LABA with continuation of ICS, and continuation of stable dose ICS/LABA. The data will allow the determination of the optimal treatment strategy defined as that which results in the lowest rate of treatment failure over 48 weeks of follow- up. Additional exploratory analyses will include assessing risk factors for step-down failure and assessing the optimal duration of time that asthma control should be maintained before therapy is de-escalated.

  Co-funded by GlaxoSmithKline

• Kameswara Rao Badri, PhD
  University of Chicago, IL
  American Lung Association Interstitial Lung Disease Scholar
  American Lung Association Interstitial Lung Disease Scholar

  Pulmonary fibrosis is a disease marked by scarring of the tissue inside and between the air sacs in the lungs. When the scar forms, the tissue becomes stiff and thicker. This makes it harder for oxygen to pass through the walls of the air sac into the bloodstream. Once the lung tissue becomes scarred, the damage cannot be reversed.
  
  

  "I am thankful to the American Lung Association for laying the foundation for my long-term goal of becoming an independent researcher."

  As pulmonary fibrosis develops, an increasing number of connective tissue cells called fibroblasts and myofibroblasts are formed. Myofibroblasts are cells with characteristic features of both fibroblasts and smooth muscle cells. These cells are important in wound repair responses and tissue remodelling. In pulmonary fibrosis, too many fibroblasts and myofibroblasts accumulate in lung as a result of different cellular events, depositing large amounts of collagen and producing excessive scarring. TGF-ßI plays a central role in these cellular events and represents the most powerful fibrosis promoting growth factor identified so far. Fibroblasts and myofibroblasts are activated by TGF-ßl.
  
  With the help of an American Lung Association Dalsemer Research Grant, Dr. Badri is investigating the role of a molecule called P311 that regulates TGF-ßl expression. He will determine whether the lack of P311 in mice will protect against development of the disease. He will induce IPF in the mice using a drug called bleomycin. "Molecules that regulate TGF-ßI will regulate activated fibroblasts and myofibroblasts," Dr. Badri says. "Any molecule that regulates TGF-ßI and the numbers of activated fibroblasts and myofibroblasts is definitely of interest for the treatment of pulmonary fibrosis. So it is important to find a target, such as P311, that controls TGF-ßl levels." The ultimate goal, he says, is to reduce the number of fibroblasts and myofibroblasts through the regulation of different molecular mechanisms associated with the development of IPF. Dr. Badri adds that research involving mouse aortas has shown that P311 also regulates vascular contraction, so it may also be involved in hypertension. "This means our findings may also have implications for other lung diseases that involve the pulmonary blood vessels," he says.
  
  "I am thankful to the American Lung Association for laying the foundation for my long-term goal of becoming an independent researcher in this field," he notes. "This funding will also allow me to gather data which will permit me to submit proposals for federal funding."

• Sinem Beyhan, PhD
  University Of California, San Francisco, San Francisco, CA
  Senior Research Training Fellowship
  How Does a Common Mold Cause a Dangerous Lung Infection

  In persons with damaged immune system, inhaling the mold H. capsulatum can result in a lifethreatening disease called histoplasmosis. Positive histoplasmin skin tests occur in as many as 80% of the people living in areas where H. capsulatum is common. In the United States, H. capsulatum is endemic in the Mississippi and Ohio River Valleys. It is found in mold form in the soil. Infants, young children, and older persons, in particular those with chronic lung disease, are at increased risk for severe disease. The researchers will study how H. capsulatum causes respiratory infections. Findings from this study can be used to develop vaccine and treatment strategies against H. capsulatum infections.

• Rudra Bhowmick, PhD
  University Of Massachusetts, Worcester, MA
  Senior Research Training Fellowship
  Stopping Bacteria from Invading the Bloodstream During Lung Infection

  Lung infection by S. pneumoniae results in an outpouring of defense cells called polymorphonuclear leukocytes (PMNs) into the lung, leading to tissue damage and diminished gas exchange—the transfer of oxygen from inhaled air into the blood and the transfer of carbon dioxide from the blood into the exhaled air. A sugar coating protects S. pneumoniae from being efficiently killed by PMNs. Cells that line the lung, called epithelial cells, usually provide an important barrier to microbial invasion, but S. pneumoniae is somehow able to cross this cell barrier to cause a life-threatening bloodstream infection. The researchers hypothesize that the movement of PMNs into the lung in response to bacterial infection may itself disrupt the cell barrier, allowing the bacteria to penetrate it and gain access to the bloodstream. To better understand this bloodstream invasion, the researchers will use a mouse model to test drugs for the ability to block the outpouring of PMN and the movement of S. pneumonia across the cell barrier, thus protecting the mice from otherwise lethal lung infection. These studies may lead to new ways to prevent serious blood infections following S. pneumoniae lung infection in humans.

• Alina Boesteanu, PhD
  Drexel University, Philadelphia, PA
  Biomedical Research Grant
  Stopping the Flu Viruses "Reproductive System" Could Lessen Disease

  There is a need for development of new drugs for influenza. Drugs that do not target the virus directly but instead target the host cell machinery that is used by the virus in order to survive and multiply may be less prone to resistance. Extensive research has demonstrated that influenza virus hijacks mechanisms within the cell that control cellular activation. The researchers have found that lack of a specific signaling protein that controls cellular activation also restricts virus replication. They have found that treatment of normal mice with a drug that specifically targets this signaling molecule protected these mice from succumbing when infected with a high dose of the virus. The researchers will explore the virus replication and survival of lung cells infected with the influenza virus. Their research could be used to develop a drug that targets the signaling molecule to reduce the lung viral load and improve unwanted symptoms associated with influenza virus infection.

• Tracey Bonfield, PhD
  Case Western Reserve University
  American Lung Association Obstructive Lung Disease Scholar
  Obstructive Lung Disease Scholar

  Much of the illness caused by asthma is associated with abnormal activation of the immune system. The inflammation in the airways of a person with asthma is continuous and robust, which can ultimately result in airway remodeling and structural changes. This in turn can lead to reduced lung function. There are many pharmaceutical therapies used in asthma, but some people's asthma cannot be controlled with current treatments. Tracey Bonfield, PhD, is studying mesenchymal stem cells as a potential new treatment in uncontrolled chronic asthma. These stem cells, produced in the bone marrow, are precursor cells. This means that they can grow into a variety of different types of cells throughout the body. Mesenchymal stem cells have been shown to repress inflammation and the activity of immune cells called T cells, both major contributors to asthma.
  
  Using an American Lung Association Biomedical Research Grant, Dr. Bonfield is studying mesenchymal stem cells' effects on animal models of acute and chronic asthma that mimic many of the disease characteristics seen in human asthma. The model imitates exacerbations seen in an acute episode of asthma. The chronic model mimics many of the hallmarks of chronic asthma, with airway remodeling and decreased lung function.
  
  

  "We have been able to demonstrate that mesenchymal stem cells have the unique capacity to reverse many of the pathologies of chronic and acute asthma."

  "We have been able to demonstrate that mesenchymal stem cells have the unique capacity to reverse many of the pathologies of chronic and acute asthma using these models of human asthmatic lung disease," Dr. Bonfield says. "Although we have found that the mesenchymal stem cells have this capacity, we still don't know how they are doing it." The current focus is on examining three possibilities: whether the changes are caused by the cells themselves, whether they are the result of a products made by the cells, or whether they are a result of communication between the stem cells and the body, which allows the body to repair itself.
  
  "If the changes are caused by mesenchymal cells, it might be possible to create a potential therapy based on the findings," Dr. Bonfield states. "If the treatment requires products produced by the stem cells themselves, it might mean that patients would have a new product they could take, as they do with current asthma therapy." Both of these options may require more than one dosing. However if the cell-based therapy actually changes the body's immune system, it might be possible to give the treatment once and the cells would then take over, continually making what the body needs to fight the changes in the lung. Dr. Bonfield's laboratory is studying how long these stem cells would be effective in treating asthma in this case.

• Emilie Bourdonnay, PhD
  University Of Michigan, Ann Arbor, MI
  Senior Research Training Fellowship
  Getting the Lungs to Improve Their Defense against Pneumonia

  In the lung, cells called alveolar macrophages (AMs) are strategically located to defend the lung against infectious agents. These cells fight infections by ingesting and killing microbes. During lung infections, the body produces a biochemical messenger called prostaglandin E2 (PGE2) at high levels. Even in the absence of infection, PGE2 is overproduced when the immune system is suppressed in some people, such as those with AIDS. PGE2 suppresses AMs, and inhibits their microbial killing functions. The researchers will study the mechanisms that regulate how AMs kill microbes, and how this AM killing function is impaired by PGE2. The results could lead to novel therapeutic approaches to improve lung immune defenses and to treat pneumonia.

• James Bridges, PhD
  Cincinnati Children's Hospital Medical Center, Cincinnati, OH
  Biomedical Research Grant
  Knowing Protein's Role in Airway Remodeling May Lead to New Treatments

  Enlargement of the smooth muscle layer surrounding the airways, also known as airway remodeling, is a common feature of many chronic lung diseases including asthma, and chronic obstructive pulmonary disease (COPD). The mechanisms contributing to airway remodeling are poorly understood but the researchers believe a protein called hypoxia inducible factor 2a (HIF2a) may play a role. The researchers will determine the role of HIF2a in airway smooth muscle using mouse models of allergen-induced asthma. They will use mice that have increased or decreased levels of HIF2a in airway smooth muscle cells. The long-term goal of this research is to identify how smooth muscle becomes dysfunctional, and to develop novel treatment targets for chronic airway disease.

• Estelle Cormet-Boyaka, PhD
  Ohio State University, Columbus, OH
  Biomedical Research Grant
  Finding How Cadmium Accumulation in the Lungs Leads to Lung Disease

  Cadmium, a toxic heavy metal, is an air pollutant found in diesel exhaust and cigarette smoke. Due to its long half-life of 20 to 30 years (the amount of time it takes for cadmium to decrease by half), cadmium accumulates in the body. Cadmium inhalation has been linked to lung cancer and COPD but the mechanism by which cadmium affects the lung is poorly understood. The researchers hypothesize that CFTR, a protein which is lacking in people with cystic fibrosis, may be involved. The researchers will study the mechanism by which cadmium affects the production and function of CFTR and leads to inflammation. Understanding how cadmium inhalation affects lung function will help develop new strategies to prevent and/or protect against cadmium.

• Olga Danilchanka, PhD
  University Of Alabama, Birmingham, AL
  Senior Research Training Fellowship
  Facilitating the Penetration of Anti-TB Drugs into the Germ

  Tuberculosis infection mainly occurs in a specific type of cell in the lungs, called macrophages. These cells are designed to clean and protect the lung by attacking bacteria. However, the bacterium that causes TB, Mycobacterium tuberculosis (Mtb), is protected from many toxic compounds that are produced by macrophages by the specific make-up of its outmost layer, the outer membrane. The researchers' goal is to identify and characterize the proteins that make up the surface of Mtb cells and to determine how they are protective against killing of Mtb inside the human body. They will study a protein called MtpA that could be used to shuttle antibiotics into the bacterium. They will determine whether the presence of this protein allows drugs to pass through the otherwise impermeable outer membrane of Mtb. Characterization of this protein may lead to the development of better TB treatments that can reduce the duration of TB therapy

• J. Lucian Davis, MD, MAS
  University Of California, San Francisco, San Francisco, CA
  Clinical Patient Care Research Grant
  New DNA Test May Cut Down on Unneeded TB Treatment

  Public health interventions such as quarantining patients in the hospital, and interviewing close family, friends and coworkers for evidence of TB usually begin prior to receiving an actual diagnosis of TB. This is due to the inadequacies of the existing tests for TB – a sputum test that takes two months to provide final results, and other rapid tests that both under-diagnoses and over-diagnoses TB. As a result, many patients who are suspected of TB suffer medication side effects and may not be treated for the true cause of their underlying respiratory symptoms. A new automated DNA fingerprinting test for TB, GeneXpert, has been found to be an easier test to use and is potentially more accurate; however it is not widely used because the test is complex, and there is a lack of clear evidence that TB treatment can be safely discontinued in patients who test negative. The researchers will determine if this test provides a rapid, accurate alternative to the existing approaches cutting down on unnecessary treatment and public health interventions among patients who are suspected of having TB.

• Mary Ann De Groote, MD
  Colorado State University, Fort Collins, CO
  American Lung Association/Ntm Info & Research, Inc. Career Investigator Award
  Discovering New Drugs To Fight Mycobacteria

  A family of bacteria called the non-tuberculous Mycobacteria can infect both healthy people and people with compromised body defenses when they are exposed through aerosols, inoculations or medical/surgical procedures. One in particular, Mycobacterium abscessus, can cause destructive lung disease and skin infections that can be very hard to treat because the bacteria tend to be resistant to many antibiotics. The researchers will work with Dr. Scott Franzblau at the University of Illinois, Chicago, an expert at discovering drugs against the mycobacteria family to determine the most effective antibiotic therapies. The next step will be to test the most active compounds in an animal model validated by Dr. Diane Ordway at Colorado State University. This research may be useful in discovering new drugs against M. abscessus.

• Bouke Catherine De Jong, MD, PhD
  New York University, New York, NY
  Biomedical Research Grant
  Studying Variants of TB to Find an Effective Vaccine

  One way to increase the understanding of immunity to TB is to study differences in "behavior" between different strains of the TB bacterium and to search for bacterial genes that cause those differences. The researchers will study a variant of M. tuberculosis, called M. africanum, which is abundant in West Africa. M. africanum patients and their household members are less likely to mount an immune re- sponse to a protein called ESAT-6, which is produced by the TB bacteria and is essential to their causing disease. Preliminary findings suggest that M. africanum secretes less ESAT-6 than M. tuberculosis. The researchers will study the mechanism of defective ESAT-6 secretion in M. africanum by manipulating a bacterial gene that is thought to explain the difference. A better understanding of how the ESAT-6 protein works could form the basis for new drugs that would interrupt its secretion. ESAT- 6 is part of a candidate TB vaccine, and this study will inform TB vaccine development, which aims to prevent lung disease caused by TB.

• Jeffrey Engelman, MD, PhD
  Massachusetts General Hospital, Boston, MA
  Lung Cancer Discovery Award
  Can We "Teach" Cancer Cells to Die "On Time"

  Specialized treatments termed targeted therapies are increasingly being used to treat advanced lung cancer. These treatments aim to disrupt specific processes needed for a cancer cell's growth and survival. Yet, some cancer cells are intrinsically more resistant to targeted therapies. The researchers will study a protein named BIM which governs a process called apoptosis, or programmed cell death. Preliminary studies have found that patients whose cancers have low BIM levels received less benefit from the same targeted therapy as patients whose cancers (harboring the same genetic mutations) have high levels of BIM. The researchers have identified new strategies to induce cell death in the cancers lacking BIM. They aim to determine which patients will have the greatest benefit from targeted therapies, and to identify alternative treatments that may be more effective for cancers with low BIM and normally have reduced responses to targeted treatments.

• Ming-Hui Fan, MD
  University Of Pittsburgh, Pittsburgh, PA
  Dalsemer Research Grant
  A Novel Protein May Protect Lungs Against Scarring After Injury

  Fibroblast activation protein (FAP) has the ability to break down scar tissue in the lung. It is produced in the developing embryo and production is turned off shortly after birth. While not produced in normal healthy adult tissues, production is turned on in the setting of injury and wound healing, cancer, and diseases where organs become increasingly scarred and nonfunctional, such as pulmonary fibrosis. The researchers have found mice bred to be deficient in FAP have decreased survival and increased lung scarring. This suggests a protective role for FAP in preventing progression to pulmonary fibrosis after lung injury. The researchers will study the way in which FAP protects against the development of pulmonary fibrosis after lung injury. This research may ultimately lead to new treatment approaches for IPF.

• Ramesh Ganju, PhD
  Ohio State University, Columbus, OH
  American Lung Association Lung Cancer Scholar
  Lung Cancer Discovery Award

  "This research will hopefully lead to much needed treatments for NSCLC and could not have been possible without the support of the American Lung Association."

  About 85% to 90% of lung cancers are non-small cell lung cancer (NSCLC). Many patients with the disease become resistant to chemotherapy, and fewer than 20% of patients live beyond five years after diagnosis. Dr. Ganju is using an American Lung Association Lung Cancer Discovery Award to investigate potential novel treatments to extend the lives of patients with NSCLC. He is focusing on receptors called CB1 and CB2 found on cells that regulate the progression and spread of NSCLC to other organs and systems. Natural brain compounds called endocannabinoids, which are similar to THC—the active ingredient in marijuana—bind to CB1 and CB2. Dr. Ganju will test these compounds' effect on the growth and spread of lung cancer in a mouse model that is genetically engineered to develop lung cancer. "We believe endocannabinoids inhibit tumor growth, but this action is blocked by an enzyme called fatty-acid amide hydrolase (FAAH), which degrades, or breaks down, endocannabinoids," Dr. Ganju says.

  His first goal is to find out whether FAAH is being produced in lung cancer tumor samples. If this is the case, he will examine whether blocking FAAH might allow endocannabinoids to slow down or stop lung cancer growth. He will treat mice that develop NSCLC with a substance that inhibits FAAH, to find out if this treatment will increase the concentration of endocannabinoids and allow them to block tumor growth. He will also give NSCLC mice a direct treatment with endocannabinoids, to see whether the compounds have an effect on tumor growth and spread.

  Finally, he will examine genetically engineered mice that have a mutation that causes them to develop drug-resistant tumors. He will treat these mice with endocannabinoids and FAAH inhibitors to see if one or both treatments can be used successfully against drug-resistant tumors to inhibit lung cancer growth. This research would not have been possible without the American Lung Association grant, Dr. Ganju says. "We had initial data, but we didn't have money to proceed," he says. "This grant will help us to establish all of these models that could lead to new treatments for NSCLC. This is especially imperative considering the resistance of this lung cancer to chemotherapy and the poor prognosis of NSCLC patients."

• Elena Goncharova, PhD
  University of Pennsylvania,Philadelphia, PA
  Biomedical Research Grant
  Acute Lung Injury Scholar

  Elena Goncharova became interested in pulmonary arterial vascular smooth muscle cells while receiving her PhD in cardiology in Russia. When she came to the University of Pennsylvania for her postdoctoral studies, she began to study smooth muscle cells in a rare lung disease called pulmonary lymphangioleiomyomatosis (LAM), and found her calling. In LAM, smooth muscle cells grow abnormally; invading the airways, as well as blood and lymph vessels. "I worked with smooth muscle cells for years and have a long-term interest in smooth muscle cell behavior in diseased conditions," she says, "so I thought maybe I could contribute knowledge that will help patients."
  
  A life-threatening complication of LAM is pulmonary arterial hypertension (PAH), which also affects people with other lungs diseases including chronic obstructive pulmonary disease (COPD) and cystic fibrosis. In PAH, the pulmonary arteries constrict abnormally, which allows less blood to circulate through the lungs to pick up oxygen. For unknown reasons, exposure to chronic lack of oxygen, called hypoxia, triggers the growth of smooth muscle in the walls of the pulmonary arteries that leads to a thickening of artery walls, high blood pressure and heart failure. "These smooth muscle cells are masters of growth and survival," Dr. Goncharova says. "They grow abnormally and a person ends up with layers and layers of smooth muscle cells, clogging the arteries. A person with PAH can't exercise, their quality of life decreases, and their life expectancy is shortened."
  
  

  "A person with PAH can't exercise, their quality of life decreases and their life expectancy is shortened. I hope that my research will contribute knowledge that will help patients with PAH."

  Dr. Goncharova decided to focus her research on a protein called mammalian target of rapamycin (mTOR), which has been shown to regulate cells growth and proliferation. With the assistance of an American Lung Association Research Award, Dr. Goncharova is investigating 'what activates mTOR and how mTOR acts to promote vascular smooth muscle cell growth. "If we can understand the role mTOR plays in smooth muscle cell growth, it will help us learn how to suppress it," she says. Drugs that inhibit mTOR, including rapamycin, are currently being tested against several forms of cancer. Dr. Goncharova says that if her lab is able to unravel the molecular mechanism by which mTOR promotes smooth muscle growth in the lungs, it could lead to development of new therapies to inhibit smooth muscle cell growth in pulmonary arteries inPAH.

• Alyssa Gregory, PhD
  University Of Pittsburgh, Pittsburgh, PA
  Senior Research Training Fellowship
  Enzyme's Clues to Lung Changes in Idiopathic Pulmonary Fibrosis

  Effective treatments for idiopathic pulmonary fibrosis (IPF), a severe lung disease in which patients develop shortness of breath, decreased exercise capacity, lung scarring (fibrosis) and difficulty with oxygen exchange, are lacking. The researchers will study an enzyme called neutrophil elastase, which is found in high levels in IPF patients. Preliminary evidence suggests that this enzyme may play a key role in the development of IPF. The researchers will examine whether this enzyme can gain entry into cells called fibroblasts that are found in connective tissue, and cause key changes in cellular behavior, which negatively affect IPF patients. They hope to define the way in which neutrophil elastase contributes to IPF. Their research could lead to an important new target for IPF therapy.

• Christoph Grundner, PhD
  Seattle Biomedical Research Institute, Seattle, WA
  Biomedical Research Grant
  Stopping the TB Germ before It Causes Trouble

  Multiple drug-resistant strains of Mycobacterium tuberculosis (MDR-TB) and extensively drugresistant strains (XDR-TB) resistant to virtually every available drug have occurred throughout the world. In countries with poor or failing TB control programs, MDR TB can account for over a quarter of all new TB cases and many high-burden countries do not even test for XDR TB due to lack of resources. Targeting Mtb while it is latent, before it causes active disease, is exceedingly difficult, and new drug targets are urgently needed. The researchers will explore the function of two Mtb enzymes. By knocking out these enzymes genetically and with chemical inhibitors, they will define the role of these enzymes in a model of Mtb growth, latency, reactivation and replication. The enzymes may offer novel drug targets for treating Mtb

• Evelina Guirado, PhD
  Ohio State University, Columbus, OH
  Senior Research Training Fellowship
  Looking for New Targets of Attack on an Old Dangerous Bug

  The researchers will study the interaction between the cell wall of the bacterium that causes TB, Mycobacterium tuberculosis (Mtb), and an immune cell called the macrophage. Normally the macrophage engulfs and destroys bacteria, but Mtb can evade immune defenses and survive to cause infection. The Mtb cell wall contains molecules named lipoglycans decorated with a terminal sugar called mannose. This sugar coating appears to play an important role in the immune system's recognition of and response to the TB bacteria. The researchers will identify key enzymes that are essential building blocks for lipoglycans involved in the addition of mannose. They will alter the levels of genes expressed to determine their impact on the Mtb cell wall mannose production and the interaction of the TB bacteria with macrophages. Information gained from this research should enhance knowledge of TB infection and may help identify new TB therapy targets.

• Ping-Ching Hsu, MS
  Georgetown University, Washington, DC
  Lung Health Dissertation Grant
  Measuring the Impact of Smoking on Lung Cancer Risk

  To better understand the impact of cigarette smoke on lung cancer risk, biomarkers are needed. Biomarkers are molecules found in blood, other body fluids, or tissues that are a sign of a normal or abnormal process, or of a condition or disease. The researchers will identify new biomarkers of lung cancer risk through a powerful method called metabolomics, which measures and analyzes substances in the blood called metabolites. They will investigate whether the number of cigarettes a person smokes per day, how they smoke their cigarettes, and how fast their body metabolizes nicotine will affect how much cancer-causing substances end up in the blood. The information found in the study could be used to evaluate health claims of tobacco products as well as identify former smokers most at risk of developing lung cancer.

• Kelly Hume, DVM
  Cornell University, Ithaca, NY
  Biomedical Research Grant
  Improving Lung Cancer's Responsiveness to Chemotherapy

  Using molecular genetics, the researchers intend to study a novel therapeutic strategy called checkpoint protein impairment, which holds great promise in sensitizing lung cancers to be more responsive to chemotherapy. In cells, certain checkpoints, or control mechanisms, function to protect DNA from damage. The researchers will impair the checkpoint protein Hus1 to see if this stops the progression of lung cancer and if it allows cancer cells to become more sensitized to the chemotherapy drug cisplatin. The findings of this study may be used to develop drugs that target checkpoints involved in lung cancer, which would work in synergy with chemotherapy to improve remission rates for patients with advanced lung cancer.

• Shamsah Kazani, MD
  Brigham And Women's Hospital, Boston, MA
  American Lung Association/Chest Foundation Asthma Clinical Patient Care Research Grant
  Assessing Why Leukotriene-Modifying Drugs Help Only Some With Asthma

  Leukotrienes are chemicals that contribute both to asthmatic inflammation and bronchial muscle contraction. For some people with asthma, leukotriene-modifying drugs lessen symptoms, improve breathing capacity, and reduce the frequency of asthma attacks. But up to half of people with asthma do not respond to leukotriene-modifying drugs. The researchers plan to define the genetic variations in the way leukotrienes affect people with asthma, and the ability of these variations to change people's response to asthma therapy. They will also measure leukotriene levels in exhaled breath samples to determine if these levels can predict the underlying genetic variations. The results of this research will help scientists to predict which patients would benefit from or be resistant to particular asthma therapies, decreasing illness due to use of ineffective medications and/or side effects.

• Mehmet Kesimer, PhD
  

  University Of North Carolina At Chapel Hill, Chapel Hill, NC
  Biomedical Research Grant
  Learning How Tiny Particles Defend the Lung Against Viruses

  The exact role of exosomes, tiny particles secreted by different types of cells, is not known. The researchers have found their presence in lung secretions and propose that they play an important role in defending the lung against viruses, including the influenza virus. Some exosomes have special carbohydrate-rich substances coating their surfaces that may control which viruses they might recognize. The researchers will study the structure of exosomes found in lung secretions, and identify which cells they come from and what kinds of viruses they bind to. They will then explore how they interact with viruses. They hope their research will lead to a deeper knowledge of anti-viral defense mechanisms, which could be used to develop new treatments.

• Shyny Koshy, PhD
  Baylor College Of Medicine, Houston, TX
  Senior Research Training Fellowship
  Targeting Potassium Channels May Lead to Asthma Treatment

  White blood cells called T cells produce inflammatory proteins, and are major contributors to the development of asthma. These T cells have channels on their surface that allows potassium ions to enter and exit the cells. This ion exchange is essential for normal functioning of the T cell. Blocking the potassium channel on these cells will cause them to become inactive, and thus reduce the severity of asthma. The researchers will first determine whether blocking specific potassium channels affects the functions of the T cells from patients with asthma. They will then use a drug that blocks potassium channels to treat asthma in a rat model of chronic asthma. The findings of this study may point to new therapeutic targets for chronic asthma.

• Erin Kross, MD
  University Of Washington, Seattle, WA
  Social Behavioral Research Grant
  Easing Stress of Surrogate Decision-Making in Patients with Acute Lung Injury

  Intensive care unit (ICU) treatment for ALI exposes both patients and their family members to enormous stress. Because the majority of patients in the ICU are not able to participate in medical decisions, family members are often asked to assume the role of surrogate decision-maker, which can be associated with additional stress. The researchers will survey approximately 250 friends and family members of patients who survive ALI. They will examine whether surrogate decision-makers whose preferred role in decision-making does not match their actual role will have more long-term symptoms of depression, anxiety and post-traumatic stress disorder (PTSD). From these interviews, they will identify communication techniques and support mechanisms that surrogate decisionmakers and patients identify as helpful in assessing preferred decision-making roles. The information gained from these interviews will allow the researchers to develop interventions to improve the process of surrogate decision-making for patients with ALI, and eventually help physicians to better support surrogate decision-makers in their role.

• Wladimir Labeikovsky, PhD
  The Rockefeller University, New York, NY
  Senior Research Training Fellowship
  Lung Diseases of Infants and Children Scholar

  Dr. Labeikovsky is using an American Lung Association Senior Research Training Fellowship to understand the details of how a protein that controls the balance of salt in the body called CFTR works, using a protein that shares key features of CFTR, but is much more hardy and stable. "If we can find out this protein's mechanisms and structure, it will tell us a lot about CFTR," he says. Dr. Labeikovsky is now trying to trick this look-alike protein into staying in certain of the poses it adopts during its functional cycle. "Once I do that, I will try to crystallize them to get snapshots of the protein in different stages of its work," he says. "The next step is to start making changes to critical parts of the protein, which will help us fill in the gaps in our knowledge of the detailed mechanism of CFTR."
  
  

  "Results of this work may show which parts of the CFTR protein should be targeted by new cystic fibrosis drugs."

  This knowledge will give scientists a better idea of which parts of the protein should be targeted by new cystic fibrosis drugs. It will also help scientists see how current and potential new treatments work. "Because we don't presently have a good picture of what CFTR looks like, we don't know exactly where drugs are binding the protein and how they work," he says.
  
  This information will allow scientists to design more effective treatments."The American Lung Association grant allowed me to obtain good amounts of the protein, so that we can move into understanding the structure and mechanism of CFTR," Dr. Labeikovsky says. "Without the grant, we would never have come this far."

• Gee Lau, PhD
  University Of Illinois At Urbana-Champaign, Champaign, IL
  Desouza Research Award
  Toxin Could Provide Clues to Bronchiectasis Treatment

  Bronchiectasis is a chronic inflammatory condition that causes airways to widen, weaken and lose elasticity. It is an important component of cystic fibrosis. There is no cure for bronchiectasis, but proper control of infection and other treatments can improve the quality of life for patients. The researchers will examine the disease-causing ability of a toxin called pyocyanin that is produced by the bacteria Pseudomonas aeruginosa, which often grows in mucus of bronchiectasis-affected airways. This toxin causes exaggerated inflammatory response and worsens mucus overproduction. They will study how pyocyanin causes excess mucus production. The results will be useful in developing novel and effective anti-infective therapies to reduce illness and death in patients with this disease.

• Youngnam Lee, PhD
  University of California, San Francisco, CA
  American Lung Association Pneumonia Scholar
  

  Histoplasma capsulatum is a fungus found in the soil, especially in the Ohio and Mississippi River Valley regions in the Midwest and Central and South America. When the soil is disturbed, Parts of the fungus can be inhaled, entering the lungs and infecting lung immune cells called alveolar macrophages.
  
  This inhalation can cause a disease called histoplasmosis in people who have compromised immune systems, such as people with AIDS or cancer, or those undergoing transplantation or chemotherapy. When H. capsulatum infects alveolar macrophages, it divides within the cell and eventually kills the cell. This may lead to the spread of the fungus to new cells and organs if left unchecked.
  
  "This is an understudied fungus," says Youngnam Lee, PhD "Because it doesn't exist throughout the country, it doesn't get a lot of attention. But as more people live longer with diseases such as AIDS and cancer, it is likely to become more common in the future."
  
  Dr. Lee is studying a mutated version of H. capsulatum that can grow within the body's cells, but cannot kill the cells. This H. capsulatum mutant lacks a protein called Cbp1. She is using an American Lung Association Senior Research Training Fellowship to study how Cbp1 kills cells using a mouse model. She hopes to find other proteins or factors with which Cbp1 interacts to induce this killing.
  
  Studying this fungal protein may lead to a better understanding of how H. capsulatum causes disease in people, and provide clues about how it can be targeted for new drug development to combat histoplasmosis.
  
  

  "As more people live longer with diseases such as AIDS and cancer, histoplasmosis is likely to become more common in the future."

  Dr. Lee notes that histoplasmosis is currently treated with antifungal medications, but new treatments are still needed. "Some people with histoplasmosis need long-term antifungal treatment, and we don't know how effective these treatments are over a long period," she says. "We are also concerned because pathogens often become resistant to treatment over time, so we should be developing new types of treatment.

• Philana Lin, MD
  University Of Pittsburgh, Pittsburgh, PA
  Biomedical Research Grant
  Fine-Tuning the Immune System to Help Fight TB

  Previous research has suggested that while a strong immune system response is important in destroying the bacteria, it can also be harmful to the body, making a person feel very sick or even causing death. Immune cells called regulatory T cells are responsible for dampening the immune response, and thus play an important role in balancing the response to infection. The researchers will examine a subset of regulatory T cells that are involved in sending inflammatory cells to the site of infection. Understanding how these cells function in response to M. tuberculosis infection will provide important information on how best to fine-tune the immune system. Results of these studies could lead to improved vaccine and treatment strategies.

• Vincent Lombardi, PhD
  University of Southern California, Los Angeles, CA
  Senior Research Training Fellowship
  Immune Cells, Allergens and Asthma Therapy

  While the cornerstones of asthma therapy—beta2-agonists and inhaled corticosteroids—provide relief of symptoms and some improvements in most patients, there is still no cure for asthma, and symptoms return as soon as therapy is withdrawn. Future therapies might focus on the control of the immune system's responses to allergens, especially in patients whose condition is not adequately controlled by current therapies. The researchers will study how the responsiveness of immune cells called T cell lymphocytes to allergens leads to allergic lung inflammation. These T lymphocytes recognize allergens through cells called dendritic cells, the major regulators of the immune system. The researchers will define which types of dendritic cells in the lung control the body's protective immune system responses against allergens, and will investigate how they work. They hope their research will lead to novel therapies aimed at preventing, Controlling and ultimately curing asthma.

• Quan Lu, PhD
  Harvard University, Boston, MA
  Biomedical Research Grant
  Improving the Effectiveness of Bronchodilators

  Beta-agonists, the most widely used asthma drug, work on the beta2-adrenergic receptor (b2AR) in the lung to relax smooth muscles and reduce constriction in the airways. However, over time, beta-agonists become less effective, mainly because continued stimulation of receptors by beta-agonists reduces the amount of functional receptors in the lung. Using a powerful genetic tool developed in their lab, the researchers hope to identify critical genes that play an important role in this degradation of the beta2-adrenergic receptor and understand their roles in the process. The research may provide new ways to improve beta-agonist-based asthma therapies. 10 www.

• Nilam Mangalmurti, MD
  University Of Pennsylvania, Philadelphia, PA
  Biomedical Research Grant
  Preventing Acute Lung Injury After Transfusions

  Red blood cell (RBC) transfusions are routinely given in the intensive care unit (ICU). They have been associated with the development of acute lung injury (life-threatening respiratory failure) and increased death rates in the critically ill. Yet the reasons for this remain unknown. The researchers hope to define the way in which RBC transfusions worsen lung injury in the critically ill. They will examine whether transfusion of stored RBCs sensitizes cells in the blood vessels of the lung to subsequent injury. They will specifically look at whether RBCs increase production of a protein called RAGE, which promotes inflammation. Understanding how RBC transfusions increase RAGE and worsen acute lung injury may lead to strategies to prevent lung injury associated with transfusions. Knowledge derived from these studies may lead to specific therapies such as blocking activation of RAGE in cells of the blood vessels of the lung, or modifying storage methods to prevent the development of acute lung injury associated with transfusions.

• Joan Mangan, PhD, MST
  University Of Florida, Gainesville, FL
  Social Behavioral Research Grant
  Developing Myth-Busting Messages About a Tuberculosis Vaccine

  Stigma and misperceptions surrounding TB have been associated with patients delaying seeking care; failing to undergo or complete diagnostic testing; rejecting physicians' diagnoses, and failing to complete treatment. The problem is compounded by the fact that in low- to middle-income countries, (BCG) vaccine is given to reduce the risk of developing more severe forms of TB among infants and children who become infected with TB germs. The BCG vaccine does not provide lifetime protection against TB; yet community members tend to believe the vaccine protects a person from becoming sick with TB throughout their life and a positive TB test is due to the vaccine. The researchers will develop culturally competent educational messages that lessen the confusion individuals experience about the vaccination and their need for testing and treatment of TB; and test the impact of these messages on foreign-born Hispanic persons' understanding of this risk and intended decisions if testing and treatment is recommended to them in the future.

• Alison Mcleish, PhD
  University Of Cincinnati, Cincinnati, OH
  Social Behavioral Research Grant
  Helping People with Asthma to Quit Smoking

  Asthmatics who smoke have more asthma attacks, a harder time controlling their asthma with medications, and greater impairments in overall daily functioning and quality of life. Many of these problems can be improved by quitting smoking yet there is currently little information about smoking cessation among people with asthma. The researchers will examine differences in smoking cessation rates between smokers with and without asthma, and identify factors that contribute to poor smoking cessation success rates among smokers with asthma. The study will follow 96 smokers (half of whom have asthma) using Palm Pilots for three months after they try to quit smoking on their own. At various times during the study, Participants will report whether or not they are smoking, their withdrawal symptoms, and their current emotional status. The project will hopefully allow the researchers to develop specialized smoking cessation programs for people with asthma.

• Charlotte Mitchell, PhD
  Yale University, New Haven, CT
  Senior Research Training Fellowship
  Understanding the Airway Epithelium… The Lungs First Line of Defense

  Epithelial cells line the airway, creating a surface called the epithelium. The epithelium is important for protecting and regulating immune responses in the lung. Interferon-gamma (IFN-g) is a protein chemical messenger that is important for defense during disease, but its effect on the epithelium is not known. The researchers have developed a mouse in which the receptor for IFN-g is absent from all cells except airway epithelial cells, which allows only the epithelium to respond to IFN-g. Using this mouse, the researchers can identify how the airway epithelium responds to IFN-g to affect disease. Infection with Mycobacterium tuberculosis and pulmonary fibrosis are serious diseases of the lung, and IFN-g is an important factor in both these diseases. The researchers hope to clarify the role of the IFN-g responses by the airway epithelium in mouse models of mycobacterial infection and pulmonary fibrosis. These studies may identify novel pathways that can be used for future treatment of these disease

• Vera Moiseenkova-Bell, PhD
  Case Western Reserve University, Cleveland, OH
  Biomedical Research Grant
  Finding a New Pathway for Asthma Triggers Could Lead to New Therapies

  The researchers are studying a newly discovered protein called TRPA1, a so-called "irritant receptor" that detects irritation in the airways and is key in the development of airway inflammation. They will develop an extensive understanding of the structure and function of TRPA1. By studying the three-dimensional structure of this protein, they hope to find out how irritants such as smoke, vehicle exhaust, and air pollution trigger asthma. This knowledge could lay the groundwork for future studies that could ultimately help in designing anti-inflammatory medication that could significantly improve the lives of asthma patients.

• Kari Christine Nadeau, MD, PhD
  Stanford University, Stanford, CA
  American Lung Association/Aaaai Allergic Respiratory Disease Award
  Defining the Role of Ambient Air Pollution in Children's Asthma

  Studies have demonstrated that short-term and long-term exposure to ambient air pollution leads to detrimental changes in the lung and blood. Children have been found to be at the highest risk of the negative health effects of ambient air pollution. The researchers will study whether children with increased chronic exposure to air pollution have increased asthma in two California communities, Fresno and Stanford. Fresno, the third most polluted city in the United States, has been shown to have asthma prevalence five times higher than the nationwide average. The study will include analysis of individual air pollution exposure data, health questionnaires and lung function tests. The researchers hope to learn whether specific exposures, the health outcomes of individual children, and changes in the immune system are correlated.

• Fumihiko Namba, PhD, MD
  Children's Hospital Of Philadelphia, Philadelphia, PA
  Senior Research Training Fellowship
  Protecting New Lungs from Damage by Oxygen

  Most newborn babies who are born prematurely or who experience respiratory problems shortly after birth need supplemental oxygen. The exposure to excess oxygen, called hyperoxia, can cause lung injury and abnormal development of lung tissue. An enzyme called heme oxygenase-1 (HO-1) has been shown to protect against cell death. Although HO-1 is normally found in the cell's cytoplasm, it migrates to the nucleus in the lungs of newborn mice exposed to excess oxygen and is likely to play a role in DNA repair. The researchers will study whether HO-1 protects against hyperoxia in the newborn lung by examining the effects of HO-1, found in the nucleus of lung cells, on DNA damage and repair in mice genetically engineered to produce excessive amounts of HO-1. After the mice are exposed to excess oxygen for 72 hours, their lungs will be evaluated, with special attention given to enzyme activity, lung development and DNA damage. Understanding HO-1's function and its role in hyperoxia in the newborn lung may lead to treatments to protect newborn babies against lung damage caused by hyperoxia.

• Katsuhide Okunishi, MD, PhD
  University Of Michigan, Ann Arbor, MI
  Senior Research Training Fellowship
  Understanding Why Some People Develop Excessive Lung Scarring

  Cells called fibroblasts are now recognized as important in the development of lung fibrosis. A substance produced in the lung called prostaglandin E2 (PGE2) suppresses virtually all the functions of fibroblasts in normal lungs and could be an attractive candidate for an anti-fibrotic drug. But the researchers have found that fibroblasts from the lungs of some IPF patients are resistant to the suppressive action of PGE2. They will study how PGE2 works inside normal fibroblasts, and why it does not work in fibroblasts of patients with IPF. In particular, they will test the possibility that a process called plasminogen activation may be able to restore PGE2 effectiveness in IPF fibroblasts. The research may lay a foundation for the development of a new possible treatment: combined administration of PGE2 plus agents such as urokinase that increase plasminogen activation.

• Jose Perez-Zoghbi, PhD
  Texas Tech University, Lubbock, TX
  Biomedical Research Grant
  New Clues to Airway Narrowing in Obstructive Lung Disease

  A characteristic of asthma and other lung diseases such as chronic obstructive pulmonary disease (COPD) is the excessive narrowing of the airways in response to stimuli. The narrowing of the airways is produced by a contraction in the muscle that surrounds the airways. Chemical signals within the muscle regulate its contraction. The researchers will investigate how these signals regulate the contraction of the muscle and how they are affected during disease. They will use a mouse model of asthma that does not respond to current drug treatments. They will compare the response of stimuli in the airways of these mice to the response in airways of healthy mice. This knowledge can be used to help in the design of new treatments of obstructive lung disease.

• Daniela Petrusca, PhD
  Indiana University, Indianapolis, IN
  Biomedical Research Grant
  Cigarette Smoke's Role in Emphysema

  The disruption of the balance between death and replenishment of structural cells in the lung is considered a major mechanism of destruction of lung tissue in response to cigarette smoke. The clearance of dead cells is an important process that protects tissues from the toxic contents of dying cells, which may cause damage to the surrounding tissue and may produce inflammation. The lungs possess specialized immune cells called macrophages that are responsible for engulfing the dying cells. Cigarette smoke exposure, however, impairs this function. Cigarette smoke also introduces in these cells a special state of "self protection" that when functioning properly, helps the cell live in harsh conditions. But chronic cigarette smoke exposure alters this self-protection mechanism. The researchers will study the mechanism that links the impairment caused by cigarette smoking in the cleaning up of dying cells to the alterations in the cells' self-protection state. The results may lead to potential targets of emphysema treatment.

• Einat Rabinovich, MD
  University Of Pittsburgh, Pittsburgh, PA
  Senior Research Training Fellowship
  Molecular Strategies to Treat Excessive Lung Scarring

  Studies have shown that even decades after an initial environmental exposure, changes in the lung continue in people with idiopathic pulmonary fibrosis (IPF). The researchers will use technologies that allow genetic profiling to study the role of genetic changes in the abnormal IPF lung. Their focus will be the role of a process called DNA methylation in the development of IPF. DNA methylation is a naturally occurring chemical modification of DNA often caused by environmental and occupational factors, which can induce changes in the regulation of cells. Gaining a better understanding of DNA methylation's role in IPF could lead to the discovery of new molecular targets for therapy, better use of available drugs, and improvements in diagnosis and management of IPF.

• Arne Rietsch, PhD
  Case Western Reserve University, Cleveland, OH
  Biomedical Research Grant
  Unraveling Workings of Bacteria that Cause Lung Infections in CF Patients

  Pseudomonas aeruginosa is one of the most common bacteria that infect critically ill patients and cause ventilator-associated pneumonia. It is also the number one pathogen responsible for the chronic lung infections in patients with cystic fibrosis and is responsible for the majority of the illness and death in this patient group. One of the problems with P. aeruginosa is that infections are difficult to treat due to the high antibiotic resistance of the organism. New targets for treatment are sorely needed. The researchers are studying one of the main systems that P. aeruginosa uses to cause disease, a syringe-like appendage that allows the bacterium to directly inject toxins into host cells. They hope to better understand how these molecular syringes function, information that potentially could be used to treat P. aeruginosa infections.

• Masahiro Sakagami, PhD
  Virginia Commonwealth University, Richmond, VA
  Biomedical Research Grant
  Triple-Action Potential Treatment for Emphysema

  Little is known about how to effectively control the emphysema. As a result, its treatment is limited to managing symptoms using bronchodilators and inhaled steroids, with marginal success and no cures. The researchers will test the treatment potential of unique substances called cinnamic acid-based oligomers using a rat model of emphysema. They will study how large a dose is needed to be effective, and how long the treatment lasts. If proven effective, this inhaled treatment could be a brand-new class of drug that aims to simultaneously inhibit three processes in the lung that are thought to be critically involved in the development of emphysema. The researchers will investigate whether by attacking emphysema through three mechanisms, it will have more success than current treatments, which treat one mechanism at a time (such as inflammation or airway constriction).

• Kaori Sakamoto, PhD, DVM
  University of Georgia, Athens, GA
  American Lung Association Tuberculosis Scholar
  American Lung Association Tuberculosis Scholar

  When a person inhales a germ, frontline immune system cells called alveolar macrophages normally digest it, protecting the lungs. But that does not happen when a person inhales Mycobacterium tuberculosis (Mtb), the germ that causes TB. This allows Mtb to stay alive in the lung and cause infection.

  "Much of the basic science of TB research is centered around how Mtb manages to evade degradation within macrophages," says Kaori Sakamoto, PhD, DVM. "Some of the mechanisms of this process have been determined, but there are still many unanswered questions."

  "It was never known that MARCO played a role in TB before. That opened up a new avenue for us which was very exciting."

  With a Biomedical Research Grant from the American Lung Association, Dr. Sakamoto is studying a receptor called MARCO that is found on the macrophage surface, to understand its role in tuberculosis infection.

  In an earlier study, Dr. Sakamoto collaborated on a study that screened people with active TB and the uninfected people who lived with them. The researchers noticed that a variation in the MARCO gene was more often present in people with active TB. "It was never known that MARCO played a role in TB before," she says. "That opened up a new avenue for us, which was very exciting." In another study, she found that MARCO binds to a component of the cell wall of Mtb that is important in TB.

  Dr. Sakamoto and her collaborator, Dr. Dawn Bowdish of McMaster University, found that a genetic variation in the MARCO gene causes a shortened version of MARCO, called MARCOII, which is associated with susceptibility to TB. Dr. Sakamoto will take cells that don't normally produce MARCO, and inject them with genetic material to force them to produce either MARCO or MARCOII. She will then compare the two versions to see whether there are differences in binding, uptake, or macrophage responses to Mtb. "We hope this will help us understand why the shortened version of MARCO is associated with susceptibility to TB at the cellular and molecular levels," she says. "If we can figure out what role MARCO plays in susceptibility to TB, there may be a potential to use this information to prevent TB infection. We also may be able to target MARCO to treat infection," she says.

  She notes that it is possible that MARCOII may play a role in other lung diseases in addition to TB. "Our research may elucidate what role MARCO could be playing in these other diseases," she says.

• Nathan Sandbo, MD
  University Of Wisconsin, Madison, WI
  Dalsemer Research Grant
  Controlling "Overactive" Scar Forming Cells in the Lungs

  Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease, characterized by lung scarring. Given the dire prognosis of idiopathic pulmonary fibrosis (IPF) and lack of treatment options, novel targets for drug therapy are needed to stop the scarring process in the lungs. The researchers are studying the process within lung cells called fibroblasts that lead them to cause scarring in the lungs. They are focusing on a substance called Transforming Growth Factor-beta, which starts a cascade of signals within the cells that leads to scarring. They hope to identify new signaling molecules and events that are involved in this process, which may provide important new targets for drugs that might halt the inexorable progression of IPF.

• Debasish Sen, PhD
  University Of California, San Francisco, San Francisco, CA
  Senior Research Training Fellowship
  Novel Imaging Technique Answers Questions About Allergen-Induced Asthma

  Although there are many asthma treatments, new therapies are needed to alter the long-term sensitivity of the immune system to environmental allergens. The researchers will directly observe asthmatic lungs' inflammatory response to allergens. They will use a novel technique called two-photon imaging that allows visualization of single cells, to determine how and where in the lungs cells called antigen-presenting cells assist in aggravating inflammatory responses to asthma. They hope to develop strategies for targeted inhibition of these asthma-aggravating cells, and initiate research toward the development of effective anti-inflammatory long-term asthma therapies.

• Emelyn Helen Shroff, PhD
  Stanford University, Stanford, CA
  Senior Research Training Fellowship
  Stem Cells May Hold The Key to Turning Off Cancer Cells

  The researchers are studying the role of a cancer gene, or oncogene, called MYC, that also regulates stem cell properties. Oncogenes turn normal cells into cancer cells. The researchers are using a mouse model to regulate the production of these oncogenes. By switching off these oncogenes through genetic manipulation, tumors usually regress. But they have identified that in lung cancer caused by MYC, the tumors do not regress when MYC is switched off. Since MYC is also important for regulating self-renewal, the researchers will assess whether lung tumors that do not rely on MYC to grow instead rely on the emergence of a population of stem-cell like cells with self-renewal properties. The researchers hope to identify this population of cells. They will also look for other specific genes that also promote self-renewal and see whether turning off these genes will eliminate their self-renewal properties. Understanding these processes could have a tremendous impact on future development of drugs targeting lung cancer.

• Umapathy Nagavedi Siddaramappa, PhD
  Medical College Of Georgia, Augusta, GA
  Biomedical Research Grant
  Enzyme Could Help Protect Lungs Against Damage from Injury

  The severe form of acute lung injury (ALI), called acute respiratory distress syndrome (ARDS) is associated with high death rate (30-50%) affecting all or most of both lungs that occur as a result of illness, injury or trauma. The injured lung becomes significantly inflamed, resulting in damage to the endothelium, the layer of cells lining the inner surface of blood vessels which provides a selective barrier between blood and the surrounding tissue. These changes in the endothelium make it more permeable, allowing a dangerous buildup of fluid in the air sacs of the lungs. The researchers are studying the dysfunction of the endothelial barrier caused by injury that makes it more porous. They are looking at a molecule called b-NAD that protects and repairs the endothelium. A better understanding of the way in which b-NAD works could lead to treatments for this devastating disease where there is no treatment presently available except putting the patient on a ventilator.

• Christopher George Slatore, MD
  Oregon Health & Science University, Portland, OR
  Social Behavioral Research Grant
  Examining the Role of Depression in Lung Cancer Care

  Many people with lung cancer also suffer from depression, an often overlooked disease. Since depression can be treated with well-established therapies, identifying its role in lung cancer care could improve quality of life and decrease illness among the large number of patients who suffer from depression and lung cancer. The researchers will launch a series of four studies to evaluate depression among lung cancer patients enrolled in a study called Cancer Care Outcomes Research and Surveillance Consortium (CanCORS). They will examine the association between depression and outcomes including timeliness of care (the time from first symptoms of lung cancer to treatment), receipt of recommended therapies, and receipt of smoking cessation interventions. This research could help further cement recommendations to screen for depression as well as offer treatment incentives to improve outcomes for the likely large number of lung cancer patients with depression.

• Genee Smith, MSPH
  University Of North Carolina, Chapel Hill, NC
  Lung Health Dissertation Grant, American Lung Association Behavioral Risk Factor Scholar
  Does Air Pollution Increase the Risk of Developing TB?

  While some studies in mice have suggested a possible link between tuberculosis and air pollution, this question has not been studied on a large scale in humans. Previous research suggests that air pollution, by increasing inflammation in the lungs and decreasing the immune system's response, may increase the risk of developing TB. The link between tuberculosis and smoking is also unclear, with some research showing an association and some not finding a connection.
  
  

  "The results of the study could have global implications and could not have been done without American Lung Association support."

  Genee Smith will use an American Lung Association Lung Health Dissertation Award to examine both questions. She will link two major sources of information: electronic medical records from the Kaiser Permanente patient database and air pollution data from the California Air Resources Board (CARB). The study will include records of 3,000 adults with active TB and 6,000 healthy adults without a history of TB, all of whom live in California.
  
  The medical records will tell Ms. Smith which patients have a history of smoking. They will also contain patients' addresses and how long they have lived at that location. She will compare those records with the CARB data to estimate individual-level exposures and their relationship to TB. She will also examine whether the association between air pollution and TB is stronger among smokers than non-smokers.
  
  "California is a natural place to conduct this study, because the state has excellent air pollution data, and Kaiser Permanente, which is based in California, has a huge number of electronic medical records," Ms. Smith says. She is working with Kaiser to develop a model that will take into account where a person lives, and link that information to air pollution data starting 24 months before they were diagnosed with TB. The results of the study could have global implications, since many developing countries have both high rates of TB and severe air pollution, she says.
  
  "Because Kaiser has more than three million people in their database, I would not be able to do this scale of epidemiologic study without the funding provided by the American Lung Association," Ms. Smith says.

• Christina Stallings, PhD
  Washington University, St. Louis, MO
  Biomedical Research Grant
  How Protein Helps TB Bacteria Stand Up to Immune System's Assaults

  During infection, mycobacteria must withstand an arsenal of assaults by the body's immune system. The researchers have identified a protein called mycobacterial CarD, which regulates the response of M. tuberculosis to these assaults, and is essential for acute and persistent infection. They will investigate how CarD functions. This information could be used to design screens for potential drugs that target CarD, which may lead to development of new agents to treat TB.

• Kymberle Sterling, DrPH MPH
  George State University, Atlanta, GA
  American Lung Association Behavioral Risk Factor Scholar
  American Lung Association Risk Factor Scholar

  Waterpipe, or hookah, smoking, has become increasingly popular among young people. In 2010, the nationwide Monitoring the Future study found that 17 percent of 12th graders said they had used hookahs in the past year. The hookah heats specially-made tobacco, which comes in a variety of sweet flavors, and then passes the smoke through a bowl of water. The smoker then draws this tobacco smoke through a mouthpiece connected to the pipe by a rubber hose. Because of the way a hookah is used, smokers may absorb higher concentrations of the same toxins found in cigarette smoke. In fact, a person smoking a hookah for one hour inhales 100 to 200 times the volume of smoke inhaled from one cigarette. Dr. Kymberle Sterling is using an American Lung Association Social Behavioral Research Grant to study college students' perceptions of hookah smoking and the effect of hookah advertising on those perceptions. She is also exploring the prevalence of hookah use in this group.
  
  People who use hookahs are also at risk for the same diseases caused by cigarettes, including cancer of the lung, mouth and esophagus. "Some people incorrectly believe that the water filtration process in hookah smoking makes it less harmful, and that toxins are removed as the smoke passes through the water," she says. "Because the sweetened tobacco used is less irritating and provides a more pleasant smoking experience than cigarettes that adds to the perception that it's safer to smoke."
  
  

  "Unbeknownst to most of the general public, hookah smoking carries many of the same health risks as cigarettes."

  Dr. Sterling's two-year study will be broken into three phases. In the first phase, she will analyze ads about hookah use to see what types of messages are being promoted; followed by holding eight focus groups of six to eight students to decipher beliefs about hookah use and advertising. For those who are hookah smokers, she will ask why they started using hookahs, why they continue to use them and if they use other tobacco products, to see if there appears to be a relationship between hookah smoking and use of other tobacco products. In the final phase of the project, Dr. Sterling will use the information gained to develop survey measures to help estimate the prevalence of hookah use, attitudes and beliefs about hookah smoking, and college students' exposure to hookah ads and promotions.
  
  "We hope results from this study will inform the public health community about the prevalence of hookah use among college students, and the impact hookah ads have on rates of use," she says. "This information can be used to develop evidence-based public health interventions to reduce hookah use among young people."

• Melissa Suter, PhD
  Massachusetts General Hospital, Boston, MA
  Biomedical Research Grant
  'Smart Needle' Could Increase Accuracy of Early Lung Cancer Diagnosis

  The survival of patients with lung cancer is directly related to the stage at which the cancer is detected. However, screening for lung cancer is currently not recommended. This is partly due to difficulties in obtaining an accurate diagnosis following the identification of possible early cancers on chest X-ray or CT screening techniques. Many of the detected lesions, or nodules, are small. Accurately locating them and taking a tissue sample for diagnosis is difficult, even when performed with advanced image guidance techniques. The researchers plan to develop a new optical imaging tool that will increase the number of these small nodules that can be located and biopsied. The optical imaging device generates microscopic images of the lung tissue and can be miniaturized to fit within a standard needle commonly used to acquire lung tissue specimens. Using this imaging device, the researchers will confirm whether the needle is correctly placed within the target lung nodule prior to obtaining tissue specimens. Use of the 'smart needle' could lead to a reduction in potentially fatal delays in diagnosis and subsequent treatment in patients who may be falsely diagnosed as negative for lung cancer. This tool may also result in a reduction of unnecessary high-risk surgical procedures for the removal of nodules that currently cannot be biopsied.

• Roger Tsien, PhD
  University of California, San Diego, CA
  Senior Investigator Award
  Senior Investigator Award

  Roger Tsien, PhD, is a Nobel Prize winner in chemistry who is using his expertise to bring a new perspective to the study of asthma. Dr. Tsien is the first recipient of the American Lung Association/American Asthma Foundation Senior Investigator Award, given to a non-pulmonologist conducting novel and innovative research on asthma.
  
  

  "I am hopeful we can make a scientific discovery that could help develop a better understanding of a disease I have experienced personally."

  Dr. Tsien will be focusing on the work of proteases, which are ubiquitous enzymes involved in many biological processes including the inflammation that underlies asthma. Little is known about precisely when and where different proteases become active in asthma. Dr. Tsien, Professor of Pharmacology and Chemistry & Biochemistry at the University of California, San Diego, will use an imaging technique already developed for cancer and apply it to proteases to better understand how they are involved in asthma.
  
  "We realized this imaging technique had many potential applications to other diseases, including atherosclerosis, or hardening of the arteries, which involves immune cells that are attacking blood vessels," Dr. Tsien says. "It will also apply to asthma, a disease in which immune cells attack lung cells." The development of agents to target these enzymes for the treatment of asthma requires knowledge of exactly where, when and how they act in the lung. Dr. Tsien's research, which will be conducted in an animal model, aims to answer these questions. Eventually, Dr. Tsien says the findings from the study could be applied to human patients for diagnosis and potentially for the evaluation of new treatments for asthma.
  
  Dr. Tsien is eager to be studying asthma, which he has had since childhood on the East Coast. "I suffered from allergic asthma as a child," he says. "Since growing up and moving to California I don't suffer from allergy-induced asthma anymore, but I can still get exercise-induced asthma, and I carry an inhaler with me at all times. I am hopeful we can make a scientific discovery that could help develop a better understanding of a disease I have experienced personally." Dr. Tsien was a co-recipient of the 2008 Nobel Prize in chemistry, with Osamu Shimomura and Martin Chalfie, for the discovery and development of the green fluorescent protein, GFP. First observed in jellyfish, GFP has been used to develop ways to watch processes that were previously invisible, such as the development of nerve cells in the brain or how cancer cells spread. "That work, like my asthma research, was also related to imaging biological processes," he says. The American Lung Association/American Asthma Foundation Senior Investigator Award is a three-year award valued at $250,000 per year.

• Hoshang Unwalla, PhD
  University Of Miami, Miami, FL
  Biomedical Research Grant
  Improving Effectiveness of COPD Drugs

  Acute flare-ups of COPD and asthma are treated with inhaled bronchodilators, which are available in an aerosolized form for inhalation. When inhaled, these drugs have to get through airway cells called epithelial cells in order to reach smooth muscle cells, which contract in people with obstructive lung disease. The bronchodilators cause the smooth muscle cells to relax, thus widening the airways. The researchers have shown that one of the most commonly used bronchodilator drugs, albuterol, can enhance its own transport across epithelial cells to elicit a rapid onset of action on smooth muscle cells. They will study the basis of this action, and determine if other inhaled bronchodilators demonstrate a similar ability. The information gained from this study could be used to devise better formulations and combinations of bronchodilators for effective treatment of COPD or devise alternative strategies in airway diseases where this pathway is afflicted.

• David Verhoeven, PhD
  Rochester General Hospital, Rochester, NY
  Biomedical Research Grant
  Why Does Influenza Cause More Severe Illness in Young Children?

  Children are particularly prone to and suffer from high rates of illness throughout the course of influenza infection than adults. The researchers will study possible mechanisms that account for this discrepancy. Using a mouse model, the researchers will compare the differences in the level of illness, as well as, the amount of inflammation and lung damage during influenza infection between infants and adults. Preliminary research suggests that the lungs of young children do not respond like those of adults during influenza infection. By further exploring the differences between infant and adult lung responses to infection, the researchers hope to gain a better understanding of what causes more severe illness in children infected with the influenza virus. These mechanisms might provide potential therapeutic or vaccination targets to limit or prevent the amount of lung tissue damage during infection of children.

• Yui-Hsi Wang, PhD
  Cincinnati Children's Hospital Medical Center, Cincinnati, OH
  American Lung Association/Aaaai Allergic Respiratory Disease Award
  Unique Type of White Blood Cell May Provide Clues to Allergic Asthma

  A type of long-living white blood cell called memory type-2 T-helper cells (Th2) is believed to be the principal cell type that causes recurrent symptoms in patients with allergic asthma. These memory Th2 cells can produce substances called Th2 cytokines that trigger a potent allergic immune response. Another immune factor, called interleukin-17, has an important role in triggering airway inflammation. The researchers have discovered a unique type of Th2 cell that can produce both Th2 cytokines and interleukin-17, thereby inducing a potent allergic response as well as airway inflammation. They will study the factors that regulate the production of these unique Th2 cells and identify their roles in driving the severity of chronic allergic asthma. The study will provide new insights into the nature of long-lived Th2 cells and may pave the way for improved diagnosis and treatment of allergic disease.

• James Webb, DPhil
  University Of Pennsylvania, Philadelphia, PA
  Senior Research Training Fellowship
  Disabling Proteins that Help Lung Cancer Cells Get Oxygen

  
  A low oxygen level, or hypoxia, is common in lung tumors, because of rapidly dividing cells that have circumvented the body's usual checkpoints and are dividing out of control. They divide so fast they overtake the ability of the blood to deliver oxygen. Because oxygen is critical for normal energy production in cells, organisms have evolved a series of responses designed to deal with hypoxia. The main regulators of these responses are a group of proteins known as hypoxia-inducible factors (HIFs), which have been found in high levels in many lung cancer tumors. The researchers will study how inhibiting HIFs can affect lung cancer progression. Using a mouse model of lung cancer, they will delete an essential protein that will disable the ability of HIFs to send cellular signals. Lung tumors of these mice will be compared with the tumors of mice without the deleted protein. This research will help to define the role of HIF in lung cancer, and aid in the development of targeted therapies.

• Kwok-Kin Wong, MD, PhD
  Dana-Farber Cancer Institute, Boston, MA
  Lung Cancer Discovery Award
  Can the Immune System Control the Spread of Cancer?

  
  To improve the long-term survival of patients with lung cancer, it is critical to develop a better understanding of the processes involved in lung cancer progression and metastasis. Until recently, there has not been a good model system to study lung cancer metastasis in a living organism. The researchers will use a mouse model they have generated that spontaneously develops lung cancer which spreads to distant organs, to genetically dissect the pathways that are involved in lung cancer progression and metastasis. They will also examine the role of the immune system in the development and progression of lung cancer. This research may identify crucial new targets involved in lung cancer progression and metastasis for possible new treatments.

• Kazuko Yamamoto, MD, PhD
  Boston University, Boston, MA
  Senior Research Training Fellowship
  Fine Tuning the Lungs Response to Pneumonia Causing Bacteria

  
  During a lung infection such as pneumonia, white blood cells called neutrophils are recruited from the blood into the air spaces of the lungs, where they are essential for clearing bacteria. But excess recruitment of these cells may cause acute lung injury. The coordination of this delicate inflammatory process requires a family of cell-signaling proteins called cytokines that regulate and maintain immune system activity. Creation of cytokines is initiated in large part by signaling from a protein called NF-kappaB. The researchers will study a specific type of NF-kappaB, to determine their role in the immune system's response to pneumonia. The results of the study will help to identify specific aspects of the immune system that can be targeted in order to decrease illness and death caused by pneumonia.

• Cuneyt Yilmaz, PhD
  Ut Southwestern Medical Center, Dallas, TX
  Biomedical Research Grant
  How Does the Obesity Epidemic Fuel the Obstructive Lung Disease Epidemic?

  Both diabetes and obesity can cause low-grade inflammation in the lung, restrict the volume of air the lung can take in, and cause abnormal breathing responses to exercise stress. This reduced lung function may contribute to serious heart and lung problems in older people. There is a need to understand how and why obesity and diabetes affect lung structure and function, and whether their adverse effects on lung health can be reversed with treatment. The researchers will use a novel technique to measure heart and lung function in a rodent model of genetic obesity-associated diabetes, which will help them better understand the loss of lung function related to this condition.

• Zhenxiong Zhang, MD, PhD
  Lovelace Respiratory Research Institute, Albuquerque, NM
  Biomedical Research Grant
  Preventing Deadly Respiratory Problems Caused by Opioids in COPD Patients

  Rapid shallow breathing (RSB), commonly occurs in patients with lung disorders such as chronic obstructive pulmonary disease (COPD). Compared to healthy people, Patients with RSB are more prone to suffer respiratory depression and respiratory failure when they are given opioid painkillers such as fentanyl. This life-threatening impact on breathing has markedly limited the use of these painkillers in patients with pulmonary disease such as COPD. To date, the reason for this predisposition to suffer respiratory problems induced by these painkillers is not clear. RSB is primarily generated by the stimulation of small nerve fibers in the lungs called pulmonary C-fibers (PCFs). PCFs can be stimulated when pulmonary inflammation, Congestion, infection, and accumulation of excessive fluid, or edema—characteristics of COPD—are present. The researchers have found that an intravenous injection of fentanyl switched RSB to a long-lasting breathing stoppage, or apnea, of up to five seconds in anesthetized rats. The researchers wish to understand how fentanyl makes this switch. The study may lead to discoveries that could be used to prevent and reduce the incidence of life-threatening respiratory depression by opioids, especially in patients with lung diseases.

• Nives Zimmermann, MD
  Cincinnati Children's Hospital Medical Center, Cincinnati, OH
  American Lung Association/Aaaai Allergic Respiratory Disease Award
  Do Asthma Patients Need Acid Blockers for Their Airways?

  Clinical studies have shown that the airways of people with asthma become acidic, and that buffering airway acid improves symptoms. However, more information is needed about acid in the airways of people with asthma. Using a mouse model, the researchers will explore the role and mechanism of airway acidification in asthma. The researchers have already found that mouse airways are acidified when they are inflamed, which occurs in asthma. The study findings could have considerable implications for the development of therapies that target airway acidification in asthma and other diseases that involve inflammation of the airways. For

Completed Studies

• Alan P. Fields, PhD
  Mayo Clinic Jacksonville
  American Lung Association/LUNGevity Foundation Lung Cancer Discovery Award 2006-2008
  Rheumatoid Arthritis Drug Studied for Non-Small Cell Lung Cancer

  Dr. Fields has discovered that a drug currently being used to treat rheumatoid arthritis shows promise in treating some types of lung cancer. The drug, called aurothiomalate (ATM), is a targeted therapy, meaning it doesn't kill both cancer and normal cells, the way many chemotherapy drugs do, which can lead to severe side effects. Rather, ATM targets a gene called protein kinase Ciota (PKCi) that is essential for the development of lung cancer. Blocking PKCi activity blocks lung cancer cell growth, suggesting that a drug that blocks PKCi activity might also be an effective treatment against lung cancer.

  With the Lung Cancer Discovery Award, Dr. Fields found that the majority of lung cancer cells are sensitive to ATM, and that those lung cancer cells that have very high levels of PKCi are the most sensitive to ATM. These results suggest that lung cancer patients whose tumors have high PKCi levels are likely to respond to ATM therapy. Building on the data that Dr. Fields gathered through his American Lung Association grant, he and his colleagues have conducted a Phase I clinical trial of ATM in lung cancer patients, to assess the safety and optimal dosing of the drug for lung cancer treatment. His results show that ATM is well-tolerated. He has now started several phaseI/II trials to assess the effectiveness of the drug in combination with another targeted agent as a treatment for lung cancer. Clinical trials are also ongoing to explore the potential of ATM in the treatment

• Christy Houle, PhD, MPH
  University of Michigan
  Lung Health Dissertation 2007-2008
  Evaluating How Teens and Caregivers Answer Asthma Questions Differently

  Management of asthma by adolescents, Particularly in urban minority populations, is not well understood. Selfreported asthma information from patients and families is important to doctors who treat patients and researchers who study the disease. Emerging evidence suggests that adolescents and caregivers give different responses when asked about the teen's asthma, yet there are many unanswered questions about why this is so. This lack of knowledge makes it difficult to develop strategies that may increase the usefulness of self-reported asthma information.
  
  Dr. Houle studied the comprehensibility and relevancy of the Asthma Control Test, a widely used questionnaire designed to identify poorly controlled asthma, in 35 pairs of African-American adolescents and their caregivers. The teenagers and their caregivers also participated in in-depth interviews. Dr. Houle demonstrated that the responses of adolescents and caregivers often do not agree, especially regarding questions about asthma symptoms. Differences in reporting are associated with personal and clinical characteristics of the respondent.
  
  She found that the self-reports of adolescents may be the best source of information regarding asthma symptoms and functioning, while caregivers are likely better positioned to report on an adolescent's medical history. Adolescents and their caregivers appear to provide similar information about health care use. Her results suggest that caregiver and adolescent descriptions of "wheeze" and "asthma control" are different from each other, and both may be different from the clinical definition of the terms. She also found many teenagers reported not being entirely truthful when telling their caregivers about their asthma symptoms and functioning.
  
  Her findings highlight the importance of cultural competence in the ways in which questions about asthma are framed and interpreted in clinical and research settings. They suggest that changes to commonly used questions may result in answers of greater validity and reliability.
  
  Dr. Houle's work funded by the American Lung Association has since led to several asthma-related collaborations with colleagues at the University of Michigan. She now works for a global scientific and medical affairs organization, where she develops and evaluates the performance properties of instruments to assess patient-reported outcomes, Particularly in the respiratory field.

• Jonathan C. Jun, MD
  Johns Hopkins University
  American Lung Association/National Sleep Foundation Pickwick Award
  Understanding the Link Between Sleep Apnea and Heart Disease

  Obstructive sleep apnea (OSA) is a condition in which breathing is repeatedly interrupted at night as a result of upper airway closure. Not only does OSA lead to sleep deprivation, but it also increases the risk of cardiovascular diseases such as high blood pressure, stroke, and heart attack.
  
  There is growing evidence that OSA is associated with advanced hardening of the arteries (atherosclerosis), which may be responsible in part for its cardiovascular complications. However, the exact reason for these detrimental effects of OSA is unclear. When a person with OSA falls asleep, the upper airway periodically collapses and the body's oxygen levels fall. Safeguards in the central nervous system detect the plummeting oxygen levels and cause the person to awaken and resume normal breathing, restoring oxygen to the body. This repetitive rise and fall of oxygen level is called intermittent hypoxia (IH). Prior studies have shown that cells exposed to IH release free radicals, highly reactive particles that can cause disease. When free radicals attack fat in the bloodstream, substances called oxidized lipids are generated, one of the key ingredients of atherosclerosis.
  
  Dr. Jun's fellowship allowed him to study the pathways by which IH induces atherosclerosis using a mouse model. He first concentrated on the role of an enzyme, NADPH oxidase, in this process. During the course of his research, he found elevations in the level of substances in the blood called free fatty acids (FFA) in intermittent hypoxia, and shifted his focus to FFA. He is now studying FFA elevations during IH in both humans and mice. Dr. Jun's research will expand understanding of the detrimental impact of OSA to human health, which could lead to a reduction in heart-related deaths from OSA. His findings also could be used to develop novel treatments aimed at alleviating the consequences of untreated OSA.

• Vera P. Krymskaya, PHD
  University of Pennsylvania
  American Lung Association/LAM Foundation Career Investigator Award 2005-2008
  Tumor Suppressor Gene May Hold Key to New Treaments in LAM

  Lymphangioleiomyomatosis (LAM) is a rare genetic disorder of unknown origin, which primarily affects women of childbearing age. LAM is characterized by the unusual growth of smooth muscle cells in the interstitium, the supportive tissue between the air sacs of the lungs. These smooth muscle-like LAM cells invade the tissue of the lungs. Their growth destroys lung tissue and obstructs the airways and blood and lymph vessels.
  
  In recent years, a connection has been found between LAM and the loss of function or the mutation of the tumor suppressor gene TSC2. However, there is still much that is not known about how the disruption in the signaling pathway of tumor suppressor genes causes the abnormal growth, proliferation and migration of LAM cells in the lung.
  
  Dr. Krymskaya found that "turning on" the signaling pathway regulated by this gene can stop this LAM cell migration. With her Career Investigator Award, she studied the mechanisms by which TSC2 regulates LAM cell invasive growth. She found that TSC2 plays a critical role in regulating cell migration and invasiveness, which may contribute to the development of LAM. She also found that TSC2 regulates the activity of a protein called Rho GTPase, a discovery that led to a larger grant from the National Heart, Lung, and Blood Institute.
  
  The NHLBI grant has allowed Dr. Krymskaya to conduct a study using a novel combination of two drugs— rapamycin and simvastatin—as a potential treatment for LAM. Dr. Krymskaya previously found that rapamycin inhibits LAM cell growth. The drug is currently being tested in clinical trials as a treatment to slow or stop the growth of LAM cells in the lung. However the drug will not kill LAM cells, and some people will experience side effects from the drug or become resistant to it. Simvastatin, which is well known as a cholesterol lowering drug, and also shows promise as an anti-cancer drug, fights LAM in a different way than rapamycin. It inhibits the activity of Rho GTPase. Unlike rapamycin, which slows or stops the growth of LAM cells, simvastatin appears to kill abnormal LAM cells.
  
  In a recently published study, Dr. Krymskaya has found that mice with LAM-related flank tumors treated with both rapamycin and simvastatin lived longer than those treated with either drug alone. The rapamycin dose used in the combination treatment was much lower than the equivalent human dose being tested as a stand-alone LAM treatment. Many of the mice receiving the combination drug treatment for 50 days survived for a year or more with no recurrence of LAM.
  
  Plans are underway for a clinical trial of the combination rapamycin/simvastatin treatment for LAM.

• Carlos Serezani, PhD
  University of Michigan
  Senior Research Training Fellowship 2008-2010
  Providing New Insights into Lung Immune Defenses

  Immune cells called alveolar macrophages (AM) are on the front line of defense against microbes that cause pneumonia. These cells are responsible for recognizing, ingesting and killing microbes. Dr. Serezani is studying how these cells function, with the hope that the results will lead to better treatments for pneumonia.
  
  Pneumonia-causing bacteria are present in some healthy throats. When body defenses are down, due to causes such as old age, malnutrition, or transplantation, the bacteria can multiply and cause serious damage. Usually, when a person's resistance is lowered, bacteria work their way into the lungs and inflame the air sacs.
  
  With the help of an American Lung Association Senior Research Training Fellowship, Dr. Serezani studied substances called lipid mediators, such as leukotrienes, which can enhance macrophage function during body's fight against pneumonia. Lipid mediators are produced when the body is fighting an inflammatory condition or an infection. They improve clearance of bacteria and boost the immune system's response.
  
  He investigated what happens to the AMs of mice infected with Klebsiella pneumonia when they are treated with leukotrienes. He focused on cell receptors that send signals to direct the activity of AMs. He identified a novel interaction between two types of receptors involved in increasing the microbe-fighting ability of AMs. His findings provide new insights into the immune defenses in the lung.
  
  The American Lung Association Senior Research Training Fellowship allowed Dr. Serezani to apply for and receive a Career Development grant from the National Heart, Lung, and Blood Institute, to further his research.

• Joanne Turner, PhD
  Ohio State University
  Career Investigator Award 2005-2008
  Predicting When Tuberculosis Will Become Infectious

  One-third of the world's population is infected with M. tuberculosis, the germ that causes tuberculosis. However, only a small portion of those individuals will actually develop active infectious disease. This discrepancy is due to the ability of M. tuberculosis to persist within the body for many years in a form often referred to as latency.
  
  In some people this persistent infection is followed by a period of active bacterial growth that produces symptoms of disease and the ability to transmit M. tuberculosis to others. This form of infection is called reactivation. The ability to predict those people who will reactivate their infection would provide a valuable tool that could lead to early detection and treatment of TB, before the onset of symptoms and transmissible infection.
  
  Dr. Turner used an American Lung Association Career Investigator Award to identify immunological markers that change before TB is reactivated. She compared two strains of mice: one susceptible to TB reactivation, and one resistant. Both strains were infected with M. tuberculosis. She found a specific marker in the blood that is indicative of poor disease outcome, and also reflects what is happening in the TB-infected lung. She is continuing this research to identify markers in the blood that not only identify who is likely to reactivate their infection, but can be used to determine when they will reactivate.
  
  One such immune marker is a protein called IL-10.She is studying the role of IL-10 in TB disease progression, to identify the way in which the protein influences the immune response during infection. The ultimate goal is to identify pathways that can be manipulated to prevent reactivation of M. tuberculosis infection, thus reducing transmission.
  
  Dr. Turner's American Lung Association-funded research led to a larger grant from the National Institutes of Health that allowed her to continue and expand her research. Her goal is to use the data she has gathered from mouse studies to transition into research on M. tuberculosis infection in humans. She hopes to be able to develop new diagnostic tests that will indicate a person's risk for reactivation of TB.

• Zhong-Xin Wu, MD
  West Virginia University, Morgantown, WV
  Biomedical Research Grant
  How Does Smoking "in-utero" Lead to Asthma?

  While many studies link embryonic and early environmental tobacco smoke (ETS) exposure with childhood asthma and other lung diseases, the underlying mechanisms that cause these changes in the womb and early life remain unknown. The researchers will study changes in the airways induced by exposure to ETS during early life that potentially leads to increased susceptibility and occurrence of asthma and other lung diseases later in childhood or as adults. They will focus on nerve growth factor (NGF), which is essential in promoting and maintaining growth and survival of the nervous system. Disruption of normal production and release of NGF after inhaling smoke results in changes in the airways which leads to diseaserelated abnormalities in the respiratory system. They will study whether ETS enhances production of NGF during pregnancy and shortly after birth in mice, and examine whether these changes cause increased susceptibility to asthma in early life and beyond, into adulthood.

• Lin Zhang, PhD
  University of Pittsburgh
  American Lung Association/CHEST Foundation Career Investigator Award 2007-2010
  Substance That Controls Cell Death Shows Potential in Treating Lung Cancer

  Apoptosis, or programmed cell death, is a normal suicidal process the body uses to selectively remove cells that are no longer needed, damaged or dangerous. Apoptosis is fundamental to our health; failure of cells to die leads to initiation and progression of cancer, and makes cancer cells resistant to anticancer drugs.

  With his Career Investigator Award, Dr. Zhang was able to identify PUMA, a novel controller of apoptosis and a target of p53, the gene that is altered in the majority of lung tumors. He found that PUMA is important in apoptosis induced by a variety of types of anticancer drugs—not just conventional chemotherapy drugs, but also the more recent targeted therapies, such as erlotinib (Tarceva) and cetuximab (Erbitux), which have been used for treating lung cancer patients. However, he also noted that PUMA is frequently interrupted in lung cancer cells due to abnormalities of p53.

  He then studied the effect of a virus that produces PUMA, called Ad-PUMA, on lung cancer cell growth. When lung cancer cells were infected with Ad-PUMA, their growth was inhibited. A low dose of Ad-PUMA significantly sensitized lung cancer cells to anti-cancer treatments by inducing apoptosis. He also found Ad-PUMA combined with the cancer drug cisplatin was much more effective in killing lung cancer cells compared with cisplatin alone. Finally, Dr. Zhang developed a new screening method that can be used to distinguish anticancer agents that can induce PUMA from those that cannot. Dr. Zhang plans to use this new screening method to identify novel compounds that stimulate PUMA to induce apoptosis in lung cancer cells that are deficient in p53.

• Asthma Clinical Research Centers
  Study of Inactivated Influenza Vaccine in Asthmatics (SIIVA)
  

  Results: The flu vaccine is safe for asthmatics and does not induce an asthma attack.
  [The American Lung Association Asthma Clinical Research Centers.  The safety of inactivated influenza vaccine in adults and children with asthma. New England Journal of Medicine 2001; 345: 1529-36.]
  

• Asthma Clinical Research Centers
  Co-Funded by the Alpha-1 Foundation and Merck
  Effectiveness of Low-Dose Theophylline As Add-On Therapy In Treatment of Asthma (LODO)
  

  Results: Neither montelukast nor low-dose theophylline improved clinical asthma control, although they both improved lung function equally. Inexpensive low-dose theophylline was more beneficial in those patients who had not been prescribed inhaled corticosteroids than montelukast.
  [The American Lung Association Asthma Clinical Research Centers. Clinical trial of low-dose theophylline and montelukast in patients with poorly controlled asthma. American Journal of Respiratory Critical Care Medicine 2007; 175: 235-42]

• Asthma Clinical Research Centers
  Co-Funded by GlaxoSmithKline
  The Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol (LOCCS)
  

  Results: Once-daily fluticasone plus salmeterol was as effective as twice-daily fluticasone treatment, while oral montelukast taken once a day was not as effective. However, montelukast did provide control for most patients.
  [The American Lung Association Asthma Clinical Research Centers. Randomized Comparison of Strategies for Reducing Treatment in Mild Persistent Asthma. New England Journal of Medicine 2007; 356: 2027-39.]

• Asthma Clinical Research Centers
  Co-Funded by the National Institutes of Health’s National Heart, Lung and Blood Institute
  Trial of Asthma Patient Education (TAPE)
  

  Results: Optimistic drug presentation enhances the placebo effect for patient-reported outcomes but not lung function. The effect of montelukast was not enhanced by optimistic messages regarding treatment effectiveness.
  [Wise RA, Bartlett SJ, Brown ED, Castro M, Cohen R, Holbrook JT, Irvin CG, Rand CS, Sockrider MM, and Sugar ES for the American Lung Association Asthma Clinical Research Centers. Randomized trial of the effect of drug presentation on asthma outcomes. Journal of Allergy and Clinical Immunology 2009; 124: 436-44]

• Asthma Clinical Research Centers
  Co-Funded by Schering Plough
  Sinusitis and Rhinitis in Asthma (SIRNA)
  

  Results: A simple, 5-item questionnaire, based on the frequency of nasal symptoms, designed to screen for sinonasal disease was identified and proved more sensitive and specific than sinus CT scans and nasal endoscopy.
  [Dixon A, Sugar E, Zinreich J, Slavin R, Corren J, Naclerio R, Ishii M, Cohen R, Brown E, Wise R, and Irvin C for the American Lung Association Asthma Clinical Research Centers. Criteria to Screen for Chronic Sinonasal Disease. Chest 2009; 136: 1324-1332.]

• Asthma Clinical Research Centers
  Co-Funded by the National Institutes of Health’s National Heart, Lung and Blood Institute
  Study of Acid Reflux in Adults with Asthma (SARA)
  

  Results: The longstanding practice of prescribing heartburn medication is ineffective and unnecessarily expensive for asthma patients who do not exhibit symptoms associated with acid reflux.
  [The American Lung Association Asthma Clinical Research Centers. Efficacy of Esomeprazole for Treatment of Poorly Controlled Asthma. New England Journal of Medicine 2009; 360: 1487-1499.]

• Asthma Clinical Research Centers
  MeCIS: Methacholine Bronchoprovocation: Influence of High Potency Inhaled Corticosteroids
  

  Results: Has been submitted for publication.

• Asthma Clinical Research Centers
  Co-Funded by the National Institutes of Health’s National Heart, Lung and Blood Institute
  SARCA: Study of Acid Reflux and Childhood Asthma
  

  Results: Has been submitted for publication.