Midland States Research

American Lung Association Research Projects in the Midland States
                                              2012-2013

Researcher

Topic Area

Emilie Bourdonnay, PhD

Lung Infections

James Bridges, PhD

Asthma & COPD

Gang Chen, PhD

Asthma & COPD

Ramesh Ganju, PhD

Lung Cancer

Alison Mcleish, PhD

Asthma & COPD

Minal Patel, MPH

Asthma & COPD

Venuprasad Poojary, PhD

Lung Cancer

Lobelia Samavati

Interstitial Lung Disease

Zbigniew Zaslona, PhD

Asthma & COPD

Igor Zelko, PhD

Acute Lung Injury

KENTUCKY

 Igor Zelko, PhD
University of Louisville, Louisville, KY
Biomedical Research Grant

Blocking Remodeling in Lung’s Blood Vessels in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a devastating disease; only about half of patients survive five years after diagnosis. The lung’s blood vessels are remodeled and constrict, leading to heart failure due to an enlarged and ineffective right side of the heart. Current drugs used to treat the disease enlarge the blood vessels, but do not block the eventual thickening of the artery walls and do not improve survival. More effective therapies are urgently needed.

With the assistance of an American Lung Association Biomedical Research Grant, Igor Zelko, PhD, is studying the mechanisms that regulate remodeling of blood vessel walls in the lung. He is focusing on a substance that inhibits an enzyme called histone deacetylase, which he hopes will provide clues that could lead to better therapy for PAH.

A process called acetylation, or modification of histones regulates the expression of a major antioxidant enzyme in the pulmonary arteries. Dr. Zelko is investigating whether histone deacetylase inhibitors will significantly elevate levels of this antioxidant enzyme, called extracellular superoxide dismutase, which in turn will reduce or completely block remodeling of the lung’s blood vessel walls and slow or prevent the development of PAH in a mouse model.

“If it is successful, eventually this drug could be used in human trials to stop, or even reverse progression of the disease,” Dr. Zelko says.

He is particularly grateful to the American Lung Association for funding his research. “My startup funding had ended, and if I had not received the American Lung Association grant, I could not have continued this research, which I have been working on for the last 10 years,” he said.

MICHIGAN

 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.

 Minal R. Patel, MPH
University of Michigan, Ann Arbor, MI
Lung Health Dissertation Grant

Talking to the Doctor About the Cost of Managing Asthma

Some people may experience problems with the cost of managing their asthma due to reasons that may not necessarily have to do with having health insurance or the means to pay for health care. Ms. Patel will see if women who talk to their doctor about asthma-related financial concerns have better asthma outcomes and will investigate what kinds of patients experience cost-related problems with their asthma management and want to talk about this with their doctor. Ms. Patel will also study what factors related to asthma cause patients to experience cost-related problems, and if talking to a doctor about cost is related to how people manage their asthma and their use of health services. The results of the study may help design programs for doctors and other health care providers that teach them how to talk about cost with their patients, especially African American women who experience the most problems with asthma management.

 Venuprasad Poojary, PhD
Wayne State University, Detroit, MI
Biomedical Research Grant

Understanding How Lung Inflammation Leads to Cancer  

Lung cancer is the major cause of cancer-related deaths for both men and women in the United States. Lung inflammation associated with chronic obstructive pulmonary disease (COPD), cigarette smoking, exposure to asbestos and silica is closely linked to the development of lung cancer. However, the molecular mechanisms that link lung inflammation and cancer progression remain unclear. Dr. Poojary hopes to better understand a novel regulatory mechanism in the inflammatory cells which plays a critical role in the termination of tumor-promoting inflammation. The information obtained from these studies could lead to therapeutic interventions to target inflammatory cells in the tumor

 Lobelia Samavati
Wayne State University, Detroit, MI
Biomedical Research Grant

How Immune System Works Differently in Sarcoidosis  

Sarcoidosis is an inflammatory disorder that can affect multiple organs throughout the body. Its is unknown what causes the disease and its course and outcome are difficult to predict in each individual patient. Immune protein cells in the body are equipped to recognize these invaders, triggering an inflammatory response in an attempt to kill the invading foreign pathogens. In healthy individuals, inflammation shuts down once an infection is fought off; however, this process remains sustained in sarcoidosis patients. Dr. Samavati will investigate why these immune proteins work differently and how the inflammatory process continues to be activated in sarcoidosis patients compared to healthy individuals. The findings may lead to more effective drug therapies.

 Zbigniew Zaslona, PhD
University of Michigan, Ann Arbor, MI
Senior Research Training Fellowship

Deciphering Macrophages’ Role in Asthma  

Alveolar macrophages (AMs) are immune cells that play a pivotal role in the coordination of inflammatory responses in the lung. AM numbers are elevated in asthma, but the mechanisms responsible for this are poorly understood. Dr. Zaslona will study substances called eicosanoids which participate in many biologic processes, including inflammation. He will study the role of certain eicosanoids in controlling accumulation of AMs and their activation in asthma. Using a mouse model, Dr. Zaslona will investigate whether one eicosanoid, prostaglandin E2, decreases AM accumulation in asthma, while another one, leukotriene, increases it. The findings will provide new insight into macrophage regulation in allergic asthma. Since drugs that modify the actions of eicosanoids are already available or in development, their results may directly translate to improved therapies for asthma.

OHIO

 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.

 Gang Chen, PhD
Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
Senior Research Training Fellowship

Gene May Provide Clue to Mucus Production  

The reason the lungs of patients with chronic lung disease such as asthma, cystic fibrosis and chronic obstructive pulmonary disease clog with thick mucus, leading to infection and inflammation, is unclear. There are only a few treatments available to treat this mucus, and they are often not very effective. Dr. Chen will identify the biological function of a gene called FOXA3, which is “quiet” in healthy lungs but heavily increased in lung cells that produce mucus in patients with chronic lung diseases. Preliminary studies demonstrated that FOXA3 has a dual role in the lung’s epithelia, cells that line the airways - controlling mucus production and suppresses lung inflammation. Dr. Chen will identify the momolecular mechanisms of FOXA3 that influence lung epithelial cell function in health and disease. This will help identify new pharmacological targets to treat chronic lung diseases, and will provide new strategies for diagnosis, prevention and treatment of these diseases.

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

Can an Enzyme Really Cause So Much Damage?  

About 90 percent of lung cancers are non-small cell lung cancer (NSCLC). Many patients with the disease become resistant to chemotherapy, and fewer than 20 percent live beyond five years after diagnosis. Dr. Ganju will investigate whether an enzyme called fatty acid amid hydrolase (FAAH) can interfere with a natural brain compound that he believes can block the growth and spread of lung cancer. These natural brain compounds, known as endocannabinoids, attaches to receptors called CB1 and CB2. These are found on cells that regulate the progression and spread of NSCLC to other organs and systems. He will test the ability of endocannabinoids to block the growth and spread of cancer and whether this process is stopped by FAAH in mice. The results of this award may lead to future research that could lead to new treatments for NSCLC to help people live longer.

 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. Dr. McLeish 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 project results will hopefully lead to the development of specialized smoking cessation programs for people with asthma.