Martin Steffen, MD, PhD

Study on Protein and Lung Disease Reveals Surprises

Dr. Steffen’s Biomedical Research Grant from the American Lung Association originally focused on the role of a protein called proteasome in chronic obstructive pulmonary disease (COPD). Proteasome is a key protein complex known to regulate several processes that cause inflammation, and which has previously been implicated in the development of diabetes and heart disease.

Wu CJ, Cai T, Rikova K, Merberg D, Kasif S, Steffen M. “A predictive phosphorylation signature of lung cancer” PLoS One. 4(11):e7994 (2009 Nov 25).
He isolated proteasome complexes from people with and without COPD, in order to identify differences between the two groups. He compared the protein and chemical composition of the complexes, and tested their functional activity. He was unable to consistently identify differences in protein composition between the two groups.

Fortunately, during his research, he was able to start a very successful line of inquiry on lung cancer. Dr. Steffen’s research centered on a process called phosphorylation, which can turn a protein “on” or “off.”

He identified a number of proteins whose activation allows them to distinguish between cancer cells and normal cells with almost 97 percent accuracy. He also developed a new way to identify key biological pathways that are active in cancer, but not in normal cells. He says his findings will ultimately lead to the development of drugs aimed at inhibiting these cancer-related pathways.

“Despite the fact that these studies represent a very significant departure from the originally proposed experiments, they are squarely aimed at reducing the burden of lung disease in patients, and illuminate biological mechanisms associated with the disease,” Dr. Steffen says.

He is now focused on developing a test to predict lung tumor sensitivity for the drug erlotinib. He hopes to expand this research to include other cancer drugs.

Based on his American Lung Association-funded research, Dr. Steffen applied for further grants to continue his investigations.