Steven D. Shapiro, MD
Jack D. Myers Professor and Chair
Email: shapiros@dom.pitt.edu
Research Interest:
Dr. Shapiro is The Jack D. Myers Professor and Chair of the Department of Medicine at University of Pittsburgh. He was formerly the Parker B. Francis Professor of Medicine at Harvard Medical School and Chief of Pulmonary and Critical Care Medicine at Brigham and Women's Hospital. His scientific career has focused on understanding the biological functions of matrix degrading proteinases in general and COPD in particular.
His laboratory developed a model of cigarette smoke-induced emphysema in mice and generated mice deficient in candidate proteinases by gene targeting to directly determine the contribution of individual proteinases to COPD. Applying these mutant mice to this model, he determined that MMP-12 and to a lesser degree neutrophil elastase are required for the development of emphysema as well as macrophage recruitment in COPD. This finding has changed the paradigm regarding COPD pathogenesis.
His laboratory has also generated "knockout" mice to determine other biological and pathological functions of proteinases. For example, they found that neutrophil elastase plays an important role in fighting Gram negative bacterial infections by degrading outer wall Omp proteins. MMP-12 also appears to have unique host defense properties, being the only directly antimicrobial MMP and the one MMP that limits, rather than promotes, tumor progression.
Current directions include continuing to determine the biological and pathological function of proteinases. With respect to COPD the goals are to understand the process of repair and to utilize stem cells and bioengineered extracellular matrix to improve lung function. Use of a multidisciplinary approach to COPD is a major focus that we hope will lead to disease modifying therapy.
Dr. Shapiro has maintained his clinical interests while pursuing his research and still is involved in clinical care and teaching.
Recent Publication
Maeno T, Houghton AM, Quintero PA, Grumelli S, Owen CA, Shapiro SD. CD8+ T cells are required for inflammation and destruction in cigarette smoke-induced emphysema in mice. J. Immunol. 2007; 178:8090-96.
Xu J, Tian J, Grumelli SM, Haley KJ, Shapiro SD. Stage-specific effects of cAMP signaling during distal lung epithelial development. J Biol Chem. 2006; 281:38894-38904.
Maeno T, Houghton AM, Quintero PA, Grumelli S, Owen CA, Shapiro SD. CD8+ T cells are required for inflammation and destruction in cigarette smoke-induced emphysema in mice. J. Immunol. 2007; 178:8090-96.
Houghton AM, Quintero PA, Perkins DL, Kobayashi DK, Kelley DG, Marconcini LA, Mecham RP, Senior RM, Shapiro SD. Elastin fragments drive disease progression in a mouse model of emphysema. J. Clin. Invest. 2006; 116:753-759.
Houghton AM, Grisolano JL, Baumann ML, Kobayashi DK, Corneliu LA, and Shapiro SD. Macrophage elastase (MMP-12) suppresses growth of lung metastases. Cancer Res. 2006; 66:6149-55.
Shapiro SD. COPD unwound. New Engl J Med. 2005; 12;352:2016-2019Riese RR, Finn PW, and Shapiro SD. Influenza and asthma: adding to the respiratory burden. Nature Immunology 2004; 5:243-244
Kreindler JL, Shaprio SD. Lung turns to AA (adenosine analogues) to dry out. Nat Med. 2007; 13: 406-8.
