Department of Medicine
University of Pittsburgh
A. McGarry Houghton, MD
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Assistant Professor Phone: 412-692-2211 |
Bio
McGarry Houghton received a B.A. in Chemistry from Johns Hopkins University in 1992 and an M.D. from Georgetown University School of Medicine in 1996. After completing an Internal Medicine internship and residency at UT-Southwestern (Parkland Hospital), he joined the Pulmonary and Critical Care Fellowship at Washington University in St. Louis. Dr. Houghton relocated to Boston to continue his research under the mentorship of Steven Shapiro at Brigham and Women's Hospital. He was recruited to join the Division of Pulmonary, Allergy, and Critical Care Medicine faculty at the University of Pittsburgh School of Medicine as an Assistant Professor in September 2006.
Clinical Interests
Dr. Houghton’s clinical research interests involve the impact of tumor-associated inflammation on outcomes in NSCLC. His clinical responsibilities at UPMC include serving as the attending physician on the pulmonary consult service.
Academic and Research Interests
Dr. Houghton’s research interest focus on the role of inflammatory cell-derived proteinases and their target substrates in lung cancer progression. Using mouse models of lung tumorigenesis, he has highlighted the importance of tumor cell products in generating a tumor-associated inflammatory cell profile that promotes tumor growth. Using gene-targeted approaches, Dr Houghton has identified key roles for neutrophil (neutrophil elastase) and macrophage (MMP-12) derived proteinases in tumor progression.
Additionally, Dr. Houghton has developed a new program to study the possible mechanistic links between emphysema and lung cancer by studying tumor progression in the context of cigarette smoke-induce emphysema in mice.
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Hypothesized common origins of emphysema and lung cancer.
Under normal conditions, lung homeostasis is preserved via low-level cell turnover with alveolar macrophages patrolling the lower airspace to remove invading pathogens and particles. Upon exposure to cigarette smoke, inflammatory cells, particularly neutrophils and macrophages, are recruited and activated causing them to release serine and matrix metalloproteinases (MMPs) and reactive oxygen species (ROS). Emphysema results when extracellular matrix destruction and cell death exceeds reparative capacity leading to airspace enlargement. BASCs attempt to replace damaged alveolar cells and maintain alveolar integrity. However, repeated induction of BASC proliferation in the context of cigarette carcinogens and inflammatory proteinase-mediated release of growth factors predisposes these cells to become malignant, leading to bronchogenic carcinoma. Houghton et al., Nature Med 14, 1023-1024 (2008).
Key Publications
Houghton AM, Mouded M, Shapiro SD. Common origins of lung cancer and COPD. Nat Med. 2008 Oct;14(10):1023-4.
Kaynar AM, Houghton AM, Lum EH, Pitt BR, Shapiro SD. Neutrophil elastase is needed for neutrophil emigration into lungs in ventilator-induced lung injury. Am J Respir Cell Mol Biol. 2008 Jul;39(1):53-60. Epub 2008 Feb 14.
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 Jun 15;178(12):8090-6.
Houghton AM, Grisolano JL, Baumann ML, Kobayashi DK, Hautamaki RD, Nehring LC, Cornelius LA, Shapiro SD. Macrophage elastase (matrix metalloproteinase-12) suppresses growth of lung metastases. Cancer Res. 2006 Jun 15;66(12):6149-55.