Department of Medicine

University of Pittsburgh

Division of Pulmonary, Allergy, and Critical Care Medicine
3459 Fifth Avenue,
628 NW
Pittsburgh, PA 15213
Academic Office: (412) 692-2210
Comprehensive Lung Center (Patient Care and Referral): (412) 648-6161

Steven D. Shapiro, MD

Executive Vice President, UPMC
Chief Medical and Scientific Officer
President, Physician Services Division
Professor of Medicine

Assistant: Paula Nave
Assistant Email:


Dr. Shapiro is the Executive Vice President and Chief Medical and Scientific Officer, UPMC and the President of the Physician Services Division.  Dr Shapiro obtained BS and MD degrees from the University of Chicago.  He completed his internship, medicine residency, chief residency, and pulmonary & critical fellowship all at Barnes-Jewish Hospital of Washington University School of Medicine in St. Louis.  He later joined the faculty at Washington University and was appointed Professor of Medicine, Pediatrics, and Cell Biology in 2000.  Dr Shapiro relocated to Boston in 2001 to become the Parker B. Francis Professor and Chief of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital, Harvard Medical School, before leaving for Pittsburgh in 2006.

Academic and Research Interests

Dr. Shapiro’s laboratory focuses on the role of inflammatory cell derived proteinases in the progression of COPD/emphysema and lung cancer.  He originally cloned and knocked-out macrophage elastase (MMP-12) to demonstrate that MMP-12 deficient mice are completely protected from the development of cigarette smoke-induced emphysema.  Dr. Shapiro’s lab has continued to study the contribution of numerous inflammatory cell derived proteinases in emphysema and lung cancer progression using gene targeting in mice.  More recently, his lab has begun to study the role of repair (or lack thereof) in the progression of emphysema by using lineage-tagging approaches to study putative stem cell populations residing within the lung.

Shapiro, New Engl. J. Med. 5/05

Inflammatory-Cell Interactions in Chronic Obstructive Pulmonary Disease (COPD) and the Role of Histone Acetylation.
Reactive oxygen species resulting from inhaled cigarette smoke (and potentially from the inflammatory cells themselves) promote transcription of nuclear factor-κB (NF-κB)–mediated proinflammatory factors by way of two mechanisms. First, oxidation results in the degradation of IK-κB, releasing NF-κB, which then translocates to the nucleus of the targeted cell. Oxidation also inactivates histone deacetylase (HDAC), shifting the balance to increased DNA acetylation, weakening the interactions between histone and DNA and "unwinding" DNA, allowing NF-κB greater access to the DNA promoter elements, and leading to transcription of neutrophil chemokines and cytokines (tumor necrosis factor TNF-1α and interleukin-8) and matrix metalloproteinases (MMPs). These factors recruit and activate neutrophils to the lung. In addition, CD8+ T cells augment the production of macrophage MMPs through interactions with surface-bound CD40 molecules and interferon-inducible chemokines (inducible protein of 10 kD [IP-10], interferon-inducible T-cell alpha chemoattractant [I-TAC], and monokine induced by interferon-γ[MIG]). Macrophage MMPs and neutrophil elastase degrade each other's inhibitors, the tissue inhibitor of metalloproteinases and alpha1-antitrypsin, respectively, augmenting their matrix-degrading capacities. These interactions illustrate the highly interactive nature of the immune inflammatory response and suggest that breaking this cycle, perhaps by way of augmentation of HDAC with the use of theophylline, may prevent inflammatory-mediated destruction of the lung in COPD. Dashed lines indicate inhibition.


Figure 2

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, Quintero PA, Perkins DL, Kobayashi DK, Kelley DG, Marconcini LA, Mecham RP, Senior RM, Shapiro SD.  Elastin fragments drive disease progression in a murine model of emphysema.  J Clin Invest. 116, 753-759 (2006).

Belaaouaj A, McCarthy R, Baumann M, Gao Z, Ley TJ, Abraham SN, Shapiro SD.  Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis.  Nat Med. 4, 615-618 (1998).

Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD.  Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice.  Science 277, 2004-2004 (1997).

PubMed Link


Dr. Shapiro was featured in PittMed magazine in 2007