Margaret Schwarz

Margaret Schwarz

Mechanisms of Cancer Progression

Biography

2014-present
Adjunct Professor, Department of Chemistry and Biochemistry, University of Notre Dame
2013-present
Professor, Department of Pediatrics and Integrative Biology Graduate Program, Indiana University School of Medicine, South Bend, IN
2007-2013
Associate Professor, Department of Pediatrics, Division of Critical Care, Division of Pulmonary and Vascular Biology, Integrative Biology Graduate Program, UT Southwest Medical Center, Dallas, TX
2004-2007
Associate Professor, Department of Surgery, Division of Surgical Sciences; Department of Pediatrics, UMDNJ Robert Wood Johnson Medical School
2001-2004
Assistant Professor, Department of Surgery, Division of Surgical Sciences; Department of Pediatrics, UMDNJ Robert Wood Johnson Medical School
2000-2001
Director, Pediatric Critical Care Fellowship, Children's Hospital of Los Angeles
1996-2001
Assistant Professor, Department of Pediatrics, Critical Care Medicine, Division of Cardiothoracic Critical Care, University of Southern California
1994-1996
Assistant Professor, Department of Pediatrics, Division of Critical Care Medicine, Columbia University, New York
1993-1994
Instructor, Department of Anesthesia, Division of Pediatrics Critical Care Medicine, University of Pittsburgh
1990-1993
Fellowship, Pediatric Critical Care, Children's Hospital of Pittsburgh, Pittsburgh, PA
1988-1990
Pediatric Residency, Children's Hospital, Columbus, OH
1987-1988
Pediatric Internship, Children's Hospital, Columbus, OH
1987
M.D., University of Missouri Six-Year Medical School
1986
B.A.in Biology, University of Missouri

Selected Awards

2009
Member, Society of Pediatric Research
1998
Dr. Edward Livingston Trudeau Scholar, American Lung Association
1995
Finalist for the Louis N. Katz Basic Science Research Prize, American Heart Association
1994
Pediatric Research Award, Society of Critical Care Medicine
1993-1998
Clinician Scientist Award, American Heart Association

Research Interests

The Schwarz lab uses transgenic mice, three dimensional cell culture, in vivo tumor, and lung developmental models to determine mechanisms by which the vasculature regulates cancer progression and alveolar formation.

Our main interests are the role that the anti-angiogenic mediator Endothelial Monocyte Activating Polypeptide II (EMAP II, also known as AIMP-1, Scye-1, and p43) has in lung and tumor development. On the cell surface, EMAP II undergoes proteolytic cleavage to generate an extracellular »22-kDa C-terminal peptide that functions as an anti-angiogenic protein through inhibition of endothelial cell adhesion to fibronectin, blockade of fibronectin matrix assembly via a5b1 integrin, and interference with vascular endothelial growth factor (VEGF) induced pro-angiogenic signaling.

Earlier studies identified a direct interaction between vascular growth factors and the regulation of tissue formation. Using pulmonary developmental models, we have shown that vascular growth factors can also impact epithelial –mesenchymal transdifferentiation, extracellular matrix deposition, and airway simplification resulting in physiologic changes in pulmonary function. Currently, our studies focus on the mechanisms that modulate pulmonary vascular growth and the subsequent impact that the vasculature has on alveolar growth by examining vessel mediation of interstitial lung disease, deposition of the extracellular matrix protein, and epithelial cell proliferation.

By using a pancreatic cancer models (intraperitoneal and subQ), targeted multi-drug therapy strategies are utilized to determine the role that anti-angiogenic factors alone and in combination with chemotherpeutic agents have in regulating tumor cell proliferation and microenvironment including the dense tumor stromal layer, extracellular matrix deposition and vessel formation. Recent studies utilizing this strategy demonstrated that this multi-target approach is effective and superior to current conventional chemotherapeutic strategies.

Recent Papers

  • Lee, D.D.; Lal, C.V.; Persad, E.A.; Lowe, W.; Schwarz, A.M.; Awasthi, N.; Schwarz, R.E.; Schwarz, M.A. "EMAP II Mediates Macrophage Migration in Development of Hyperoxia-Induced Lung Disease of Prematurity." Am. J. Respir. Cell Mol. Biol. 2016, PMID:27254784.
  • Lee, D.D.; Schwarz, M.A. "Adapted approach to profile genes while reconciling Vegf-a mRNA expression in the developing and injured lung." Am. J. Physiol. - Lung C. 2015, 308 (12), L1202-1211.
  • Xu, H.M.; Malinin, N.L.; Awasthi, N.; Schwarz, R.E.; Schwarz, M.A. "The N Terminus of Pro-endothelial Monocyte-activating Polypeptide II (EMAP II) Regulates Its Binding with the C Terminus, Arginyl-tRNA Synthetase, and Neurofilament Light Protein." J. Biol. Chem. 2015, 290 (15), 9753-9766.
  • Awasthi, N.; Hinz, S.; Brekken, R.A.; Schwarz, M.A.; Schwarz, R.E. "Nintedanib, a triple angiokinase inhibitor, enhances cytotoxic therapy response in pancreatic cancer." Cancer Lett. 2015, 358 (1), 59-66.
  • Yuan, C.; Yan, L.; Solanki, P.; Vatner, S.F.; Vatner, D.E.; Schwarz, M.A. "Blockade of EMAP II protects cardiac function after chronic myocardial infarction by inducing angiogenesis." J. Mol. Cell. Cardiol. 2015, 79, 224-231.
  • Awasthi, N.; Zhang, C.H.; Schwarz, A.M.; Hinz, S.; Schwarz, M.A.; Schwarz, R.E. "Enhancement of Nab-Paclitaxel Antitumor Activity through Addition of Multitargeting Antiangiogenic Agents in Experimental Pancreatic Cancer." Mol. Cancer Ther.  2014, 13(5), 1032-1043.

Contact Information

Primary Research Areas

Research Specialties