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
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 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 chemotherapeutic 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

  • Awasthi, N., Kronenberger, D., Stefaniak, A., Hassan, M. S., von Holzen, U., Schwarz, M. A., Schwarz, R. E. "Dual inhibition of the PI3K and MAPK pathways enhances nab-paclitaxel/gemcitabine chemotherapy response in preclinical models of pancreatic cancer" 2019 Cancer Letters, 459 pp. 41-49. DOI:10.1016/j.canlet.2019.05.037.
  • Awasthi, N., Mikels-Vigdal, A. J., Stefanutti, E., Schwarz, M. A., Monahan, S., Smith, V., Schwarz, R. E. "Therapeutic efficacy of anti-MMP9 antibody in combination with nab-paclitaxel-based chemotherapy in pre-clinical models of pancreatic cancer" 2019 Journal of Cellular and Molecular Medicine, 23 (6), pp. 3878-3887. DOI:10.1111/jcmm.14242.
  • Lee, D. D., Hochstetler, A., Murphy, C., Lowe, C., Schwarz, M. A. "A distinct transcriptional profile in response to endothelial monocyte activating polypeptide II is partially mediated by JAK-STAT3 in murine macrophages" 2019 American journal of physiology.Cell physiology, 317 (3), pp. C449-C456. DOI:10.1152/ajpcell.00277.2018.
  • Awasthi, N., Schwarz, M. A., Zhang, C., Schwarz, R. E. "Augmentation of nab-paclitaxel chemotherapy response by mechanistically diverse antiangiogenic agents in preclinical gastric cancer models" 2018 Molecular Cancer Therapeutics, 17 (11), pp. 2353-2364. DOI:10.1158/1535-7163.MCT-18-0489.
  • Kuc, N., Doermann, A., Shirey, C., Lee, D. D., Lowe, C., Awasthi, N., Schwarz, R. E., Stahelin, R. V., Schwarz, M. A. "Pancreatic ductal adenocarcinoma cell secreted extracellular vesicles containing ceramide-1-phosphate promote pancreatic cancer stem cell motility" 2018 Biochemical pharmacology, 156 pp. 458-466. DOI:10.1016/j.bcp.2018.09.017.
  • Schwarz, M.A., Lee, D.D., Bartlett, S. "Aminoacyl tRNA synthetase complex interacting multifunctional protein 1 simultaneously binds Glutamyl-Prolyl-tRNA synthetase and scaffold protein aminoacyl tRNA synthetase complex interacting multifunctional protein 3 of the multi-tRNA synthetase complex" 2018 International Journal of Biochemistry and Cell Biology, 99, pp. 197-202. DOI: 10.1016/j.biocel.2018.04.015

Contact Information

  • Adjunct Professor
  • Office: A126 Harper Hall
  • Phone: 574-631-5634
  • Send an email

Primary Research Areas

Research Specialties