Margaret Schwarz

Adjunct Professor

A126 Harper Hall
South Bend, IN 46617
+1 574-631-5634

Research Areas

  • Biochemistry

Research Specialties

  • Life Processes
  • Medicine

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Year Title
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 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.

Selected Publications

  • Ranasinghe, A.; Holohan, M.; Borger, K. M.; Donahue, D. L.; Kuc, R. D.; Gerig, M.; Kim, A.; Ploplis, V. A.; Castellino, F. J. and Schwarz, M. A. "Altered Smooth Muscle Cell Histone Acetylome by the SPHK2/S1P Axis Promotes Pulmonary Hypertension" 2023 Circulation Research, 133 (8), pp.704-719. DOI: 10.1161/CIRCRESAHA.123.322740.
  • Awasthi, N.; Schwarz, M. A.; Kaurich, Q.; Zhang, C. H.; Hilberg, F. and Schwarz, R. E. "Enhancing Gastric Cancer Conventional Chemotherapy Effects by Triple Angiokinase Inhibitor Nintedanib in Preclinical Models" 2023 Frontiers in Oncology, 13, 1145999. DOI: 10.3389/fonc.2023.1145999.
  • Ranasinghe, A. and Schwarz, M. A. "Integrating Epigenetics and Metabolomics to Advance Treatments for Pulmonary Arterial Hypertension" 2022 Biochemical Pharmacology, 204, 115245. DOI: 10.1016/j.bcp.2022.115245.
  • Awasthi, N.; Schwarz, M. A.; Zhang, C. H.; Klinz, S. G.; Meyer-Losic, F.; Beaufils, B.; Thiagalingam, A. and Schwarz, R. E. "Augmenting Experimental Gastric Cancer Activity of Irinotecan through Liposomal Formulation and Antiangiogenic Combination Therapy" 2022 Molecular Cancer Therapeutics, 21 (7), pp.1149-1159. DOI: 10.1158/1535-7163.MCT-21-0860.
  • Crawford, K.; Bontrager, E.; Schwarz, M. A.; Chaturvedi, A.; Lee, D. D.; Sazzad, H. M.; von Holzen, U.; Zhang, C. H.; Schwarz, R. E. and Awasthi, N. "Targeted FGFR/VEGFR/PDGFR Inhibition with Dovitinib Enhances the Effects of Nab-Paclitaxel in Preclinical Gastric Cancer Models" 2021 Cancer Biology & Therapy, 22 (10-12), pp.619-629. DOI: 10.1080/15384047.2021.2011642.
  • Hassan, M. S.; Cwidak, N.; Johnson, C.; Daster, S.; Eppenberger-Castori, S.; Awasthi, N.; Li, J.; Schwarz, M. A. and von Holzen, U. "Therapeutic Potential of the Cyclin-Dependent Kinase Inhibitor Flavopiridol on C-Myc Overexpressing Esophageal Cancer" 2021 Frontiers in Pharmacology, 12, 746385. DOI: 10.3389/fphar.2021.746385.