Margaret Schwarz

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

• 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.
• Grojean, M.; Schwarz, M. A.; Schwarz, J. R.; Hassan, S.; Holzen, U. V.; Zhang, C. H.; Schwarz, R. E. and Awasthi, N. "Targeted Dual Inhibition of C-Met/VEGFR2 Signalling by Foretinib Improves Antitumour Effects of Nanoparticle Paclitaxel in Gastric Cancer Models" 2021 Journal of Cellular and Molecular Medicine, 25 (11), pp.4950-4961. DOI: 10.1111/jcmm.16362.