- Research Associate Professor, University of Notre Dame
- Research Assistant Professor, University of Notre Dame
- Walther Cancer Research Fellow, University of Notre Dame
- Postdoctoral Fellow, University of Notre Dame
- NIH Training Fellow, University of Illinois Urbana-Champaign
- Postdoctoral Fellow, University of Illinois Urbana-Champaign
- Ph.D. in Molecular Biology, Bombay University
- M.S. in Molecular Biology, Bombay University
- B.S. in Microbiology, Bombay University
- Young Scientist Fellowship
- Council of Scientific and Industrial Research Fellowship, Government of India
Angiogenesis is an important process of forming new vessels that occurs in both physiological and pathophysiological settings. This process is a multistep event involving several proteins that function in a spatially and temporally controlled microenvironment. Components of the fibrinolytic pathway, namely plasminogen (Pg), urokinase plasminogen activator (uPA), its receptor (uPAR), tissue-type plasminogen activator (tPA), and the physiological inhibitor plasminogen activator inhibitor-1 (PAI-1) are some of the key players involved in angiogenic events. The process of angiogenesis is initiated by activation of the normally quiescent endothelial cells, degradation of the extracellular matrix, followed by cellular proliferation, migration, adhesion, and finally formation of capillary sprouts. Discerning the involvement of the individual fibrinolytic proteins in angiogenesis has been facilitated by utilizing primary endothelial cells obtained from various knockout mice (PAI-1-/-, uPA-/-, uPAR-/-, tPA-/-).
The fibrinolytic proteins are also known to transduce cell signaling by activation of tyrosine kinase receptors, such as, VEGR1 and VEGFR-2 to promote cell survival. Our studies have implicated a novel role of PAI-1 in modulating the Akt, and the JAK/STAT pathway thereby affecting endothelial apoptosis and cell cycle progression. Current studies involve elucidating the role of uPAR in endothelial cell adhesion and its ability to affect cell morphology. Organization of F-actin fibers, and cellular localization of phosphorylated Focal Adhesion Kinase (FAK) and vincullin are dramatically different in uPAR-/- endothelial cells compared to the WT cells. Furthermore, the ability of the receptor to modulate changes in cell morphology and adhesion is dependent on uPAR-mediated cell binding to the matrix via regulation of integrin signaling.
Therefore, the primary focus of interest is to study the role of fibrinolytic pathway components in events associated with angiogenesis, as well as to provide mechanisms by evaluating the underlying signal transduction pathways. The angiogenic study involves cell-based assays, molecular biology, and recombinant protein work, as well as utilizing cutting edge technology, such as, confocal microscopy and real-time microscopy.
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- Qiu, C., Yuan, Y., Zajicek, J., Liang, Z., Balsara, R.D., Brito-Robionson, T., Lee, S.W., Ploplis, V.A., Castellino, F.J. "Contributions of different modules of the plasminogen-binding Streptococcus pyogenes M-protein that mediate its functional dimerization" 2018 Journal of Structural Biology, Article in Press. DOI: 10.1016/j.jsb.2018.07.017
- Yuan, Y., Balsara, R.D., Zajicek, J., Kunda, S., Castellino, F.J. "Discerning the Role of the Hydroxyproline Residue in the Structure of Conantokin Rl-B and Its Role in GluN2B Subunit-Selective Antagonistic Activity toward N-Methyl-d-Aspartate Receptors" 2016 Biochemistry, 55 (51), pp. 7112-7122. DOI: 10.1021/acs.biochem.6b00962
- Johnson, J.J., Miller, D.L., Jiang, R., Liu, Y., Shi, Z., Tarwater, L., Williams, R., Balsara, R., Sauter, E.R., Stack, M.S. "Protease-activated Receptor-2 (PAR-2)-mediated Nf-κB activation suppresses inflammation-associated tumor suppressor MicroRNAs in oral squamous cell carcinoma" 2016 Journal of Biological Chemistry, 291 (13), pp. 6936-6945. DOI: 10.1074/jbc.M115.692640
- Cheriyan, J., Balsara, R.D., Hansen, K.B., Castellino, F.J. "Pharmacology of triheteromeric N-Methyl-d-Aspartate Receptors" 2016 Neuroscience Letters, 617, pp. 240-246. DOI: 10.1016/j.neulet.2016.02.032