Rashna Balsara, PhD

Research Assistant Professor, Department of Chemistry and Biochemistry, University of Notre Dame

Education
BS, University of Bombay (India), 1985
PhD, University of Bombay, (India), 1998
Post-doctoral fellow, University of Ilinois     (Urbana/Champaign), 1998-2002

Post-doctoral fellow, University of Notre Dame, 2002-2005

Walther Cancer Research Center Fellow, University of Notre Dame, 2005-2007

Address
W. M. Keck Center for Transgene Research
230 Raclin-Carmichael Hall
University of Notre Dame
Notre Dame, IN 46556

Contact
Phone: (574) 631-2958
Fax: (574) 631-4048

E-mail:  rbalsara@nd.edu

Honor and Awards

1986-1989 Lady Tata Memorial Trust Fellowship

1991-1996 Council of Scientific and Industrial Research

Memberships and Committees

Life Member of Environment Mutagen Society of India

Other Activities

2007 Editorial Board of Current Drug Targets

Research Interests

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.

Selected Recent Publications

Huang L, Balsara RD, Sheng Z, Castellino FJ.  (2010)  Conantokins inhibit NMDAR-dependent calcium influx in developing rat hippocampal neurons in primary culture with resulting effects on CREB phosphorylation. Mol Cell Neurosci.  45:163-172.

Balsara RD, Xu Z and Ploplis VA (2007).  Targeting Plasminogen Activator Inhibitor-1: Role in cell signaling and the biology of domain-specific knock-in mice.  Current Drug Targets 8:982-995.

Balsara RD, Castellino FJ, and Ploplis VA (2006).  A novel function of plasminogen activator inhibitor-1 in modulation of the Akt pathway in wild-type and plasminogen activator inhibitor-1-deficient endothelial cells. J Biol Chem. 281:22527-22536.

Xu Z, Balsara RD, Gorlatova NV, Lawrence D, Castellino FJ and Ploplis VA (2004). Conservation of critical functional domains in murine plasminogen activator inhibitor-1. J Biol Chem. 279: 17914-17920.

Ploplis VA, Balsara RD, Sandoval-Cooper M, Yin ZJ, Batten J, Modi N, Gadoua D, Donahue D, Martin JA and Castellino FJ (2004. ) Enhanced in vitro proliferation of aortic endothelial cells from plasminogen activator inhibitor-1-deficient mice. J Biol Chem 279: 6143-6151.

Rajendran R, Nye A, Frasor J, Balsara RD, Martini P, Belmont A and Katzenellenbogen BS (2003). Regulation of nuclear receptor transcriptional activity by novel DEAD box RNA helicase (DP97). J Biol Chem. 278: 4628-4638.

Xie L, Chatterjee C, Balsara RD, Okeley NM and van der Donk W (2002).  Heterologous expression and purification of SpaB involved in subtilin biosynthesis. Biochem Biophys Res Comm. 295: 952-957.