Mount Sinai - Iyengar Laboratory - Department of Pharmacology and Systems Therapeutics

Padmini Rangamani, M.S.

Ph.D. Student, Department of Pharmacology and Systems Therapeutics
E-mail: padmini.rangamani@mssm.edu

Mailing Address

One Gustave L. Levy Place, Box 1215 New York NY 10029

Training and Education

M.S. (2005) Georgia Institute of Technology, Atlanta, GA, USA

B.Tech. (2001) Osmania University, Hyderabad, India

Research Interests

Cell spreading on a substrate is a highly integrated multi-step process with complex signaling pathways that are spatially and temporally regulated. Cell spreading and motility are important for many physiological processes such as embryonic development and wound healing. Initiation of cell spreading occurs due to actin cytoskeleton remodeling in response to signaling via the integrin receptors. Actin cytoskeleton remodeling is achieved by the following biochemical reactions mediated by actin modulators: filament elongation (profilin), branching (Arp2/3), capping (gelsolin) and depolymerization (cofilin). The signaling mechanism from the integrin receptors to the actin remodeling proteins is complex and involves kinases, lipids, Rho family of small-GTPases, scaffolding proteins and the actin modulators themselves. The balance between the biochemical reactions governing actin filaments is delicate and is fine-tuned by the upstream signaling. Spatial regulation is very important for integrin mediated signaling since spatial changes in the cytoskeleton determine the cell spreading process. Because of the nature of the interactions between plasma membrane components and cytoplasmic components, the local membrane curvature of the plasma membrane determines the localization of signaling domains. Thus, cell spreading is governed by an intricate balance in the spatio-temporal dynamics of signaling between the plasma membrane and cytoplasm. Mathematical modeling of this signaling process allows us to use an integrated approach and gain insights into the mechanistic aspects of cytoskeletal remodeling. Additionally, modeling generates new hypotheses that may be tested experimentally.

The overall goal of this project is to develop mathematical models for the integrin mediated signaling leading to cytoskeletal remodeling. The model will be developed with the aim of determining the role of upstream signaling components in balancing actin remodeling.

Publications

Rangamani P, Iyengar R. Modelling cellular signalling systems. Essays Biochem. 2008;45:83-94.

Neves SR, Tsokas P, Sarkar A, Grace EA, Rangamani P, Taubenfeld SM, Alberini CM, Schaff JC, Blitzer RD, Moraru II, Iyengar R. Cell shape and negative links in regulatory motifs together control spatial information flow in signaling networks. Cell. 2008 May 16;133(4):666-80.

Rangamani P, Sirovich L. Survival and apoptotic pathways initiated by TNF-alpha: Modeling and predictions. Biotechnol Bioeng. 2007 Aug 1;97(5):1216-29.

Rangamani P, Iyengar R. Modelling spatio-temporal interactions within the cell. J Biosci. 2007 Jan;32(1):157-67.

Patent Pending

Chemical treatment for removing cellular and nuclear material from naturally occurring extracellular matrix based biomaterials, filed with the U.S. Patent and Trademark Office in October 2004.