Computational Biology of Molcular & Cell Signaling Pathways of Oncogenic Relevance

Cancer is an umbrella term covering a plethora of conditions characterized by unscheduled and uncontrolled cellular proliferation. What triggers an oncogenic transformation can vary from genetic predisposition, environmental influences, infectious agents, to ageing. These transform normal cells into cancerous ones by derailing a wide spectrum of regulatory and downstream effector pathways. It is just this complexity that has hampered the development of effective and specific cancer therapies. In my lab we have taken a complementary approach to the experimental progress to quantify and interrogate the interactions in molecular and cell signaling pathways implicated in cancers through computational means via a hierarchical multiscale modeling approach based on molecular dynamics and quantum chemical simulations, free energy based molecular recognition algorithms, deterministic network-based kinetic modeling, and hybrid discrete-continuum stochastic dynamics protocols. In my talk I will discuss the foundations and applications of our approach, their utility and predictive value in light of the scope for therapeutic intervention by focusing on two specific cell signaling cascades, namely, DNA repair, and growth factor-mediated proliferation pathways.

Ravi Radhakrishnan, PhD

Ravi Radhakrishnan (Assistant Professor of Bioengineering) obtained his PhD in chemical physics from the Department of Chemical Engineering at Cornell University in 2001. After two postdoctoral assignments in chemical physics and biophysics at MIT and NYU/HHMI, he joined the Penn faculty in 2004. Dr. Radhakrishnan has background in applied mathematics, chemical physics, and molecular biophysics and has extensively developed and applied modeling and simulation protocols to predict single molecule properties as well as signal transduction. Ongoing projects in Dr. Radhakrishnan's lab include finding a molecular basis for DNA repair and replication in oxidatively damaged DNA, searching for new paradigms in drug resistance in cancer therapeutics, and optimizing drug delivery protocols by a rational design of microcarriers. At Penn, Dr. Radhakrishnan has an affiliate appointment in the Department of Biochemistry and Biophysics and membership in Genomics and Computational Biology and the Institute of Targeted Medicine and Therapeutics.