A computationally-designed inhibitor molecule (gray) interacts snuggly with its target domain (yellow) to prevent cancer-promoting activities.

A computationally-designed inhibitor molecule (gray) interacts snuggly with its target domain (yellow) to prevent cancer-promoting activities.

Research Project 3

Protein Design for Selective Interference with LPA Signaling in Colon Cancer

Gevorg Grigoryan, PhD

Colorectal cancer was the third-most common cause of deaths from cancer in the United States in 2013. This disease claims over 50,000 lives and afflicts over 140,000 people annually in the US, underscoring a clear and urgent need for better control of this incurable malignancy. The goal of our study is to attenuate oncogenic activities in colon cancer cells by inhibiting a key proliferatory signaling pathway mediated by the powerful mitogen lysophosphatidic acid (LPA). Key towards this goal is to produce selective inhibitors—molecules that interact with and inhibit specific proteins in the cell, while avoiding any unintended side-interactions with other proteins. We are uniquely capable of providing such selectivity using computational technologies we have developed that enable us to target selectively a single member in a family of closely related protein domains.