Andrei Khokhlatchev, PhD
Signaling in the Ras pathway regulating growth and apoptosis
The Khokhlatchev laboratory is interested in Ras signal transduction and the molecular mechanisms of tumor suppression, focusing on the novel family of tumor suppressors represented by NORE1 and RASSF1. In humans, Ras is the most common dominant oncogene, especially in tumors of epithelial origin. Ras activation often leads to uncontrolled cell proliferation and tumor development. Therefore, it is likely that there are molecular mechanisms in cells that sense the suitability of Ras activation, and in the case of inappropriate activation, blocks cell proliferation or eliminate the cell.
NORE1 was discovered as a protein capable of binding to activated Ras in vitro and in vivo with high affinity. Recent data from several laboratories strongly suggests that NORE1, specifically its longest splice isoform NORE1A, is a tumor suppressor. The current hypothesis is that NORE1 is the key regulator in Ras signaling, determining an outcome of proliferation or cell cycle arrest or apoptosis. To understand the molecular mechanisms of NORE1 tumor suppression, the laboratory is performing structure-functional studies of NORE1A to determine and characterize regions of the molecule essential for growth and tumor suppression and is studying mechanism of NORE1A activation by Ras. Subsequently, components of growth-inhibitory signal transduction pathway that starts at NORE1A will be identified and molecular mechanism of their action will be characterized. In addition, recent studies by the lab determined that NORE1A is capable to bind microtubules. The significance of this interaction for NORE1A-induced growth and tumor suppression will be determined.