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Andrei  Khokhlatchev
Degree(s): Ph.D.
Graduate School: University of Texas Southwestern Medical Center at Dallas
Primary Appointment: Assistant Professor of Pathology
Research Interests:
Molecular Mechanisms of Tumor Suppression by NORE1A family of Proteins

Email Address: ak9k@virginia.edu
Biomedical Sciences Graduate Program(s)
  • Molecular Medicine
    • Research Description

    Our laboratory is interested in Ras signal transduction and the molecular mechanisms of tumor suppression, specifically within the novel family of tumor suppressors represented by NORE1 and RASSF1. In humans, Ras is the most common dominant oncogene, frequently activated by mutation. 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. Data obtained by us and others suggests that NORE1, specifically its longest splice isoform NORE1A, is a tumor suppressor, affected in lung, breast, colorectal, kidney and other cancers. Our hypothesis is that NORE1 is the key regulator in Ras signaling, determining an outcome of proliferation or cell cycle arrest or apoptosis. Currently, we are focused on structure-functional studies of NORE1A to determine and characterize regions of the molecule essential for growth and tumor suppression, studying mechanism of NORE1A activation by Ras and identifying components of growth-inhibitory signal transduction pathway that starts at NORE1A.


    RASSF1 is located on human chromosome 3p21, among a cluster of putative tumor suppressor genes. This cluster is frequently deleted in lung tumors, as well as in many breast, renal, hepatic, prostate, head/neck and other cancers. Forced expression of the RASSF1A gene in such tumor cell lines substantially suppresses their growth rate in vitro and in vivo. RASSF1 is closely related to NORE1; however, RASSF1 cannot bind Ras. To understand the mechanism of RASSF1A tumor suppression, we are going to investigate how this protein is activated, specifically at what conditions it is capable to bind Ras.


    Selected Publications
  • Praskova M., Khoklatchev A., Ortiz-Vega S., Avruch J. Regulation of MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1 and by Ras. Biochem J., 2004, Jul 15; 381(Pt 2):453-462
  • Ortiz-Vega S., Khokhlatchev A., Nedwidek M., Zhang X.-f., Dammann R., Pfeifer GP., Avruch, J. The Putative Tumor Suppressor RASSF1A Homodimerizes and Heterodimerizes with the Ras-GTP Binding Protein Nore1. Oncogene, 2002, 21 (9) 1381-1390
  • Khokhlatchev A, Xavier R, Rabizadeh S, Nedwidek M, Chen T, Zhang X-f, Seed B, Avruch J. Identification of a novel Ras-regulated proapoptotic pathway. Current Biology, 2002, 12(4) 253-265
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    Contact Information
      Office Address: PO Box 800904, 415 Lane Road, MR5 Building 3133, 
      Office Phone: +1 434-243-2877
      Fax Phone: +1 434-924-2151

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