AREA OF INTEREST: BIOTECH/PHARMACEUTICAL/GOVERNMENT SECTOR

QUALIFICATIONS SUMMARY

A highly talented scientist with proven ability to discover things, analyze data, suggest hypothesis, design experiments to test this hypothesis, organize others to do these experiments, check-up progress, troubleshoot, change hypothesis after the analysis of data from experiments, as well as write scientific papers and reports

Excellent publication record, with two Cell papers and other publications in high-profiled journals

Experienced in Signal Transduction, Protein kinases, signaling by Ras oncogene products, Tumor Suppression and some in Microtubule Cytoskeleton

Offering excellent communication, management, and planning skills; able to work either in groups or independently with minimum supervision and work effectively across disciplinary boundaries

Creative, inventive, and analytical who is adept at identifying problems and finding solutions in areas outside formal education, job training, or present focus

Understands the importance of giving credits to all contributors of a successful project, and capable of communicating material recommendations to people inside and outside the organization

A US citizen with proper documents who can work without delay

EXPERTISE

Signal Transduction

 Gel electrophoresis, Western blotting, immunoprecipitation, tissue culture, transfection, retrovirus and lentivirus production, work with radioactive isotopes such as P-32, S-35, etc

Molecular biology

 Cloning in E. coli, DNA manipulations, PCR, mutagenesis, DNA sequence analysis, design of oligonucleotides, expression constructs, shRNAs and vectors

Microscopy

 Immunocytochemistry, light and immunofluorescent microscopy, digital image acquisition, image processing

Protein kinases

 In vitro kinase assays, expression and purification of inactive and active (phosphorylated) forms of kinases from recombinant sources, kinase activation and deactivation in vitro. My Ph. D. thesis was on MAP kinases.

Microinjections of DNA and proteins into living cells

Work with proteins

 Protein expression in E. coli, protein purification by low-pressure column chromatography, HPLC and FPLC, protein-protein interactions.

Animal work

 Tumor growth in athymic mice, rabbit immunization and serum production

EDUCATION

HARVARD MEDICAL SCHOOL BOSTON, MA

 Post-Doctoral in Cancer Biology and Signal Transduction (Mentor: Dr. Joseph Avruch)

UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER  DALLAS, TX

 Doctor of Philosophy in Cell Regulation and Signal Transduction (Mentor: Dr. Melanie Cobb)

MOSCOW STATE UNIVERSITY MOSCOW, USSR

 Master of Science in Biochemistry

EXPERIENCE

UNIVERSITY OF VIRGINIA HEALTH SYSTEM CHARLOTTESVILLE, VA

Assistant Professor (Department of Pathology)2003-Present

• Provide scientific leadership and manage a group of 1-2 Ph.D. scientists and 1 technician, the group are conducting independent research of a novel growth and tumor suppressor protein NORE1A and its relatives

• Participate in undergraduate/graduate student and postdoctoral training, including teaching an advanced graduate course in Cell Signaling

HARVARD MEDICAL SCHOOL AND MASSACHUSETTS GENERAL HOSPITAL  BOSTON, MA

Postdoctoral Fellow and Research Fellow in Medicine 1998-2003

• Examined functions of the NORE1A protein, the MST1 protein kinase that binds it, and the regulation of the NORE1A/MST complex by the Ras oncogene product.

UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER AT DALLAS  DALLAS, TX

Postdoctoral Fellow (Department of Pharmacology) 1997-1998

Graduate Student Research Assistant II (Department of Pharmacology) 1993-1997

• Studied nuclear translocation of the active form of the MAP kinase ERK2.

Research Associate (Department of Molecular Genetics) 1991-1993

INSTITUTE OF BIOORGANIC CHEMISTRY USSR ACADEMY OF SCIENCE  MOSCOW, USSR

Research Trainee/Research Fellow 1984-1991

INVITED SEMINARS

“Growth Suppression by NORE1A, a RASSF Family Member Protein” May 11, 2007. Department of Biology, City of Hope, Duarte, California.

“Mechanisms of Growth and Tumor Suppression by NORE1A, a RASSF Family Member Protein" October 19, 2007, Department of Biology, University of Toledo, Toledo, OH.

“Functions of NORE1A, THE OTHER Ras effector” Department of Pathology, University of Virginia, April 29, 2008

PATENTS/LICENSES

Khokhlatchev, A. The 10F10 monoclonal antibody against human NORE1A protein. A license issued to Upstate Biotechnology, Inc. (currently Millipore) in 2004; additional licenses were issued to Santa Cruz Biotechnology in 2007 and to Cell Signaling in 2008. Royalties from this project were partially used to support the research.

Khokhlatchev, A. and Cobb, M. H. Generation of Active Forms of MAP Kinase Module Enzymes by Coexpression of Two or Three Protein Kinases in Bacteria. A license issued to Roche Bioscience in 1996.

AFFILIATIONS

The American Society for Cell Biology (ASCB), Member: Since 2008

American Association for Cancer Research (AACR), Member: Since 2004

AWARDS

THE LEUKEMIA & LYMPHOMA SOCIETY

Postdoctoral Fellowship

MOSCOW STATE UNIVERSITY MOSCOW, USSR

Graduated cum laude (Department of Biology)

SELECTED PUBLICATIONS

Kuznetsov S and Khokhlatchev, AV. The growth and tumor suppressors NORE1A and RASSF1A are targets for calpain-mediated proteolysis. PLoS ONE. 2008;3(12):3997. Epub 2008 Dec 22.

o My laboratory discovered that NORE1A and RASSF1A proteins might be proteolyzed by calpains in human tumors and tumor cell lines.

Stieglitz B., Bee C., Schwarz D., Yildiz Ö., Moshnikova A., Khokhlatchev, AV. and Herrmann C. Novel type of Ras effector interaction established between tumor suppressor NORE1A and Ras switch II. EMBO Journal, 2008 Jul 23;27(14):1995-2005.

o In collaboration with Dr. C. Herrmann (University of Bohum, Germany) we found what is the structural basis of NORE1A binding to activate Ras.

Moshnikova A., Frye J., Shay J. W., Minna J. D., Khokhlatchev, AV. The growth and tumor suppressor NORE1A is a cytoskeletal protein that suppresses growth by inhibition of the ERK pathway. J. Biol. Chem., 2006, Mar 24, 281(12): 8143-52.

o Discovered that NORE1A is a centrosomal protein with some ability to interact with microtubules. Mapped NORE1A growth-suppressive domain and showed that it could inhibit ERK2 protein kinase activity in some cell systems. The studies suggested a mechanism of NORE1A activation by Ras.

Khokhlatchev, AV., 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.

o Discovered that NORE1A and RASSF1A proteins interact with the pro-apoptotic protein Kinase MST1. The NORE1A-MST1 complex interacts with activated Ras oncogene product and might mediate apoptotic effect of Ras.

o This paper was accompanied by an editorial by Larry Feig and Rachel Buchsbaum (http://www.cell.com/current-biology/retrieve/pii/S096098220200787X - aff2#aff2): “Cell signaling: life or death decisions of ras proteins” Current Biology, Vol. 12, R259–R261, April 2, 2002.

Khokhlatchev, AV., Canagarajah, B., Wilsbacher, J., Robinson, M., Atkinson, M., Goldsmith, E. J., and Cobb, M. H. Phosphorylation of the MAP Kinase ERK2 promotes its homodimerization and nuclear translocation. Cell, 1998, 93 (4): 605-615.

o Discovered that phosphorylated, active ERK2 protein Kinase forms dimers and that the dimerization induces ERK nuclear translocation. Found that related Kinases, JNK and p38 MAPK, are also capable of forming dimers.

Khokhlatchev, AV., Xu, S., English, J., Wu, P., Schaefer, E., Cobb, M. H. Reconstitution of Mitogen-activated Protein Kinase Phosphorylation Cascades in Bacteria: Efficient synthesis of Active Protein Kinases. J. Biol. Chem., 1997, 272: 110**-*****.

o Developed a method how to produce active, doubly phosphorylated MAP Kinases in bacteria, a method that was licensed to Roche.

Canagarajah, B., Khokhlatchev, AV., Cobb, M. H., Goldsmith, E. J. Activation mechanism of the MAP Kinase ERK2 by dual phosphorylation. Cell 1997, 90(5): 859-869.

o The bacterial coexpression method, which was described in the previous paper, allowed to produce active ERK2 in sufficient quantities for crystal structure determination.

ORAL PRESENTATIONS

National and International Conferences

“Identification of the Aurora A Kinase as an interacting partner for the growth and tumor suppressor NORE1A”. Minisymposium session "Cellular and Molecular Biology 69" April 16, 2008 at the 2008 American Association of Cancer Research (AACR) Annual Meeting in San Diego, CA.

“Interaction of the RASSF Family Growth and Tumor Suppressor NORE1A with Microtubules and Centrosomes”, presented at the Second International Conference “Mechanisms and Models of Cancer”, La Jolla, CA, August 12, 2007.

TEACHING

“Advanced Topics and Technologies in Cell Signaling”, Spring 2007 semester, together with Dr. Janet Cross. University of Virginia BIMS862, 3.0 Credit hours.

RESEARCH GRANDS AND AWARDS

Concern Foundation, Khokhlatchev (PI) 07/01/08-06/30/09 with the successful competitive renewal for 07/01/09-06/30/10.

Regulation of the Aurora-A kinase by growth and tumor suppressor NORE1A: 2008-2009: Total Direct Costs $50,000; 2009-2010: Total Direct Costs $50,000

o Principal Investigator (PI) of this project, which intended to determine functional consequences of interaction of NORE1A with Aurora-A kinase in tumor cells and in vitro.

Elsa U. Pardee Foundation, Khokhlatchev (PI): 2007-2008

Function of the NORE1A tumor suppressor in lung cancerogenesis. Total Direct Costs $65,685

o This project is to determine the consequences of NORE1A inactivation for development of transformed phenotype in a genetically defined cell system, human bronchial epithelial cells.

Jeffries Memorial Trust Award J-787, Khokhlatchev (PI): 2006

Determine tumor suppressive capabilities of Ras effector NORE1A in athymic mice. Total Direct Costs $24,000.

o This project is to determine tumor-suppressive capabilities of NORE1A and some of its mutants in athymic mice. Role: PI

Wendy Will Case Cancer Fund, Khokhlatchev (PI): 2006

Mechanisms of NORE1A tumor suppression. Total Direct Cost $25,000

o This project is to perform structure-functional studies of NORE1A and characterize NORE1A mutants deficient in growth suppression. Role: PI

American Cancer Society Institutional Research Grant GF10574, Khokhlatchev (PI): 2003-2004

Total Direct Cost $15,000

o This award supports initial steps of the creation of a conditional knockout NORE1A mouse model.

Research and Development Committee UVa School of Medicine 123214, Khokhlatchev (PI): 5/15/05- 5/14/06.

Determine the functional significance of NORE1A phosphorylation induced by activated Ras and protein Kinase responsible for it. Total Direct Cost $25,000.

o This project is to determine the functional significance of NORE1A phosphorylation at Ser258 induced by activated Ras and identifies the protein kinase responsible for it. Role: PI

ACTIVITIES

Ad hoc reviewer for Journals: Biochemistry, BBRC, FEBS letters, International Journal of Cancer, Journal of Respiratory and Critical Care Medicine, Molecular Cancer Research, and Oncogene

Ad hoc reviewer for Online: Molecule Pages for the UCSD (Nature Signaling Gateway)

Ad hoc reviewer for Cancer Research UK (British Charity)

Dissertation Committees -Served as an outside expert on the Ph. D. Dissertation Committee for Limin Liu, Department of Biology, City of Hope, Duarte, California. (May 2007)

OTHER SKILLS

Languages: English and Russian (Native)

Computer: MS Word, PowerPoint, Excel, Adobe Photoshop; IPLab (special program for image acquisition using high-powered microscope), PDRAW32 and Seqweb (special programs for analysis of DNA sequences); and Internet Explorer

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