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PHS 398/2590 (Rev. 06/09), Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Emine Ercikan Abali Associate Professor of Biochemistry, eRA COMMONS USER NAME (credential, e.g., agency login) Pharmacology and Medicine ABALIEM EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.) INSTITUTION AND LOCATION DEGREE MM/YY FIELD OF STUDY (if applicable) University of Southwestern Louisiana, Lafayette, LA B.Sc. 1982-1986 Chemistry University of Southwestern Louisiana, Lafayette, LA M.S. 1988-1988 Chemistry The Ohio State University, Columbus, OH Ph.D. student 1989-1990 Chemistry Cornell University Graduate School of Medical Ph.D. 1990-1996 Pharmacology Sciences and Memorial Sloan Kettering Cancer Center, New York, NY Memorial Sloan Kettering Cancer Center, NY, NY Postdoc 1996-1998 Molecular Therapeutics Columbia University, NY, NY Postdoc 1998-1999 Biological Sciences (10months) A. Personal Background The overall aim of this project is to use dihydrofolate reductase (DHFR) as a prototype for other NAD(P) binding dehydrogenases to identify novel NAD(P) analogues that specifically target the NADPH binding site of DHFR as potent inhibitors of cancer cells. Specifically, we plan to investigate metabolism of NADPS in cell lines and in xenograft animal and to perform in silico screening of the NADPH binding site to identify potential new inhibitors targeted to DHFR. Lastly, we will determine further characterize the mechanism of action of NADPS in accelerating the degradation of DHFR in order to address development of drug-resistance to this new class of inhibitors. I have the expertise, leadership and enthusiasm to be in charge of determining the metabolism of NADPS and studying the mechanism of degradation of NADPS. My research area over the years focused on antifolate metabolism specifically to MTX, inhibitor of dihydrofolate reductase. I have successfully lead Dr. Bertino’s project as a Co-PI in his previous R01 grants and trained many undergraduate, graduate students and postdoctoral fellows. Dr. Bertino (PI), Banerjee (Investigator) and I (Co-PI) have worked together over many projects and our publication record is a testimony for our successful collaborations. Our on-going research builds logically to the hypotheses to be tested in the proposed project. B. Positions and Honors Positions and Employment Visiting Assistant Professor, Department of Molecular Biology and Genetics 1999-2001 Bilkent University, Turkey Assistant Professor, Department of Medicine and Pharmacology 2002-2009 The Cancer Institute of New Jersey, RWJMS-UMDNJl Associate Professor of Biochemistry, RWJMS-UMDNJ 2009-present Other Experience and Professional Memberships Member, American Medical Biochemistry Course Directors Member, Scientific Review Board of CINJ, RWJMS, UMDNJ Member, Cancer Institute of New Jersey Member, Graduate School of Biomedical Sciences, UMDNJ-RUTGERS Associate member of the Cellular and Molecular Pharmacology Graduate Program, UMDNJ PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): Member of American Association for Cancer Research Member of AACR-Women in Cancer Research Member of RNA society Member of American Society of Biochemistry and Molecular Biology Honors Department of Medicine Grant Award 2005 Cancer Institute of New Jersey New Investigator Award 2002 Faculty Development Award, Bilkent University, Turkey 2000 American Association for Cancer Research-Bristol-Mayers-Young Investigator Award 1998 American Association for Cancer Research-Young Investigator from Pharmingen 1997 American Association for Cancer Research Travel Award from Roche 1996 Fulbright scholarship 1982-1986 Alpha Delta Kappa-International Teaching Scholarship 1982-1985 C. Selected Peer-reviewed Publications Most relevant to the current application 1. Ercikan, E.A., Waltham, M., Dicker, A.P., Schweitzer, B., Bertino, J.R. (1993) Effect of codon 22 mutations on substrate and inhibitor binding for human dihydrofolate reductase. Adv Exp Med Biol. 338, 515-519. 2. Ercikan, E.A., Banerjee, D., Waltham, M., Schneiders, B., Scotto, K., Bertino, J.R. (1993) Translational regulation of the synthesis of dihydrofolate reductase. Adv Exp Med Biol. 338, 537-540. 3. Rosowsky, A., Mota, C.E., Queener, S.F., Waltham, M., Ercikan, E.A., Bertino, J.R. (1995) 2,4- Diamino-5-substituted-quinazolines as inhibitors of a human dihydrofolate reductase with a site- directed mutation at position 22 and of the dihydrofolate reductases from Pneumocystis carinii and Toxoplasma gondii. J Med Chem. 38, 745-52. 4. Banerjee, D., Ercikan Abali, E.A., Waltham, M., Schneiders, B., Hochhauser, D., Li, W.W., Fan, J., Gorlick, R., Goker, E., Bertino, J.R. (1995) Molecular mechanisms of resistance to antifolates, a review. Acta Biochim Pol. 42, 457-464. 5. Ercikan Abali, E.A., Waltham, M., Dicker, A.P., Gritsman, H., Banerjee, D., Bertino, J.R. (1996) Variants of human dihydrofolate reductase with substitutions at leucine-22: effect on catalytic and inhibitor binding properties. Mol Pharmacol. 49, 430-437. 6. Hochhauser, D., Schneiders, B., Ercikan Abali, E.A., Gorlick, R., Muise-Helmericks, R., Li, W.W., Fan, J., Banerjee, D., Bertino, J.R. (1996) Effect of cyclin D1 overexpression on drug sensitivity in a human fibrosarcoma cell line. J Natl Cancer Inst. 88, 1269-1275. 7. Ercikan Abali, E.A., Mineishi, S., Nakahara, S., Tong, Y., Waltham, M.C., Chen, W., Banerjee, D., Bertino, J.R. (1996) Active site-directed double mutants of dihydrofolate reductase. Cancer Res. 56, 4142-4145. 8. Longo, G.S., Gorlick, R., Tong, W.P., Ercikan E, Bertino, J.R. (1997) Disparate affinities of antifolates for folylpolyglutamate synthetase from human leukemia cells. Blood 90, 1241-1245. 9. Ercikan Abali, E.A., Banerjee, D., Waltham, M.C., Scotto, K., Bertino, J.R. (1997) Dihydrofolate reductase protein inhibits its own translation by binding to dihydrofolate reductase mRNA sequences within the coding region. Biochemistry 36, 12317-12322. 10. Tong, Y., Liu-Chen, X., Ercikan Abali, E.A., Zhao, S.C., Banerjee, D., Bertino, J.R. (1998) Isolation and characterization of thymitaq (AG337) and 5-fluoro-2-deoxyuridylate-resistant mutants of human thymidylate synthase from ethyl methanesulfonate-exposed human sarcoma HT1080 cells. J Biol Chem. 273, 11611-11618. 11. Tong, Y., Liu-Chen, X., Ercikan Abali, E.A., Zhao, S.C., Banerjee, D., Maley, F., Bertino, J.R. (1998) Probing the folate-binding site of human thymidylate synthase by site-directed mutagenesis. Generation of mutants that confer resistance to raltitrexed, Thymitaq, and BW1843U89. J Biol Chem. ;273, 31209-31214. 12. Banerjee D., Tong, Y., Liu-Chen, X., Capiaux, J.R., Ercikan Abali, E., Takebe, N., O'Connor, O.A., Bertino, J.R. (1999) Protection of bone marrow cells from toxicity of chemotherapeutic agents PHS 398/2590 (Rev. 06/09) Page Continuation Format Page Program Director/Principal Investigator (Last, First, Middle): targeted toward thymidylate synthase by transfer of mutant forms of human thymidylate synthase cDNA. Gene Therapy: Bertino J.R. (ed.) Prog Exp Tumor Res. Basel, Karger 36, 107-114. 13. Bertino, J.R., Zhao, S.C., Mineishi, S., Ercikan Abali E., Banerjee D. (1999) Use of variants of dihydrofolate reductase in gene transfer to produce resistance to methotrexate and trimetrexate. Gene Therapy: Bertino J.R. (ed.) Prog Exp Tumor Res. Basel, Karger 36, 82-94. 14. Ural, A.U., Takebe, D., Adhikari, D., Ercikan-Abali, E., Banerjee, D., Barakat, R, Bertino, J.R. (2000) Gene Therapy for Endometrial Carcinoma with the Herpes Simplex Thymidine Kinase Gene. Gynecol Oncol. 76(3), 305-310. ¹MANDATORY REPATRIATION TO MEET HER OBLIGATIONNS FOR FULBRIGHT SCHOLARSHIP FROM 1999-2001¹ 15. Skacel N, Menon LG, Prasunkumar J. Misra, Peters R, Scotto, KW, Banerjee D, Bertino JR and Ercikan-Abali,E. (2005) Identification of amino acids required for the functional upregulation of human dihydrofolate reductase protein in response to antifolate treatment. J Biol Chem. 280 (24), 22721- 22731. 16. Ercikan Abali E, Skacel N, Menon LG, Mishra PJ, Banerjee D and Bertino JR (2007) Mechanism of Upregulation of Dihydrofolate Reductase” In: Peters GJ, Jansen G, eds. Chemistry and Biology of Pteridines and Folates Heilbronn: SPS Verlagsgesellschaft, 105-118.4. 17. Yi-Ching Hsieh, Nancy Skacel, Nitu Bansal, Kathleen Scotto, Debabrata Banerjee,Joseph R. Bertino and Emine Ercikan Abali. Species Specific Differences in Translational Regulation of Dihydrofolate Reductase. Mol Pharmacol. 2009 76(4):723-33.2. Invited Articles (Reviews, Editorials, etc.) In Journals; Chapters; Books; other Professional Communication 1. Ercikan Abali, E, Skacel, NE, Celikkaya, H, Hsieh YC. (2008) Regulation of Human Dihydrofolate Reductase Activity and Expression . Vitam. Horm. 79,267-292. C. Research Support. On-going Research Support- None Completed Research Support. 15 R01 CA 08010-41 (Co-PI) 12/1/2004-11/30/2009 NCI Mechanism of action of folate antagonists. This grant supports mechanism of action studies of folate inhibitors of dihydrofolate reductase and thymidylate synthase Department of Medicine Research Grant-RWJMS-UMDNJ (PI) 2005-2006 Mechanism of Translational Regulation of Dihydrofolate Reductase Type-Research
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