Stephen W. Fesik, Ph.D.
- Orrin H. Ingram, II Professor of Cancer Research
- Professor of Biochemistry, Pharmacology and Chemistry
Phone
634 RRB, 2200 Pierce Ave
Nashville, TN 37232-0146
Stephen W. Fesik, Ph.D.
- Orrin H. Ingram, II Professor of Cancer Research
- Professor of Biochemistry, Pharmacology and Chemistry
615-322-6303
stephen.fesik@vanderbilt.edu
634 RRB, 2200 Pierce Ave
Nashville, TN 37232-0146
Research Program
Departments/Affiliations
Profile
Stephen W. Fesik, Ph.D. is the Orrin H. Ingram, II Chair in Cancer Research and a Professor of Biochemistry, Pharmacology, and Chemistry in Vanderbilt University School of Medicine. He is also a member of the Vanderbilt Ingram Cancer Center (VICC), the Vanderbilt Institute of Chemical Biology (VICB) and the Center for Structural Biology (CSB).
The focus of his research is on cancer drug discovery using fragment-based approaches and structure-based drug design. Prior to joining Vanderbilt in May, 2009, Dr. Fesik was the Divisional Vice President of Cancer Research at Abbott (2000-2009) where he built a pipeline of compounds that are showing promising anti-cancer activities in early stage clinical trials. In addition, while he was at Abbott, he developed several new NMR methods, determined the three-dimensional structures of several proteins and protein/ligand complexes, pioneered a method for drug discovery called SAR by NMR, and applied this method to identify and optimize ligands for binding to many protein drug targets.
His research has also involved the use of siRNA for target identification and target validation. Dr. Fesik has published more than 240 papers, trained 36 postdoctoral fellows, has been a reviewer for the NIH Biophysical Chemistry Study Section, and has served as a member of the Editorial Boards of the Journal of Medicinal Chemistry, Journal of Biomolecular NMR, Biophysical Journal, Molecular Cell, Chemical Biology & Drug Design, ChemMedChem, Molecular Cancer Therapeutics, Oncogene, Combinatorial Chemistry and High Throughput Screening, and the Highlights Advisory Panel for Nature Reviews Cancer. He has served on the Keystone Scientific Advisory Board and Board of Directors and currently is a member of the Scientific Advisory Board of the UPenn Abramson Cancer Center, Aileron Therapeutics, and the Bruker Board of Directors. He has obtained several awards, including the Chairman’s Award (1996), Outstanding Researcher of the Year Award (1997) , and the Researcher of the Year Team Award (2008) from Abbott, the Servier Lecturer Award (1998) from the University of Montreal, the ASBMB-Fritz Lipmann Lectureship Award (1999), the Lifetime Achievement Award in Nuclear Magnetic Resonance from EAS (2003), the SBS Technology Innovation Award (2010), and the NIH Director's Pioneer Award (2010). Recently he has been elected Fellow of the American Association for the Advancement of Science (AAAS).
Education
- Ph.D., University of Connecticut, Storrs, Connecticut (1981)
- B.A., College of the Holy Cross, Worcester, Massachusetts (1975)
Research Emphasis
Cancer drug discovery, fragment-based drug design, NMR, protein structure, RNAi
Research Description
The focus of our lab is on cancer drug discovery using fragment-based approaches and structure-based design. To accomplish this goal, we have assembled a multidisciplinary team that includes structural biologists, medicinal chemists, and cell biologists. Among them are five research professors and several research assistants, postdoctoral fellows, and graduate students. In our lab, we clone, express, and purify proteins, conduct fragment-based screens, determine the three-dimensional structures of protein/ligand complexes using NMR and/or X-ray crystallography, design and synthesize compounds, and test compounds in primary and secondary biological assays. The cancer drug targets that we are pursuing are highly validated but technically challenging such as K-Ras and c-Myc.
Publications
- Park CM, Bruncko M, Adickes J, Bauch J, Ding H, Kunzer A, Marsh KC, Nimmer P, Shoemaker AR, Song X, Tahir SK, Tse C, Wang X, Wendt MD, Yang X, Zhang H, Fesik SW, Rosenberg SH, Elmore SW. Discovery of an orally bioavailable small molecule inhibitor of prosurvival B-cell lymphoma 2 proteins. J. Med. Chem [print-electronic]. 2008 Nov 11/13/2008; 51(21): 6902-15. PMID: 18841882, DOI: 10.1021/jm800669s, ISSN: 1520-4804.
- Ackler S, Xiao Y, Mitten MJ, Foster K, Oleksijew A, Refici M, Schlessinger S, Wang B, Chemburkar SR, Bauch J, Tse C, Frost DJ, Fesik SW, Rosenberg SH, Elmore SW, Shoemaker AR. ABT-263 and rapamycin act cooperatively to kill lymphoma cells in vitro and in vivo. Mol. Cancer Ther. 2008 Oct; 7(10): 3265-74. PMID: 18852130, PII: 7/10/3265, DOI: 10.1158/1535-7163.MCT-08-0268, ISSN: 1535-7163.
- Zheng M, Morgan-Lappe SE, Yang J, Bockbrader KM, Pamarthy D, Thomas D, Fesik SW, Sun Y. Growth inhibition and radiosensitization of glioblastoma and lung cancer cells by small interfering RNA silencing of tumor necrosis factor receptor-associated factor 2. Cancer Res. 2008 Sep 9/15/2008; 68(18): 7570-8. PMID: 18794145, PMCID: PMC2597026, PII: 68/18/7570, DOI: 10.1158/0008-5472.CAN-08-0632, ISSN: 1538-7445.
- Shoemaker AR, Mitten MJ, Adickes J, Ackler S, Refici M, Ferguson D, Oleksijew A, O'Connor JM, Wang B, Frost DJ, Bauch J, Marsh K, Tahir SK, Yang X, Tse C, Fesik SW, Rosenberg SH, Elmore SW. Activity of the Bcl-2 family inhibitor ABT-263 in a panel of small cell lung cancer xenograft models. Clin. Cancer Res. 2008 Jun 6/1/2008; 14(11): 3268-77. PMID: 18519752, PII: 14/11/3268, DOI: 10.1158/1078-0432.CCR-07-4622, ISSN: 1078-0432.
- Tse C, Shoemaker AR, Adickes J, Anderson MG, Chen J, Jin S, Johnson EF, Marsh KC, Mitten MJ, Nimmer P, Roberts L, Tahir SK, Xiao Y, Yang X, Zhang H, Fesik S, Rosenberg SH, Elmore SW. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008 May 5/1/2008; 68(9): 3421-8. PMID: 18451170, PII: 68/9/3421, DOI: 10.1158/0008-5472.CAN-07-5836, ISSN: 1538-7445.
- Lin X, David CA, Donnelly JB, Michaelides M, Chandel NS, Huang X, Warrior U, Weinberg F, Tormos KV, Fesik SW, Shen Y. A chemical genomics screen highlights the essential role of mitochondria in HIF-1 regulation. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2008 Jan 1/8/2008; 105(1): 174-9. PMID: 18172210, PMCID: PMC2224181, PII: 0706585104, DOI: 10.1073/pnas.0706585104, ISSN: 1091-6490.
- Li L, Lin X, Khvorova A, Fesik SW, Shen Y. Defining the optimal parameters for hairpin-based knockdown constructs. RNA [print-electronic]. 2007 Oct; 13(10): 1765-74. PMID: 17698642, PMCID: PMC1986814, PII: rna.599107, DOI: 10.1261/rna.599107, ISSN: 1355-8382.
- Huth JR, Park C, Petros AM, Kunzer AR, Wendt MD, Wang X, Lynch CL, Mack JC, Swift KM, Judge RA, Chen J, Richardson PL, Jin S, Tahir SK, Matayoshi ED, Dorwin SA, Ladror US, Severin JM, Walter KA, Bartley DM, Fesik SW, Elmore SW, Hajduk PJ. Discovery and design of novel HSP90 inhibitors using multiple fragment-based design strategies. Chem Biol Drug Des. 2007 Jul; 70(1): 1-12. PMID: 17630989, PII: JPP535, DOI: 10.1111/j.1747-0285.2007.00535.x, ISSN: 1747-0277.
- Lin X, Morgan-Lappe S, Huang X, Li L, Zakula DM, Vernetti LA, Fesik SW, Shen Y. 'Seed' analysis of off-target siRNAs reveals an essential role of Mcl-1 in resistance to the small-molecule Bcl-2/Bcl-XL inhibitor ABT-737. Oncogene [print-electronic]. 2007 Jun 6/7/2007; 26(27): 3972-9. PMID: 17173063, PII: 1210166, DOI: 10.1038/sj.onc.1210166, ISSN: 0950-9232.
- Lerner CG, Hajduk PJ, Wagner R, Wagenaar FL, Woodall C, Gu YG, Searle XB, Florjancic AS, Zhang T, Clark RF, Cooper CS, Mack JC, Yu L, Cai M, Betz SF, Chovan LE, McCall JO, Black-Schaefer CL, Kakavas SJ, Schurdak ME, Comess KM, Walter KA, Edalji R, Dorwin SA, Smith RA, Hebert EJ, Harlan JE, Metzger RE, Merta PJ, Baranowski JL, Coen ML, Thornewell SJ, Shivakumar AG, Saiki AY, Soni N, Bui M, Balli DJ, Sanders WJ, Nilius AM, Holzman TF, Fesik SW, Beutel BA. From bacterial genomes to novel antibacterial agents: discovery, characterization, and antibacterial activity of compounds that bind to HI0065 (YjeE) from Haemophilus influenzae. Chem Biol Drug Des. 2007 Jun; 69(6): 395-404. PMID: 17581233, PII: JPP521, DOI: 10.1111/j.1747-0285.2007.00521.x, ISSN: 1747-0277.
