Biomedical Research Education & Training
Faculty Member

Fesik, Stephen W, Ph.D.
Professor of Biochemistry
Professor of Pharmacology
Professor of Chemistry
Orrin H. Ingram II Chair in Cancer Research

Lab Url:

Phone Number: 615-322-6303

Email Address:

Fesik, Stephen's picture
Academic history
B.A., College of Holy Cross
Ph.D., University of Connecticut
Postdoc, Yale University

Office Address   Mailing Address

634 RRB / 802 RRB

607 Light Hall, 2215 Garland Ave. 37232-0146

Research Keywords
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.

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, 7(10), 3265-74, 2008

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, 105(1), 174-9, 2008 PMCID:2224181

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, 51(21), 6902-15, 2008

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, 14(11), 3268-77, 2008

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, 68(9), 3421-8, 2008

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, 68(18), 7570-8, 2008 PMCID:2597026

Bruncko, M, Oost, TK, Belli, BA, Ding, H, Joseph, MK, Kunzer, A, Martineau, D, McClellan, WJ, Mitten, M, Ng, SC, Nimmer, PM, Oltersdorf, T, Park, CM, Petros, AM, Shoemaker, AR, Song, X, Wang, X, Wendt, MD, Zhang, H, Fesik, SW, Rosenberg, SH, Elmore, SW. Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL. J Med Chem, 50(4), 641-62, 2007

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, 70(1), 1-12, 2007

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, 69(6), 395-404, 2007

Li, L, Lin, X, Khvorova, A, Fesik, SW, Shen, Y. Defining the optimal parameters for hairpin-based knockdown constructs. RNA, 13(10), 1765-74, 2007 PMCID:1986814

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, 26(27), 3972-9, 2007

Morgan-Lappe, SE, Tucker, LA, Huang, X, Zhang, Q, Sarthy, AV, Zakula, D, Vernetti, L, Schurdak, M, Wang, J, Fesik, SW. Identification of Ras-related nuclear protein, targeting protein for xenopus kinesin-like protein 2, and stearoyl-CoA desaturase 1 as promising cancer targets from an RNAi-based screen. Cancer Res, 67(9), 4390-8, 2007

Sarthy, AV, Morgan-Lappe, SE, Zakula, D, Vernetti, L, Schurdak, M, Packer, JC, Anderson, MG, Shirasawa, S, Sasazuki, T, Fesik, SW. Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells. Mol Cancer Ther, 6(1), 269-76, 2007

Tahir, SK, Yang, X, Anderson, MG, Morgan-Lappe, SE, Sarthy, AV, Chen, J, Warner, RB, Ng, SC, Fesik, SW, Elmore, SW, Rosenberg, SH, Tse, C. Influence of Bcl-2 family members on the cellular response of small-cell lung cancer cell lines to ABT-737. Cancer Res, 67(3), 1176-83, 2007

Li, L, Lin, X, Shoemaker, AR, Albert, DH, Fesik, SW, Shen, Y. Hypoxia-inducible factor-1 inhibition in combination with temozolomide treatment exhibits robust antitumor efficacy in vivo. Clin Cancer Res, 12(15), 4747-54, 2006

Morgan-Lappe, S, Woods, KW, Li, Q, Anderson, MG, Schurdak, ME, Luo, Y, Giranda, VL, Fesik, SW, Leverson, JD. RNAi-based screening of the human kinome identifies Akt-cooperating kinases: a new approach to designing efficacious multitargeted kinase inhibitors. Oncogene, 25(9), 1340-8, 2006

Petros, AM, Dinges, J, Augeri, DJ, Baumeister, SA, Betebenner, DA, Bures, MG, Elmore, SW, Hajduk, PJ, Joseph, MK, Landis, SK, Nettesheim, DG, Rosenberg, SH, Shen, W, Thomas, S, Wang, X, Zanze, I, Zhang, H, Fesik, SW. Discovery of a potent inhibitor of the antiapoptotic protein Bcl-xL from NMR and parallel synthesis. J Med Chem, 49(2), 656-63, 2006

Shoemaker, AR, Oleksijew, A, Bauch, J, Belli, BA, Borre, T, Bruncko, M, Deckwirth, T, Frost, DJ, Jarvis, K, Joseph, MK, Marsh, K, McClellan, W, Nellans, H, Ng, S, Nimmer, P, O''Connor, JM, Oltersdorf, T, Qing, W, Shen, W, Stavropoulos, J, Tahir, SK, Wang, B, Warner, R, Zhang, H, Fesik, SW, Rosenberg, SH, Elmore, SW. A small-molecule inhibitor of Bcl-XL potentiates the activity of cytotoxic drugs in vitro and in vivo. Cancer Res, 66(17), 8731-9, 2006

Wendt, MD, Shen, W, Kunzer, A, McClellan, WJ, Bruncko, M, Oost, TK, Ding, H, Joseph, MK, Zhang, H, Nimmer, PM, Ng, SC, Shoemaker, AR, Petros, AM, Oleksijew, A, Marsh, K, Bauch, J, Oltersdorf, T, Belli, BA, Martineau, D, Fesik, SW, Rosenberg, SH, Elmore, SW. Discovery and structure-activity relationship of antagonists of B-cell lymphoma 2 family proteins with chemopotentiation activity in vitro and in vivo. J Med Chem, 49(3), 1165-81, 2006

Fesik, SW. Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer, 5(11), 876-85, 2005

Hajduk, PJ, Huth, JR, Fesik, SW. Druggability indices for protein targets derived from NMR-based screening data. J Med Chem, 48(7), 2518-25, 2005

Oltersdorf, T, Elmore, SW, Shoemaker, AR, Armstrong, RC, Augeri, DJ, Belli, BA, Bruncko, M, Deckwerth, TL, Dinges, J, Hajduk, PJ, Joseph, MK, Kitada, S, Korsmeyer, SJ, Kunzer, AR, Letai, A, Li, C, Mitten, MJ, Nettesheim, DG, Ng, S, Nimmer, PM, O''Connor, JM, Oleksijew, A, Petros, AM, Reed, JC, Shen, W, Tahir, SK, Thompson, CB, Tomaselli, KJ, Wang, B, Wendt, MD, Zhang, H, Fesik, SW, Rosenberg, SH. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature, 435(7042), 677-81, 2005

Park, CM, Sun, C, Olejniczak, ET, Wilson, AE, Meadows, RP, Betz, SF, Elmore, SW, Fesik, SW. Non-peptidic small molecule inhibitors of XIAP. Bioorg Med Chem Lett, 15(3), 771-5, 2005

Huth, JR, Yu, L, Collins, I, Mack, J, Mendoza, R, Isaac, B, Braddock, DT, Muchmore, SW, Comess, KM, Fesik, SW, Clore, GM, Levens, D, Hajduk, PJ. NMR-driven discovery of benzoylanthranilic acid inhibitors of far upstream element binding protein binding to the human oncogene c-myc promoter. J Med Chem, 47(20), 4851-7, 2004

Oost, TK, Sun, C, Armstrong, RC, Al-Assaad, AS, Betz, SF, Deckwerth, TL, Ding, H, Elmore, SW, Meadows, RP, Olejniczak, ET, Oleksijew, A, Oltersdorf, T, Rosenberg, SH, Shoemaker, AR, Tomaselli, KJ, Zou, H, Fesik, SW. Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer. J Med Chem, 47(18), 4417-26, 2004

Petros, AM, Gunasekera, A, Xu, N, Olejniczak, ET, Fesik, SW. Defining the p53 DNA-binding domain/Bcl-x(L)-binding interface using NMR. FEBS Lett, 559(1-3), 171-4, 2004

Petros, AM, Olejniczak, ET, Fesik, SW. Structural biology of the Bcl-2 family of proteins. Biochim Biophys Acta, 1644(2-3), 83-94, 2004

Hajduk, PJ, Mendoza, R, Petros, AM, Huth, JR, Bures, M, Fesik, SW, Martin, YC. Ligand binding to domain-3 of human serum albumin: a chemometric analysis. J Comput Aided Mol Des, 17(2-4), 93-102, 2003

Huang, Q, Petros, AM, Virgin, HW, Fesik, SW, Olejniczak, ET. Solution structure of the BHRF1 protein from Epstein-Barr virus, a homolog of human Bcl-2. J Mol Biol, 332(5), 1123-30, 2003

Liu, G, Szczepankiewicz, BG, Pei, Z, Janowick, DA, Xin, Z, Hajduk, PJ, Abad-Zapatero, C, Liang, H, Hutchins, CW, Fesik, SW, Ballaron, SJ, Stashko, MA, Lubben, T, Mika, AK, Zinker, BA, Trevillyan, JM, Jirousek, MR. Discovery and structure-activity relationship of oxalylarylaminobenzoic acids as inhibitors of protein tyrosine phosphatase 1B. J Med Chem, 46(11), 2093-103, 2003

Szczepankiewicz, BG, Liu, G, Hajduk, PJ, Abad-Zapatero, C, Pei, Z, Xin, Z, Lubben, TH, Trevillyan, JM, Stashko, MA, Ballaron, SJ, Liang, H, Huang, F, Hutchins, CW, Fesik, SW, Jirousek, MR. Discovery of a potent, selective protein tyrosine phosphatase 1B inhibitor using a linked-fragment strategy. J Am Chem Soc, 125(14), 4087-96, 2003

Xiao, Z, Chen, Z, Gunasekera, AH, Sowin, TJ, Rosenberg, SH, Fesik, S, Zhang, H. Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents. J Biol Chem, 278(24), 21767-73, 2003

Yu, L, Oost, TK, Schkeryantz, JM, Yang, J, Janowick, D, Fesik, SW. Discovery of aminoglycoside mimetics by NMR-based screening of Escherichia coli A-site RNA. J Am Chem Soc, 125(15), 4444-50, 2003

Hajduk, PJ, Shuker, SB, Nettesheim, DG, Craig, R, Augeri, DJ, Betebenner, D, Albert, DH, Guo, Y, Meadows, RP, Xu, L, Michaelides, M, Davidsen, SK, Fesik, SW. NMR-based modification of matrix metalloproteinase inhibitors with improved bioavailability. J Med Chem, 45(26), 5628-39, 2002

Huang, Q, Petros, AM, Virgin, HW, Fesik, SW, Olejniczak, ET. Solution structure of a Bcl-2 homolog from Kaposi sarcoma virus. Proc Natl Acad Sci U S A, 99(6), 3428-33, 2002 PMCID:122540

Fesik, SW, Shi, Y. Structural biology. Controlling the caspases. Science, 294(5546), 1477-8, 2001

Liu, G, Huth, JR, Olejniczak, ET, Mendoza, R, DeVries, P, Leitza, S, Reilly, EB, Okasinski, GF, Fesik, SW, von Geldern, TW. Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of inhibition and structure-based improvement of pharmaceutical properties. J Med Chem, 44(8), 1202-10, 2001

Liu, Z, Sun, C, Olejniczak, ET, Meadows, RP, Betz, SF, Oost, T, Herrmann, J, Wu, JC, Fesik, SW. Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain. Nature, 408(6815), 1004-8, 2001

Mao, H, Hajduk, PJ, Craig, R, Bell, R, Borre, T, Fesik, SW. Rational design of diflunisal analogues with reduced affinity for human serum albumin. J Am Chem Soc, 123(43), 10429-35, 2001

Petros, AM, Medek, A, Nettesheim, DG, Kim, DH, Yoon, HS, Swift, K, Matayoshi, ED, Oltersdorf, T, Fesik, SW. Solution structure of the antiapoptotic protein bcl-2. Proc Natl Acad Sci U S A, 98(6), 3012-7, 2001 PMCID:30598

Riedl, SJ, Renatus, M, Schwarzenbacher, R, Zhou, Q, Sun, C, Fesik, SW, Liddington, RC, Salvesen, GS. Structural basis for the inhibition of caspase-3 by XIAP. Cell, 104(5), 791-800, 2001

Fesik, SW. Insights into programmed cell death through structural biology. Cell, 103(2), 273-82, 2000

Hajduk, PJ, Boyd, S, Nettesheim, D, Nienaber, V, Severin, J, Smith, R, Davidson, D, Rockway, T, Fesik, SW. Identification of novel inhibitors of urokinase via NMR-based screening. J Med Chem, 43(21), 3862-6, 2000

Hajduk, PJ, Bures, M, Praestgaard, J, Fesik, SW. Privileged molecules for protein binding identified from NMR-based screening. J Med Chem, 43(18), 3443-7, 2000

Hajduk, PJ, Gomtsyan, A, Didomenico, S, Cowart, M, Bayburt, EK, Solomon, L, Severin, J, Smith, R, Walter, K, Holzman, TF, Stewart, A, McGaraughty, S, Jarvis, MF, Kowaluk, EA, Fesik, SW. Design of adenosine kinase inhibitors from the NMR-based screening of fragments. J Med Chem, 43(25), 4781-6, 2000

Huth, JR, Olejniczak, ET, Mendoza, R, Liang, H, Harris, EA, Lupher, ML, Wilson, AE, Fesik, SW, Staunton, DE. NMR and mutagenesis evidence for an I domain allosteric site that regulates lymphocyte function-associated antigen 1 ligand binding. Proc Natl Acad Sci U S A, 97(10), 5231-6, 2000 PMCID:25811

Losonczi, JA, Olejniczak, ET, Betz, SF, Harlan, JE, Mack, J, Fesik, SW. NMR studies of the anti-apoptotic protein Bcl-xL in micelles. Biochemistry, 39(36), 11024-33, 2000

Sun, C, Cai, M, Meadows, RP, Xu, N, Gunasekera, AH, Herrmann, J, Wu, JC, Fesik, SW. NMR structure and mutagenesis of the third Bir domain of the inhibitor of apoptosis protein XIAP. J Biol Chem, 275(43), 33777-81, 2000

Cai, M, Wang, H, Olejniczak, ET, Meadows, RP, Gunasekera, AH, Xu, N, Fesik, SW. Accurate measurement of H(N)-H(alpha) residual dipolar couplings in proteins. J Magn Reson, 139(2), 451-3, 1999

Hajduk, PJ, Dinges, J, Schkeryantz, JM, Janowick, D, Kaminski, M, Tufano, M, Augeri, DJ, Petros, A, Nienaber, V, Zhong, P, Hammond, R, Coen, M, Beutel, B, Katz, L, Fesik, SW. Novel inhibitors of Erm methyltransferases from NMR and parallel synthesis. J Med Chem, 42(19), 3852-9, 1999

Hajduk, PJ, Meadows, RP, Fesik, SW. NMR-based screening in drug discovery. Q Rev Biophys, 32(3), 211-40, 1999

Hajduk, PJ, Zhou, MM, Fesik, SW. NMR-based discovery of phosphotyrosine mimetics that bind to the Lck SH2 domain. Bioorg Med Chem Lett, 9(16), 2403-6, 1999

Martin, DA, Zheng, L, Siegel, RM, Huang, B, Fisher, GH, Wang, J, Jackson, CE, Puck, JM, Dale, J, Straus, SE, Peter, ME, Krammer, PH, Fesik, S, Lenardo, MJ. Defective CD95/APO-1/Fas signal complex formation in the human autoimmune lymphoproliferative syndrome, type Ia. Proc Natl Acad Sci U S A, 96(8), 4552-7, 1999 PMCID:16370

Sun, C, Cai, M, Gunasekera, AH, Meadows, RP, Wang, H, Chen, J, Zhang, H, Wu, W, Xu, N, Ng, SC, Fesik, SW. NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP. Nature, 401(6755), 818-22, 1999

Betz, SF, Schnuchel, A, Wang, H, Olejniczak, ET, Meadows, RP, Lipsky, BP, Harris, EA, Staunton, DE, Fesik, SW. Solution structure of the cytohesin-1 (B2-1) Sec7 domain and its interaction with the GTPase ADP ribosylation factor 1. Proc Natl Acad Sci U S A, 95(14), 7909-14, 1998 PMCID:20903

Eberstadt, M, Huang, B, Chen, Z, Meadows, RP, Ng, SC, Zheng, L, Lenardo, MJ, Fesik, SW. NMR structure and mutagenesis of the FADD (Mort1) death-effector domain. Nature, 392(6679), 941-5, 1998

Liu, X, Wang, H, Eberstadt, M, Schnuchel, A, Olejniczak, ET, Meadows, RP, Schkeryantz, JM, Janowick, DA, Harlan, JE, Harris, EA, Staunton, DE, Fesik, SW. NMR structure and mutagenesis of the N-terminal Dbl homology domain of the nucleotide exchange factor Trio. Cell, 95(2), 269-77, 1998

Eberstadt, M, Huang, B, Olejniczak, ET, Fesik, SW. The lymphoproliferation mutation in Fas locally unfolds the Fas death domain. Nat Struct Biol, 4(12), 983-5, 1997

Hajduk, PJ, Dinges, J, Miknis, GF, Merlock, M, Middleton, T, Kempf, DJ, Egan, DA, Walter, KA, Robins, TS, Shuker, SB, Holzman, TF, Fesik, SW. NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein. J Med Chem, 40(20), 3144-50, 1997

Hajduk, PJ, Meadows, RP, Fesik, SW. Discovering high-affinity ligands for proteins. Science, 278(5337), 497,499, 1997

Liang, H, Fesik, SW. Three-dimensional structures of proteins involved in programmed cell death. J Mol Biol, 274(3), 291-302, 1997

Minn, AJ, V??lez, P, Schendel, SL, Liang, H, Muchmore, SW, Fesik, SW, Fill, M, Thompson, CB. Bcl-x(L) forms an ion channel in synthetic lipid membranes. Nature, 385(6614), 353-7, 1997

Sattler, M, Liang, H, Nettesheim, D, Meadows, RP, Harlan, JE, Eberstadt, M, Yoon, HS, Shuker, SB, Chang, BS, Minn, AJ, Thompson, CB, Fesik, SW. Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science, 275(5302), 983-6, 1997

Yu, L, Petros, AM, Schnuchel, A, Zhong, P, Severin, JM, Walter, K, Holzman, TF, Fesik, SW. Solution structure of an rRNA methyltransferase (ErmAM) that confers macrolide-lincosamide-streptogramin antibiotic resistance. Nat Struct Biol, 4(6), 483-9, 1997

Huang, B, Eberstadt, M, Olejniczak, ET, Meadows, RP, Fesik, SW. NMR structure and mutagenesis of the Fas (APO-1/CD95) death domain. Nature, 384(6610), 638-41, 1996

Liang, H, Petros, AM, Meadows, RP, Yoon, HS, Egan, DA, Walter, K, Holzman, TF, Robins, T, Fesik, SW. Solution structure of the DNA-binding domain of a human papillomavirus E2 protein: evidence for flexible DNA-binding regions. Biochemistry, 35(7), 2095-103, 1996

Muchmore, SW, Sattler, M, Liang, H, Meadows, RP, Harlan, JE, Yoon, HS, Nettesheim, D, Chang, BS, Thompson, CB, Wong, SL, Ng, SL, Fesik, SW. X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature, 381(6580), 335-41, 1996

Ravichandran, KS, Igras, V, Shoelson, SE, Fesik, SW, Burakoff, SJ. Evidence for a role for the phosphotyrosine-binding domain of Shc in interleukin 2 signaling. Proc Natl Acad Sci U S A, 93(11), 5275-80, 1996 PMCID:39235

Sattler, M, Fesik, SW. Use of deuterium labeling in NMR: overcoming a sizeable problem. Structure, 4(11), 1245-9, 1996

Shuker, SB, Hajduk, PJ, Meadows, RP, Fesik, SW. Discovering high-affinity ligands for proteins: SAR by NMR. Science, 274(5292), 1531-4, 1996

Yu, L, Zhu, CX, Tse-Dinh, YC, Fesik, SW. Backbone dynamics of the C-terminal domain of Escherichia coli topoisomerase I in the absence and presence of single-stranded DNA. Biochemistry, 35(30), 9661-6, 1996

Zhou, MM, Huang, B, Olejniczak, ET, Meadows, RP, Shuker, SB, Miyazaki, M, Tr??b, T, Shoelson, SE, Fesik, SW. Structural basis for IL-4 receptor phosphopeptide recognition by the IRS-1 PTB domain. Nat Struct Biol, 3(4), 388-93, 1996

Harlan, JE, Yoon, HS, Hajduk, PJ, Fesik, SW. Structural characterization of the interaction between a pleckstrin homology domain and phosphatidylinositol 4,5-bisphosphate. Biochemistry, 34(31), 9859-64, 1995

Yu, L, Zhu, CX, Tse-Dinh, YC, Fesik, SW. Solution structure of the C-terminal single-stranded DNA-binding domain of Escherichia coli topoisomerase I. Biochemistry, 34(23), 7622-8, 1995

Zhou, MM, Meadows, RP, Logan, TM, Yoon, HS, Wade, WS, Ravichandran, KS, Burakoff, SJ, Fesik, SW. Solution structure of the Shc SH2 domain complexed with a tyrosine-phosphorylated peptide from the T-cell receptor. Proc Natl Acad Sci U S A, 92(17), 7784-8, 1995 PMCID:41230

Zhou, MM, Ravichandran, KS, Olejniczak, EF, Petros, AM, Meadows, RP, Sattler, M, Harlan, JE, Wade, WS, Burakoff, SJ, Fesik, SW. Structure and ligand recognition of the phosphotyrosine binding domain of Shc. Nature, 378(6557), 584-92, 1995

Hansen, AP, Petros, AM, Meadows, RP, Fesik, SW. Backbone dynamics of a two-domain protein: 15N relaxation studies of the amino-terminal fragment of urokinase-type plasminogen activator. Biochemistry, 33(51), 15418-24, 1994

Hansen, AP, Petros, AM, Meadows, RP, Nettesheim, DG, Mazar, AP, Olejniczak, ET, Xu, RX, Pederson, TM, Henkin, J, Fesik, SW. Solution structure of the amino-terminal fragment of urokinase-type plasminogen activator. Biochemistry, 33(16), 4847-64, 1994

Harlan, JE, Hajduk, PJ, Yoon, HS, Fesik, SW. Pleckstrin homology domains bind to phosphatidylinositol-4,5-bisphosphate. Nature, 371(6493), 168-70, 1994

Liang, H, Mao, X, Olejniczak, ET, Nettesheim, DG, Yu, L, Meadows, RP, Thompson, CB, Fesik, SW. Solution structure of the ets domain of Fli-1 when bound to DNA. Nat Struct Biol, 1(12), 871-5, 1994

Liang, H, Olejniczak, ET, Mao, X, Nettesheim, DG, Yu, L, Thompson, CB, Fesik, SW. The secondary structure of the ets domain of human Fli-1 resembles that of the helix-turn-helix DNA-binding motif of the Escherichia coli catabolite gene activator protein. Proc Natl Acad Sci U S A, 91(24), 11655-9, 1994 PMCID:45290

Logan, TM, Zhou, MM, Nettesheim, DG, Meadows, RP, Van Etten, RL, Fesik, SW. Solution structure of a low molecular weight protein tyrosine phosphatase. Biochemistry, 33(37), 11087-96, 1994

Meadows, RP, Olejniczak, ET, Fesik, SW. A computer-based protocol for semiautomated assignments and 3D structure determination of proteins. J Biomol NMR, 4(1), 79-96, 1994

Petros, AM, Fesik, SW. Nuclear magnetic resonance methods for studying protein-ligand complexes. Methods Enzymol, 239, 717-39, 1994

Yoon, HS, Hajduk, PJ, Petros, AM, Olejniczak, ET, Meadows, RP, Fesik, SW. Solution structure of a pleckstrin-homology domain. Nature, 369(6482), 672-5, 1994

Fesik, SW. NMR structure-based drug design. J Biomol NMR, 3(3), 261-9, 1993

Logan, TM, Olejniczak, ET, Xu, RX, Fesik, SW. A general method for assigning NMR spectra of denatured proteins using 3D HC(CO)NH-TOCSY triple resonance experiments. J Biomol NMR, 3(2), 225-31, 1993

Meadows, RP, Nettesheim, DG, Xu, RX, Olejniczak, ET, Petros, AM, Holzman, TF, Severin, J, Gubbins, E, Smith, H, Fesik, SW. Three-dimensional structure of the FK506 binding protein/ascomycin complex in solution by heteronuclear three- and four-dimensional NMR. Biochemistry, 32(3), 754-65, 1993

Th??riault, Y, Logan, TM, Meadows, R, Yu, L, Olejniczak, ET, Holzman, TF, Simmer, RL, Fesik, SW. Solution structure of the cyclosporin A/cyclophilin complex by NMR. Nature, 361(6407), 88-91, 1993

Xu, RX, Meadows, RP, Fesik, SW. Heteronuclear 3D NMR studies of water bound to an FK506 binding protein/immunosuppressant complex. Biochemistry, 32(10), 2473-80, 1993

Hansen, AP, Petros, AM, Mazar, AP, Pederson, TM, Rueter, A, Fesik, SW. A practical method for uniform isotopic labeling of recombinant proteins in mammalian cells. Biochemistry, 31(51), 12713-8, 1992

Olejniczak, ET, Xu, RX, Fesik, SW. A 4D HCCH-TOCSY experiment for assigning the side chain 1H and 13C resonances of proteins. J Biomol NMR, 2(6), 655-9, 1992

Xu, RX, Olejniczak, ET, Fesik, SW. Stereospecific assignments and chi 1 rotamers for FKBP when bound to ascomycin from 3JH alpha,H beta and 3HN,H beta coupling constants. FEBS Lett, 305(2), 137-43, 1992

Fesik, SW. NMR studies of molecular complexes as a tool in drug design. J Med Chem, 34(10), 2937-45, 1991

Fesik, SW, Gampe, RT, Holzman, TF, Egan, DA, Edalji, R, Luly, JR, Simmer, R, Helfrich, R, Kishore, V, Rich, DH. Isotope-edited NMR of cyclosporin A bound to cyclophilin: evidence for a trans 9,10 amide bond. Science, 250(4986), 1406-9, 1990

Fesik, SW, Zuiderweg, ER. Heteronuclear three-dimensional NMR spectroscopy of isotopically labelled biological macromolecules. Q Rev Biophys, 23(2), 97-131, 1990

Fesik, SW, Zuiderweg, ER, Olejniczak, ET, Gampe, RT. NMR methods for determining the structures of enzyme/inhibitor complexes as an aid in drug design. Biochem Pharmacol, 40(1), 161-7, 1990

Zuiderweg, ER, Fesik, SW. Heteronuclear three-dimensional NMR spectroscopy of the inflammatory protein C5a. Biochemistry, 28(6), 2387-91, 1989

Fesik, SW, Luly, JR, Erickson, JW, Abad-Zapatero, C. Isotope-edited proton NMR study on the structure of a pepsin/inhibitor complex. Biochemistry, 27(22), 8297-301, 1988

Olejniczak, ET, Gampe, RT, Rockway, TW, Fesik, SW. NMR study of the solution conformation of rat atrial natriuretic factor 7-23 in sodium dodecyl sulfate micelles. Biochemistry, 27(18), 7124-31, 1988

Fesik, SW, Bolis, G, Sham, HL, Olejniczak, ET. Structure refinement of a cyclic peptide from two-dimensional NMR data and molecular modeling. Biochemistry, 26(7), 1851-9, 1987

Kohlbrenner, WE, Fesik, SW. Determination of the anomeric specificity of the Escherichia coli CTP:CMP-3-deoxy-D-manno-octulosonate cytidylyltransferase by 13C NMR spectroscopy. J Biol Chem, 260(27), 14695-700, 1985

Postdoctoral Position Available

Postdoctoral Position Details
MOLECULAR BIOLOGIST/ CELL BIOLOGIST to identify and validate new cancer drug targets, clone, express, and purify proteins for screening and structure determination, and develop and perform primary and secondary biological assays.
MEDICINAL CHEMIST to design, synthesize, and optimize small molecules for binding to their target proteins and for their drug-like properties.
STRUCTURAL BIOLOGIST to screen fragment libraries, determine the three-dimensional structures of protein/ligand complexes using NMR spectroscopy and X-ray crystallography, and participate in drug design using molecular modeling techniques.

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