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Anang A. Shelat, PhD
Anang A. Shelat, PhD

Anang A. Shelat, PhD

Associate Member, St. Jude Faculty

  • Director, Lead Discovery Informatics and Compound Management

Departments

Education

BA – Harvard University
PhD
 – University of California, San Francisco, California

Research Interests

  • Translational research in pediatric cancer
  • Development of novel and selective epigenetic drug therapies
  • Targeting the DNA damage response to optimize chemo- and  radiation therapy
  • Multi-scale modeling of biological and chemical data

Selected Publications

Gartrell J, Mellado-Lagarde M, Clay MR, Bahrami A, Sahr NA, Sykes A, Blankenship K, Hoffman L, Xie J, Cho HP, Twarog N, Connelly M, Yan KK, Yu J, Porter SN, Pruett-Miller SM, Neale G, Tinkle CL, Federico SM, Stewart EA, Shelat AA. SLFN11 is widely expressed in pediatric sarcoma and induces variable sensitization to replicative stress caused by DNA damaging agents. Mol Cancer Ther Aug 19;molcanther.MCT-21-0089-A,2021. oi: 10.1158/1535-7163.MCT-21-0089. Online ahead of print.

He C, Xu K, Zhu X, Dunphy PS, Gudenas B, Lin W, Twarog N, Hover LD, Kwon CH, Kasper LH, Zhang J, Li X, Dalton J, Jonchere B, Mercer KS, Currier DG, Caufield W, Wang Y, Xie J, Broniscer A, Wetmore C, Upadhyaya SA, Qaddoumi I, Klimo P, Boop F, Gajjar A, Zhang J, Orr BA, Robinson GW, Monje M, Freeman Iii BB, Roussel MF, Northcott PA, Chen T, Rankovic Z, Wu G, Chiang J, Tinkle CL, Shelat AA, Baker SJ.  Patient-derived models recapitulate heterogeneity of molecular signatures and drug response in pediatric high-grade glioma. Nat Commun Jul 2;12(1):4089, 2021. doi: 10.1038/s41467-021-24168-8.

Twarog NR, Martinez NE, Gartrell J, Xie J, Tinkle CL, Shelat AA. Using response surface models to analyze drug combinations. Drug Discov Today Jun 10;S1359-6446(21)00274-9, 2021. doi: 10.1016/j.drudis.2021.06.002. Online ahead of print. 

Husband HR, Campagne O, He C, Zhu X, Bianski BM, Baker SJ, Shelat AA, Tinkle CL, Stewart CF. Model-based evaluation of image-guided fractionated whole-brain radiation therapy in pediatric diffuse intrinsic pontine glioma xenografts. CPT Pharmacometrics Syst Pharmacol May 3, 2021. doi: 10.1002/psp4.12627. Online ahead of print.  

Nishiguchi G, Das S, Ochoada J, Long H, Lee RE, Rankovic Z, Shelat AA. Evaluating and evolving a screening library in academia: The St Jude approach. Drug Discov Today Jan 14;S1359-6446(21)00005-2, 2021. doi: 10.1016/j.drudis.2021.01.005. Online ahead of print

Federico SM, Pappo AS, Sahr N, Sykes A, Campagne O, Stewart CF, Clay MR, Bahrami A, McCarville MB, Kaste SC, Santana VM, Helmig S, Gartrell J, Shelat A, Brennan RC, Hawkins D, Godwin K, Bishop MW, Furman WL, Stewart E. A phase I trial of talazoparib and irinotecan with and without temozolomide in children and young adults with recurrent or refractory solid malignancies. Eur J Cancer. Sep;137:204-213, 2020. doi: 10.1016/j.ejca.2020.06.014. Epub Aug 11, 2020.

Slavish PJ, Chi L, Yun MK, Tsurkan L, Martinez NE, Jonchere B, Chai SC, Connelly M, Waddell MB, Das S, Neale G, Li Z, Shadrick WR, Olsen RR, Freeman KW, Low JA, Price JE, Young BM, Bharatham N, Boyd VA, Yang J, Lee RE, Morfouace M, Roussel MF, Chen T, Savic D, Guy RK, White SW, Shelat AA, Potter PM. Bromodomain-selective BET inhibitors are potent antitumor agents against MYC-driven pediatric cancer. Cancer Res. 2020 Jul 10;canres.3934.2019. doi: 10.1158/0008-5472.CAN-19-3934. Online ahead of print.

Twarog NR, Connelly M, Shelat AA. A critical evaluation of methods to interpret drug combinations. Sci Rep.  Mar 20;10(1):5144; 2020. doi: 10.1038/s41598-020-61923-1.

Verras A, Waller CL, Gedeck P, Green DV, Kogej T, Raichurkar A, Panda M, Shelat AA, Clark J, Guy RK, Papadatos G, Burrows J. Shared consensus machine learning models for predicting blood stage malaria inhibition. J Chem Inf Model Mar 27;57(3):445-453, 2017. doi: 10.1021/acs.jcim.6b00572. Epub Mar 17, 2017.

Gose T, Shafi T, Fukuda Y, Das S, Wang Y, Allcock A, Gavan McHarg A, Lynch J, Chen T, Tamai I, Shelat A, Ford RC, Schuetz JD. ABCG2 requires a single aromatic amino acid to "clamp" substrates and inhibitors into the binding pocket. FASEB J. Apr;34(4):4890-4903, 2020. doi: 10.1096/fj.201902338RR. Epub Feb 17, 2020

Drenberg CD, Shelat A, Dang J, Cotton A, Orwick SJ, Li M, Jeon JY, Fu Q, Buelow DR, Pioso M, Hu S, Inaba H, Ribeiro RC, Rubnitz JE, Gruber TA, Guy RK, Baker SD. A high-throughput screen indicates gemcitabine and JAK inhibitors may be useful for treating pediatric AML.Nat Commun. May 16;10(1):2189; 2019. doi: 10.1038/s41467-019-09917-0.

Loh A, Bradley C, Karlstrom A, Krafcik F, Dyer MA, Stewart E, Goshorn R, Chen X, Daryani V, Stewart C, Calabrese C, Funk A, Miller G, Shelat A, Bahrami A. Combinatorial screening using orthotopic patient derived xenograft-expanded early phase cultures of osteosarcoma identify novel therapeutic drug combinations. Cancer Lett November 2018.

Stewart E, McEvoy J, Wang H, Chen X, Honnell V, Ocarz M, Gordon B, Dapper J, Blankenship K, Yang Y, Li Y, Shaw TI, Cho JH, Wang X, Xu B, Gupta P, Fan Y, Liu Y, Rusch M, Griffiths L, Jeon J, Freeman BB 3rd, Clay MR, Pappo A, Easton J, Shurtleff S, Shelat A, Zhou X, Boggs K, Mulder H, Yergeau D, Bahrami A,  Mardis ER,  Wilson RK,  Zhang J,  Peng J,  Downing JR,  Dyer MA. Identification of therapeutic targets in rhabdomyosarcoma through integrated genomic,  epigenomic,  and proteomic analyses. Cancer Cell 34(3):411-426.e19, 2018.

Nimmervoll BV, Boulos N, Bianski B, Dapper J, DeCuypere M, Shelat A, Terranova S, Terhune HE, Gajjar A, Patel YT, Freeman BB, Onar-Thomas A, Stewart CF, Roussel MF, Guy RK, Merchant TE, Calabrese C, Wright KD, Gilbertson RJ. Establishing a preclinical multidisciplinary board for brain tumors. Clin Cancer Res 24:1654-1666, 2018.

Bharatham N, Slavish PJ, Young BM, Shelat AA. The role of ZA channel water-mediated interactions in the design of bromodomain-selective BET inhibitors. J Mol Graph Model 81:197-210, 2018.

Shadrick WR, Slavish PJ, Chai SC, Waddell B, Connelly M, Low JA, Tallant C, Young BM, Bharatham N, Knapp S, Boyd VA, Morfouace M, Roussel MF, Chen T, Lee RE, Kiplin Guy R, Shelat AA, Potter PM. Exploiting a water network to achieve enthalpy-driven, bromodomain-selective BET inhibitors. Bioorg Med Chem Nov 4, 2017.

Stewart E, Federico SM, Chen X, Shelat AA, Bradley C, Gordon B, Karlstrom A, Twarog NR, Clay MR, Bahrami A, Freeman BB 3rd, Xu B, Zhou X, Wu J, Honnell V, Ocarz M, Blankenship K, Dapper J, Mardis ER, Wilson RK, Downing J, Zhang J, Easton J, Pappo A, Dyer MA. Orthotopic patient-derived xenografts of paediatric solid tumours. Nature 549(7670):96-100, 2017.

Scott DC, Hammill JT, Min J, Rhee DY, Connelly M, Sviderskiy VO, Bhasin D, Chen Y, Ong SS, Chai SC, Goktug AN, Huang G, Monda JK, Low J, Kim HS, Paulo JA, Cannon JR, Shelat AA, Chen T, Kelsall IR, Alpi AF, Pagala V, Wang X, Peng J, Singh B, Harper JW, Schulman BA, Guy RK. Blocking an N-terminal acetylation-dependent protein interaction inhibits an E3 ligase. Nat Chem Biol 13(8):850-857, 2017.

Smallwood HS, Duan S, Morfouace M, Rezinciuc S, Shulkin BL, Shelat A, Zink EE, Milasta S, Bajracharya R, Oluwaseum AJ, Roussel MF, Green DR, Pasa-Tolic L, Thomas PG. Targeting metabolic reprogramming by influenza infection for therapeutic intervention. Cell Rep 19(8):1640-1653, 2017.

Verras A, Waller CL, Gedneck P, Green DVS, Jogej T, Raichurkar A, Panda M, Shelat AA, Clark J, Guy RK, Papadatos G, Burrows J. Shared consensus machine learning models for predicting blood stage malaria inhibition. J Chem Inf Model 57(3):445-453, 2017.

Twarog NR, Stewart E, Hammill CV, A Shelat A. BRAID: A unifying paradigm for the analysis of combined drug action. Sci Rep 6:25523, 2016.

Stewart E, Federico S, Karlstrom A, Shelat A, Sablauer A, Pappo A, Dyer MA. The childhood solid tumor network: A new resource for the developmental biology and oncology research communities.Dev Biol Apr 9, 2015. Epub ahead of print. pii:S0012-1606(15)00060-3. doi:10.1016/j.ydbio.2015.02.002.

Stewart E, Goshorn R, Bradley C, Griffiths LM, Benavente C, Twarog NR, Miller GM, Caufield W, Freeman BB 3rd, Bahrami A, Pappo A, Wu J, Loh A, Karlstrom A, Calabrese C, Gordon B, Tsurkan L, Hatfield MJ, Potter PM, Snyder SE, Thiagarajan S, Shirinifard A, Sablauer A, Shelat AA, Dyer MA. Targeting the DNA Repair Pathway in Ewing Sarcoma. Cell Rep 9(3):829-840, 2014.

Morfouace M, Shelat A, Jacus M, Freeman BB 3rd, Turner D, Robinson S, Zindy F, Wang YD, Finkelstein D, Ayrault O, Bihannic L, Puget S, Li XN, Olson JM, Robinson GW, Guy RK, Stewart CF, Gajjar A, Roussel MF. Pemetrexed and gemcitabine as combination therapy for the treatment of Group3 medulloblastoma. Cancer Cell 25(4):516-529, 2014.

Chen X, Stewart E, Shelat AA, Qu C, Bahrami A, Hatley M, Wu G, Bradley C, McEvoy J, Pappo A, Spunt S, Valentine MB, Valentine V, Krafcik F, Lang WH, Wierdl M, Tsurkan L, Tolleman V, Federico SM, Morton C, Lu C, Ding L, Easton J, Rusch M, Nagahawatte P, Wang J, Parker M, Wei L, Hedlund E, Finkelstein D, Edmonson M, Shurtleff S, Boggs K, Mulder H, Yergeau D, Skapek S, Hawkins DS, Ramirez N, Potter PM, Sandoval JA, Davidoff AM, Mardis ER, Wilson RK, Zhang J, Downing JR, Dyer MA. Targeting oxidative stress in embryonal rhabdomyosarcoma. Cancer Cell 24(6):710-724, 2013.

Atkinson JM, Shelat AA, Carcaboso AM, Kranenburg TA, Arnold LA, Boulos N, Wright K, Johnson RA, Poppleton H, Mohankumar KM, Feau C, Phoenix T, Gibson P, Zhu L, Tong Y, Eden C, Ellison DW, Priebe W, Koul D, Yung WK, Gajjar A, Stewart CF, Guy RK, Gilbertson RJ. An integrated in vitro and in vivo high-throughput screen identifies treatment leads for ependymoma. Cancer Cell 20(3):384-99, 2011.

Guiguemde WA, Shelat AA, Bouck D, Duffy S, Crowther GJ, Davis PH, Smithson DC, Connelly M, Clark J, Zhu F, Jimenez-Diaz MB, Martinez MS, Wilson EB, Tripathi AK, Gut J, Sharlow ER, Bathurst I, El Mazouni F, Fowble JW, Forquer I, McGinley PL, Castro S, Angulo-Barturen I, Ferrer S, Rosenthal PJ, Derisi JL, Sullivan DJ, Lazo JS, Roos DS, Riscoe MK, Phillips MA, Rathod PK, Van Voorhis WC, Avery VM, Guy RK. Chemical genetics of Plasmodium falciparum. Nature 465(7296):311-5, 2010.

Shelat AA, Guy RK. A road less traveled by: exploring a decade of Ellman chemistry. Bioorg Med Chem 17(3):1088-93, 2009.

Mallari JP, Shelat AA, Obrien T, Caffrey CR, Kosinski A, Connelly M, Harbut M, Greenbaum D, McKerrow JH, Guy RK. Development of potent purine-derived nitrile inhibitors of the trypanosomal protease TbcatB. J Med Chem 51(3):545-52, 2008.

Mallari JP, Shelat A, Kosinski A, Caffrey CR, Connelly M, Zhu F, McKerrow JH, Guy RK. Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB. Bioorg Med Chem Lett 18(9):2883-5, 2008.

Shelat AA, Guy RK. Scaffold composition and biological relevance of screening libraries. Nat Chem Biol 3(8):442-6, 2007.

Shelat AA, Guy RK. The interdependence between screening methods and screening libraries. Curr Opin Chem Biol 11(3):244-51, 2007.

Fujii N, Shelat A, Hall RA, Guy RK. Design of a selective chemical probe for class I PDZ domains. Bioorg Med Chem Lett 17(2):546-8, 2007.

Last update: September 2021