Taosheng Chen, PhD, PMP
Taosheng Chen, PhD, PMP

Taosheng Chen, PhD, PMP

Member, St. Jude Faculty

  • Director, High Throughput Bioscience Center

Departments

Education

PhD – University of Vermont
MS – Fudan University, Shanghai
BS – Fudan University, Shanghai

Research Interests

  • Regulation of PXR and CAR (nuclear receptors), and CYP3A (drug–metabolizing enzymes) in drug toxicity, drug resistance and human diseases
  • Development of chemical probes and therapeutic leads for PXR, CAR and CYP3A
  • Development of drug discovery technologies
  • High throughput screening (HTS) and high content screening (HCS)

Selected Publications

Zheng JH, Grace CR, Guibao CD, McNamara DE, Llambi F, Wang YM, Chen T, Moldoveanu T. Intrinsic instability of BOK enables membrane permeabilization in apoptosis. Cell Rep 23(7):2083-2094, 2018.

Buchman CD, Chai SC, Chen T. A current structural perspective on PXR and CAR in drug metabolism. Expert Opin Drug Metab Toxicol 14(6):635-647, 2018.

Cherian MT, Chai SC, Wright WC, Singh A, Casal MA, Zheng J, Wu J, Lee RE, Griffin PR, Chen T. CINPA1 binds directly to constitutive androstane receptor and inhibits its activity. Biochem Pharmacol 152:211-223, 2018.

Teitz T, Fang J, Goktug AN, Bonga JD, Diao S, Hazlitt RA, Iconaru L, Morfouace M, Currier D, Zhou Y, Umans RA, Taylor MR, Cheng C, Min J, Freeman B, Peng J, Roussel MF, Kriwacki R, Guy RK, Chen T, Zuo J. CDK2 inhibitors as candidate therapeutics for hearing loss. J Exp Med 215(4):1187-1203, 2018.

Pitre A, Ge Y, Lin W, Wang Y, Fukuda Y, Temirov J, Phillips AH, Peters JL, Fan Y, Ma J, Nourse A, Sinha C, Lin H, Kriwacki R, Downing JR, Gruber TA, Centonze VE, Naren AP, Chen T, Schuetz JD. An unexpected protein interaction promotes drug resistance in leukemia. Nat Commun 8:1547, 2017.

Oladimeji P, Chen T. PXR: more than just a master xenobiotic receptor. Mol Pharmacol 93(2):119-127, 2018.

Lin W, Wang Y-M, Chai SC, Lv L, Zheng J, Wu J, Zhang Q, Wang Y-D, Griffin PR, Chen T. SPA70 is a potent antagonist of human pregnane X receptor. Nat Commun 8:741, 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 13:850-857, 2017.

Yang J, Milasta S, Hu D, AlTahan AM, Interiano RB, Zhou J, Davidson J, Low J, Lin W, Bao J, Goh P, Nathwani AC, Wang R, Wang Y, Ong SS, Boyd VA, Young B, Das S, Shelat A, Wu Y, Li Z, Zheng JJ,  Mishra A, Cheng Y, Qu C, Peng J, Green DR, White S, Guy RK, Chen T, Davidoff AM. Targeting histone demethylases in MYC-driven neuroblastomas with ciclopirox. Cancer Res 77:4626-4638, 2017.

Oladimeji P, Lin W, Brewer CT, Chen T. Glucose-dependent regulation of pregnane X receptor is modulated by AMP-activated protein kinase. Sci Rep 7:46751, 2017.

Lolodi O, Wang YM, Wright WC, Chen T. Differential regulation of CYP3A4 and CYP3A5 and its implication in drug discovery. Curr Drug Metab 18(12):1095-1105, 2017.

Cherian MT, Yang L, Chai SC, Lin W, Chen T. Identification and characterization of CINPA1 metabolites facilitates structure-activity studies of the constitutive androstane receptor. Drug Metab Dispos 44(11):1759-1770, 2016.

Sprowl JA, Ong SS, Gibson AA, Hu S, Du G, Lin W, Li L, Bharill S, Ness RA, Stecula A, Offer SM, Diasio RB, Nies AT, Schwab M, Cavaletti G, Schlatter E, Ciarimboli G, Schellens JH, Isacoff EY, Sali A, Chen T, Baker SD, Sparreboom A, Pabla N. A phosphotyrosine switch regulates organic cation transporters. Nat Commun 7:10880, 2016.

LIambi F, Wang YM, Victor B, Yang M, Schneider DM, Gingras S, Parsons MJ, Zheng JH, Brown SA, Pelletier S, Moldoveanu T, Chen T,  Green DR. BOK is a non-canonical BCL-2 family effector of apoptosis regulated by ER-associated degradation. Cell 165:421-433, 2016.

Banerjee M, Chai SC, Wu J, Robbins D, Chen T. Tryptophan 299 is a conserved residue of human pregnane X receptor critical for the functional consequence of ligand binding. Biochem Pharmacol 104:131-138, 2016.

Lin W, Yang L, Chai SC, Lu Y, Chen T. Development of CINPA1 analogs as novel and potent inverse agonists of constitutive androstane receptor. Eur J Med Chem 108:505-528, 2016.

Zimmerman EI, Gibson AA, Hu S, Vasilyeva A, Orwick SJ, Du G, Mascara GP, Ong SS, Chen T, Vogel P, Inaba H, Maitland ML, Sparreboom A, Baker SD. Multikinase inhibitors induce cutaneous toxicity through OAT6-mediated uptake and MAP3K7-driven cell death. Cancer Res 76:117-126, 2016.

Rodriguez DA, Weinlich R, Brown S, Guy C, Fitzgerald P, Dillon CP, Oberst A, Quarato G, Low J, Cripps JG, Chen T, Green DR, Characterization of RIPK3-mediated phosphorylation of the activation loop of MLKL during necroptosis. Cell Death Differ 23:76-88, 2016.

Chai SC, Cherian MT, Wang Y, Chen T. Small-molecule modulators of PXR and CAR. Biochim Biophys Acta 1859:1141-1154, 2016.

Churchman ML, Low J, Qu C, Paietta EM, Kasper LH, Chang Y, Payne-Turner D, Althoff MJ, Song G, Chen SC, Ma J, Rusch M, McGoldrick D, Edmonson M, Gupta P, Wang YD, Caufield W, Freeman B, Li L, Panetta JC, Baker S, Yang YL, Roberts KG, McCastlain K, Iacobucci I, Peters JL, Centonze VE, Notta F, Dobson SM, Zandi S, Dick JE, Janke L, Peng J, Kodali K, Pagala V, Min J, Mayasundari A, Williams RT, Willman CL, Rowe J, Luger S, Dickins RA, Guy RK, Chen T, Mullighan CG. Efficacy of retinoids in IKZF1-mutated BCR-ABL1 acute lymphoblastic leukemia. Cancer Cell 28:343-356, 2015.

Wang Y, Chai SC, Lin W, Chai X, Elias A, Wu J, Ong SS, Pondugula SR, Beard JA, Schuetz EG, Zeng S, Xie W, Chen T. Serine 350 of human pregnane X receptor is crucial for its heterodimerization with retinoid X receptor alpha and transactivation of target genes in vitro and in vivo. Biochem Pharmacol 96:357-368, 2015.

Pabla N, Gibson AA, Buege M, Ong SS, Li L, Hu S, Du G, Sprowl JA, Vasilyeva A, Janke LJ, Schlatter E, Chen T, Ciarimboli G, Sparreboom A, Mitigation of acute kidney injury by cell-cycle inhibitors that suppress both CDK4/6 and OCT2 functions. Proc Natl Acad Sci U S A. 112:5231-5236, 2015.

Cherian MT, Lin W, Wu J, Chen T. CINPA1 is an inhibitor of constitutive androstane receptor (CAR) that does not activate pregnane X receptor (PXR). Mol Pharmacol 87(5):878-889, 2015.

Leung W-H, Vong QP, Lin W, Bouck D, Wendt S, Sullivan E, Li Y, Bari R, Chen T, Leung W. PRL-3 mediates the protein maturation of ULBP2 by regulating the tyrosine phosphorylation of HSP60. J Immunol 194:2930-2941, 2015.

Banerjee M, Robbins D, Chen T. Targeting xenobiotic receptors PXR and CAR in human diseases. Drug Discov Today 20:618-628, 2015.

Lin W, Liu J, Jeffries C, Yang L, Lu Y, Lee RE, Chen T. Development of BODIPY FL vindoline as a novel and high-affinity pregnane X receptor fluorescent probe. Bioconjug Chem 25:1664-1677, 2014.

Ong SS, Goktug AN, Elias A, Wu J, Saunders D, Chen T. Stability of the human pregnane X receptor is regulated by E3 ligase UBR5 and serine/threonine kinase DYRK2. Biochem J 459:193-203, 2014.

Elias A, High AA, Mishra A, Ong SS, Wu J, Peng J, Chen T. Identification and characterization of phosphorylation sites within the pregnane X receptor protein. Biochem Pharmacol 87:360-370, 2014.

Leung WH, Vong QP, Lin W, Janke L, Chen T, Leung W. Modulation of NKG2D ligand expression and metastasis in tumors by spironolactone via RXRγ activation. J Exp Med 210:2675-2692, 2013.

Wang YM, Lin W, Chai SC, Wu J, Ong SS, Schuetz EG, Chen T. Piperine activates human pregnane X receptor to induce the expression of cytochrome P450 3A4 and multidrug resistance protein 1. Toxicol Appl Pharmacol 272:96-107, 2013.

Show More

McCoy F, Darbandi R, Lee HC, Bharatham K, Moldoveanu T, Royappa G, Dodd K, Lin W, Chen SI, Tangallapally RP, Kurokawa M, Lee RE, Shelat A, Chen T, Green DR, Harris RA, Lin SH, Fissore RA, Colbran RJ, Nutt LK. Metabolic activation of CaMKII by Coenzyme A. Mol Cell 52:325-339, 2013.

Elias A, Wu J, Chen T. Tumor suppressor protein p53 negatively regulates human pregnane X receptor activity. Mol Pharmacol 83(6):1229-1236, 2013.

Chen T. Overcoming drug resistance by regulating nuclear receptors. Adv Drug Deliv Rev 62:1257-1264, 2010.

Chen T, “A Practical Guide to Assay Development and High-Throughput Screening in Drug Discovery” (T. Chen, ed.), CRC Press, Taylor & Francis Group, Boca Raton, FL, ISBN 978-1-4200-7050-7, 2010.

Mu Q, Du G, Chen T, Zhang B, Yan B. Suppression of human bone morphogenetic protein signaling by carboxylated single-walled carbon nanotubes. ACS Nano 3:1139-1144, 2009.

Lin W, Wu J, Dong H, Bouck D, Zeng FY, Chen T. Cyclin-dependent kinase 2 negatively regulates human pregnane X receptor-mediated CYP3A4 gene expression in HepG2 liver carcinoma cells. J Biol Chem 283:30650-30657, 2008.

Chen T. Nuclear receptor drug discovery. Curr Opin Chem Biol 12:418-426, 2008.

Pondugula PR, Flannery PC, Apte U, Babu JR, Geetha T, Rege SD, Chen T, Abbott KL. PPM1A phosphatase is involved in regulating PXR-mediated CYP3A4 gene expression. Drug Metab Dispos Jan 5, 2015. Epub ahead of print. pii: dmd.114.062083.

Banerjee M, Robbins D, Chen T. Targeting xenobiotic receptors PXR and CAR in human diseases. Drug Discov Today 20(5):618-28, 2014. pii: S1359-6446(14)00456-5. doi: 10.1016/j.drudis.2014.11.011.  

Beard JA, Tenga A, Chen T. The interplay of NR4A receptors and the oncogene–tumor suppressor networks in cancer. Cell Signal 27(2):257-66, 2014. pii: S0898-6568(14)00355-6. doi: 10.1016/j.cellsig.2014.11.009.

Wang YM, Chai SC, Brewer CT, Chen T. Pregnane X receptor and drug-induced liver injury. Expert Opin Drug Metab Toxicol 10(11):1521-32, 2014. doi:10.1517/17425255.2014.963555. 

Last update: July 2018