Bin Tean TEH

Chromatin Therapeutics

Profile

Bin Tean TEH
Lab Location: #7-18   Email: btteh@imcb.a-star.edu.sg   Tel: 65869560

Dr Bin Tean Teh obtained his MD (1992) from the University of Queensland, Australia and his PhD (1997) from the Karolinska Institute, Sweden. Following postdoctoral works in multiple endocrine neoplasia 1 at Karolinska Institute, Dr Teh joined the Van Andel Research Institute (VARI) in 2000 as a Senior Scientific Investigator heading the Laboratory of Cancer Genetics. In 2007, Dr Teh was appointed as the founding Director of the National Cancer Centre Singapore (NCCS)-VARI laboratory, which serves as a bridge between translational research and clinical medicine. In 2010 he received the STaR award and relocated to Singapore and is currently a full professor in CSCB. He served as the SingHealth Group Director for Translational Research from 2010-2012. His laboratory focuses on genomic studies of cancers common among Asian populations, using tools such as high-throughput genomic platforms and correlation studies with cliinico-pathological information. He holds Adjunct Professorships at several universities worldwide including Baylor College of Medicine, USA, Nanjing University and Sun Yat-Sen University, China and the Karolinska Institute, Sweden. Dr. Teh has published extensively, with over 300 publications in high impact scientific journals. He has been member of various editorial boards for journals including Lancet Oncology, Cancer Research, Molecular Cancer Therapeutics, International Journal of Oncology, Journal of Clinical Endocrinology and Metabolism, Clinical Genitourinary Cancer, and the American Journal of Translational Research.

Research

Chromatin Therapeutics

We have identified in several cancer types novel frequent mutations in chromatin enzymes. The latter include 1) histone modifiers such asUTX,MLL3,SETD2; 2) subunits of the SWI-SNF complex includingARID1AandPBRM1; and 3) subunit of MEDIATOR complex such asMED12. Athough all these genes are involved in gene regulation, the functional relevance of these mutations in tumorigenesis remains largely unknown. To date, we have established patient-derived cancer cell lines and xenografts harboring these mutations. By combining molecular and structural studies, our laboratory will focus on the studies of novel chromatin drugs to help elucidate the roles of these enzymes and their dysregulation in tumorigenesis. Our ultimate goal is to bring this new interesting group of drugs, either as monotherapy or combination therapy, to clinical use.

Figure Legend:Somatic mutations inARID1Aand the suppressive role ofARID1Ain cholangiocarcinoma cell proliferation.(a)Distribution ofARID1Amutations identified in all cohorts of samples. ARID, AT-rich interactive domain; LXXLL, C-terminal leucine-rich LXXLL motif.(b)Relative proliferation of cell lines H69, EGI-1 and M139 (wild-typeARID1A) depleted of endogenousARID1AusingARID1A-specific (siARID1A_3) compared to control siRNA.(c)Relative proliferation of the same cell lines exogenously transfected with vector expressing wild-typeARID1A(pCGT-ARID1A) or empty vector (mock).


Publications


Lim WK, Ong CK, Tan J, Thike AA, Ng CC, Rajasegaran V, Myint SS, Nagarajan S, Nasir ND, McPherson JR, Cutcutache I, Poore G, Tay ST, Ooi WS, Tan VK, Hartman M, Ong KW, Tan BK, Rozen SG, Tan PH, Tan P,Teh BTExome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma.
Nature Genet46(8): 877–880, 2014

Chan-on W, Nairismägi M-L, Ong CK, Dima S, Pairojkul C, Lim KH, McPherson JR, Lim WK, Cucutache I, Heng HL, Ooi L, Chung A, Chow P, Cheow PC, Lee SY, Huat ITB, Duda D, Nastase A, Myint SS, Wong BH, Gan A, Rajasegaran V, Ng CCY, Jusakul A, Zhang S, Vohra P, Yu W, Huang D, Yongvanit P, Wongkham S, Khuntikeo N, Bhudhisawasdi V, Popescu I, Rozen SG, Tan P,Teh BT. 2013.
Distinct mutational patters of infection and non-infection-related bile duct cancers revealed by exome sequencing.
Nature Genet.45(12): 1474–1478

Poon SL, Pang ST, McPherson JR, Yu W, Huang KK, Guan P, Weng WH, Siew EY, Liu Y, Heng HL, Chong SC, Gan A, Tay ST, Lim WK, Cutcutache I, Huang D, Ler LD, Nairismägi ML, Lee MH, Chang YH, Yu KJ, Chan-on W, Li BK, Yuan YF, Qiang CN, Ng KF, Wu CF, Hsu CL, Bunte RM, Stratton MR, Futureal PA, Sung WK, Chuang CK, Ong CK, Rozen SG, Tan P,Teh BT.2013.
Genome-wide mutational signatures of aristolochic acid and its application as a screening tool.
Sci Transl Med5(197): 197ra 101.(Received Journal Cover Image and Focus Article, also highlighted by Nature Genetis, Science Magazine)

Koo GC, Tan SY, Tang T, Poon SL, Allen GE, Tan L, Chong SC, Ong WS, Tay K, Tao M, Quek R, Loong S, Yeoh KW, Yap SP, Lee KA, Lim LC, Tan D, Goh C, Cutcutache I, Yu W, Ng CCY , Rajasegaran V, Heng HL, Gan A, Ong CK, Rozen S, Tan P,Teh BT, Lim ST. 2012.
Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma.
Cancer Discov2(7): 591–597.

Ong CK, Subimerb C, Pairojkul C, Wongkham S, Cutcutache I, Yu W, McPherson J, Allen GE, Ng CCY, Wong BHM, Myint SS, Rajasegaran V, Heng HL, Gan A, Zang ZJ, Wu Y, Wu J, Lee MH, Huang D, Ong P, Chan-on W, Cao Y, Qian CN, Lim KH, Ooi A, Dykema KJ, Furge K, Kukongviriyapan V, Sripa B, Wongkham C, Yongvanit P, Futreal PA, Bhudhisawasdi V, Rozen S, Tan P,Teh BT. 2012.
Exome sequencing of liver fluke-associated cholangiocarcinoma.
Nat Genet44(6): 690–693.

Zang ZJ, Cutcutache I, Poon SL, Zhang SL, McPherson J, Tao J, Rajasegaran V, Heng HL, Deng N, Gan A, Lim KH, Ong CK, Huang D, Chin SY, Tan IB, Ng CCY, Yu W, Wu Y, Lee M, Wu J, Poh D, Wan WK, Rha SY, So J, Salto-Tellez M, Yeoh KG, Wong WK, Futreal PA, Pang B, Ruan Y, Hillmer A, Bertrand D, Nagarajan N, Rozen S,Teh BT*, Tan P.
Exome sequencing of gastric adenocarcinoma reveals recurrent somatic mutations in cell adhesion and chromatin remodeling genes.
Nat Genet44(5): 570-574, 2012

Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, Davies H, Jones D, Lin M-L, Teague J, Bignell G, Butler A, Cho J, Dalgliesh GL, Galappaththige D, Greenman C, Hardy C, Jia M, Latimer C, Lau KW, Marshall J, McLaren S, Menzies A, Mudie L, Stebbings L, Largaespada DA, Wessels LFA, Richard S, Kahnoski RJ, Anema J, Tuveson D, Perez-Mancera P, Mustonen V, Fischer A, Adams DJ, Rust A, Chan-on W, Subimerb C, Dykema K, Furge K, Campbell PJ,Teh BT, Stratton MR, Futreal PA. 2011.
Exome sequencing identifies frequent mutation of the SWI/SNF complex genePBRM1in renal carcinoma.
Nature2011: 469(7331): 539–542. PMCID: PMC3030920(Co-corresponding author)

Ooi A, Wong J-C, Petillo D, Roossien D, Perrier-Trudova V, Whitten D, Hui Min BW, Tan M-H, Zhang Z, Yang XJ, Zhou M,Gardie B, Molinie V, Richard S, Tan PH,Teh BT, Furge KA. 2011.
An antioxidant response phenotype shared between hereditary and sporadic type 2 papillary renal cell carcinoma.
Cancer Cell20(4): 511–523.*Highlighted in Cancer Cell Previews 20(4): 418–420, 2011, Nature Reviews Cancer 11, 2011; and Nature Chemical Biology January 2012

Dalgliesh GL, Furge K, Greenman C, Chen L, Bignell G, Butler A, Davies H, Edkins S, Hardy C, Latimer C, Teague J, Andrews J, Barthorpe S, Beare D, Buck G, Campbell PJ, Forbes S, Jia M, Jones D, Knott H, Kok CY, Lau KW, Leroy C, Lin ML, McBride DJ, Maddison M, Maquire S, McLay K, Menzies A, Mironenko T, Mulderrig L, Mudie L, O’Meara S, Pleasance E, Rajasingham A, Shepherd R, Smith R, Stebbings L, Stephens P, Tang G, Tarpety PS, Turrell K, Dykema KJ, Khoo SK, Petillo D, Wondergem B, Anema J, Kahnoski RJ,Teh BT, Stratton MR, Futreal PA. 2010. Systemic sequencing of renal cell carcinoma reveals inactivation of histone modifying genes.
Nature463(7279): 360–363. PMCID: PMC2820242(Co-corresponding author)

Van Haaften G, Dalgliesh GL, Davies H, Bigness G, Greenman C, Edkins S, Hardy C, O’Meara S, Chen L, Teague J, Butler A, Hinton J, Tofts C, Andrews J, Barthorpe S, Beare D, Buck G, Campbell PJ, Cole J, Dunmore R, Forbes S, Jia M, Jones D, Kok CY, Leroy C, Lin M-L, McBride DJ, Maddison M, Maquire S, Menzies A, Mironenko T, Mulderrig L, Mudie L, Pleasance E, Shepherd R, Smith R, Stebbings L, Stephens P, Tan G, Tarpey PS, Turner R, Turrell K, Varian J, West S, Widaa S, Wray P, Collins VP, Ichimura K, Law S, Wong J, Yuen ST, Leung SY, Tonon G, DePinho RA, Tai Y-T, Anderson KC, Kahnoski RJ, Massie A, Khoo SK,Teh BT, Stratton MR, Futreal PA. 2009.
Somatic mutations of the histone H3K27 demethylase,UTX, in human cancer.
Nature Genet41(5): 521–523. PMCID: 2873835