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RESEARCH FOCUS
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The main research interest of my lab is to understand which and how genetic variants influence disease development. Currently, there are three main research programs in the lab focusing on breast cancer, Parkinson’s disease and schizophrenia.
Breast Cancer
Genetic factors are important for breast cancer development, but known disease genes can only explain a partial of its familial risk. By collaborating with Karolina Institute at Sweden and Helsinki University at Finland, we are now working on a project to understand the genetic basis of breast cancer development. Given the important role of sex hormone exposure in breast and endometrial cancer development, one research focus is to understand how genetic variation within estrogen-related pathways can modify sex hormone-related risk to these two cancers. Complementary to our hypothesis-driven study, we are also actively involved in genome-wide association study (GWAS) on both breast cancer susceptibility and prognosis. This program is currently funded by A*STAR as well as an external grant (R01) from the National Institute of Health, USA.
Neurological and psychiatric Disorders
By collaborating with research groups and clinicians in Singapore, the lab is actively involved in the studies to understand the genetic basis of neurological and psychiatric disorders with a focus on Parkinson’s disease (PD) and schizophrenia. For example, we have done a series of genetic analysis of LRRK2 gene to demonstrate the clinical significance of LRRK2 mutations in Asian PD patients. The lab is now working on a candidate gene-based study to identify novel susceptibility genes for PD as well as a project to understand the pathogenic mechanism of PD-related disease mutations using animal models.
The lab has recently started a new research project to carry out a comprehensive genetic study of schizophrenia and its neurocognitive phenotypes in Singapore population. The project is a part of a national research program on neuroscience that was established through a consortium among Institute of Mental Healthy (IMH), Genome Institute of Singapore (GIS), Duke-National University of Singapore Graduate Medical School (Duke-GMS), Duke University and University of Melbourne. This national effort is a bench-to-bedside research program with the objective to identify key genetic, biological, cognitive and social risk factors and new treatments for schizophrenia and related psychotic disorders. The program is funded as one of five Translational and Clinical Research (TCR) Flagship Programs by Singapore government.
Genetic Analysis of Regulatory Variation
It has been long suggested that regulatory variation plays an important role in phenotypic evolution and disease development, but biological understanding of such variation is very limited. The rapid technological development has made it feasible to identify regulatory sequences at a genome-wide scale and thus to pursue a large-scale genetic and molecular study of their germ-line variation. To take an advantage of the rapidly expanding information on genome-wide transcription factor (TF) binding sequences at GIS, we have initiated a project to understand the role of germ-line variation within TF binding sequences in disease development.
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EDUCATION
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| 1991-1997 | Ph.D., Quantitative Genetics, Duke University, Durham, NC, USA.
| | 1986-1989 | M.S., Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, Chandong, PR China
| | 1981-1986 | B.S., Biology, University of Science & Technology of China, Hefei, Anhui, China
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PROFESSIONAL APPOINTMENTS
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| 2007- | Group Leader, Human Genetics, Genome Institute of Singapore, A*STAR, Singapore |
| 2006- | Adjunct Associate Professor, School of Computer Engineering, Nanyang Technological University, Singapore |
| 2005 - | Adjunct Associated Professor, Centre for Molecular Epidemiology, National University of Singapore, Singapore |
| 2003-2004 | Adjunct Research Fellow, Centre for Molecular Epidemiology, National University of Singapore, Singapore |
| 2002-2006 | Senior Research Scientist, Population Genetics, Genome Institute of Singapore, A*STAR, Singapore |
| 2000-2002 | 2000-2002 Research Scientist, Columbia Genome Center, Columbia University, New York, NY, USA |
| 1998-2000 | Research Scientist in Molecular Genetics, New York State Psychiatric Institute, New York, NY, USA
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| 1997-2000 | Postdoctoral Research Fellow, Columbia Genome Center and Department of Psychiatry, College Physicians and Surgeons at Columbia University, New York, NY, USA
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| 1989-1991 | Research Assistant, Institute of Oceanology, Chinese Academy of Science, Qingdao, China
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HONORS AND AWARDS
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| 2008-2013 | TCR Grant, NMRC, Singapore, “Vulnerability, Disease Progression, and Treatment in Schizophrenia and Related Psychoses”, Co-PI |
| 2005-2010 | R01 Grant, NIH/NCI, USA, “Genetic Determinants of Postmenopausal Sporadic Breast Cancer”, Co-Investigator |
| 2005-2007 | Research Grant, Biomedical Research Council of Singapore, A*STAR, “Haplotype Tagging Analysis in Parkinson’s Disease”, Co-Principal Investigator |
| 2004-2006 | Research Grant, Susan G Koman Breast Cancer Foundation (US), “Genetically determined hormone influence and risk for sporadic breast cancer among postmenopausal women”, Co-investigator |
| 2004-2006 | Research Grant, National Medical Research Council of Singapore, “Pharmacogenetics of tardive dyskinesia”, Co-Principal Investigator |
| 2004-2006 | Research Grant, National Medical Research Council of Singapore, “A case-control study of genes affecting homocysteine metabolism in Singaporean stroke patients”, Collaborator |
| 2000-2001 | Young Investigator Award, Cure Autism Now Foundation
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| 1999-2000 | Young Investigator Award, National Alliance For Research On Schizophrenia and Depression
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| 1998-2000 | Training Grant, New York State Psychiatric Institute
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| 1991 | Fellowship, Duke University
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COMMITTEE AND ADVISORY BOARD
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| 2003 | Member, Domain-Specific Review Board C, National Health Group, Singapore |
| 2002 | Member, Peripheral, Central, Sensory & Cellular Nervous System/Mental Health Subcommittee, National Medical Research Council, Singapore |
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SELECTED PUBLICATIONS
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1. Bei JX, Li Y, Jia WH, Feng BJ, Zhou G, Chen LZ, Feng QS, Low HQ, Zhang H, He F, Tai ES, Kang T, Liu ET, Liu J, Zeng YX "A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci." Nat Genet 2010 Jul ; 42(7) : 599-603 Epub 2010 May 30
Abstract
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2. Low YL, Li Y, Humphreys K, Thalamuthu A, Li Y, Darabi H, Wedrén S, Bonnard C, Czene K, Iles MM, Heikkinen T, Aittomäki K, Blomqvist C, Nevanlinna H, Hall P, Liu ET, Liu J "Multi-variant pathway association analysis reveals the importance of genetic determinants of estrogen metabolism in breast and endometrial cancer susceptibility." PLoS Genet 2010 ; 6 : 001012 Epub 2010 Jul 1
Abstract
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3. Sheng D, Qu D, Kwok KH, Ng SS, Lim AY, Aw SS, Lee CW, Sung WK, Tan EK, Lufkin T, Jesuthasan S, Sinnakaruppan M, Liu J "Deletion of the WD40 domain of LRRK2 in Zebrafish causes Parkinsonism-like loss of neurons and locomotive defect." PLoS Genet 2010 ; 6(4) : e1000914 Epub 2010 Apr 22
Abstract
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4. Zhang Xue-Jun, Huang Wei, Yang Sen, Sun Liang-Dan, Zhang Feng-Yu, Zhu Qi-Xing, Zhang Fu-Ren, Zhang Chi, Du Wen-Hui, Pu Xiong-Ming, Li Hui, Xiao Feng-Li, Wang Zai-Xing, Cui Yong, Hao Fei, Zheng Jie, Yang Xue-Qin, Cheng Hui, He Chun-Di, Liu Xiao-Ming, Xu Li-Min, Zheng Hou-Feng, Zhang Shu-Mei, Zhang Jian-Zhong, Wang Hong-Yan, Cheng Yi-Lin, Ji Bi-Hua, Fang Qiao-Yun, Li Yu-Zhen, Zhou Fu-Sheng, Han Jian-Wen, Quan Cheng, Chen Bin, Liu Jun-Lin, Lin Da, Fan Li, Zhang An-Ping, Liu Sheng-Xiu, Yang Chun-Jun, Wang Pei-Guang, Zhou Wen-Ming, Lin Guo-Shu, Wu Wei-Dong, Fan Xing, Gao Min, Yang Bao-Qi, Lu Wen-Sheng, Zhang Zheng, Zhu Kun-Ju, Shen Song-Ke, Li Min, Zhang Xiao-Yan, Cao Ting-Ting, Ren Wei, Zhang Xin, He Jun, Tang Xian-Fa, Lu Shun, Yang Jian-Qiang, Zhang Lin, Wang Dan-Ni, Yuan Feng, Yin Xian-Yong, Huang Hong-Jie, Wang Hai-Feng, Lin Xin-Yi, Liu Jian-Jun "Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21." Nat. Genet. 2009 Feb ; 41(2) : 205-10
Abstract
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5. Zhang FR, Huang W, Chen SM, Sun LD, Liu H, Li Y, Cui Y, Yan XX, Yang HT, Yang RD, Chu TS, Zhang C, Zhang L, Han JW, Yu GQ, Quan C, Yu YX, Zhang Z, Shi BQ, Zhang LH, Cheng H, Wang CY, Lin Y, Zheng HF, Fu XA, Zuo XB, Wang Q, Long H, Sun YP, Cheng YL, Tian HQ, Zhou FS, Liu HX, Lu WS, He SM, Du WL, Shen M, Jin QY, Wang Y, Low HQ, Erwin T, Yang NH, Li JY, Zhao X, Jiao YL, Mao LG, Yin G, Jiang ZX, Wang XD, Yu JP, Hu ZH, Gong CH, Liu YQ, Liu RY, Wang DM, Wei D, Liu JX, Cao WK, Cao HZ, Li YP, Yan WG, Wei SY, Wang KJ, Hibberd ML, Yang S, Zhang XJ, Liu JJ "Genomewide association study of leprosy." N Engl J Med 2009 Dec 31 ; 361(27) : 2609-18 Epub 2009 Dec 16
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6. Han JW, Zheng HF, Cui Y, Sun LD, Ye DQ, Hu Z, Xu JH, Cai ZM, Huang W, Zhao GP, Xie HF, Fang H, Lu QJ, Xu JH, Li XP, Pan YF, Deng DQ, Zeng FQ, Ye ZZ, Zhang XY, Wang QW, Hao F, Ma L, Zuo XB, Zhou FS, Du WH, Cheng YL, Yang JQ, Shen SK, Li J, Sheng YJ, Zuo XX, Zhu WF, Gao F, Zhang PL, Guo Q, Li B, Gao M, Xiao FL, Quan C, Zhang C, Zhang Z, Zhu KJ, Li Y, Hu DY, Lu WS, Huang JL, Liu SX, Li H, Ren YQ, Wang ZX, Yang CJ, Wang PG, Zhou WM, Lv YM, Zhang AP, Zhang SQ, Lin D, Li Y, Low HQ, Shen M, Zhai ZF, Wang Y, Zhang FY, Yang S, Liu JJ, Zhang XJ "Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus." Nat Genet 2009 Nov ; 41(11) : 1234-7 Epub 2009 Oct 18
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7. Chen J, Zheng H, Bei JX, Sun L, Jia WH, Li T, Zhang F, Seielstad M, Zeng YX, Zhang X, Liu J "Genetic structure of the Han Chinese population revealed by genome-wide SNP variation." Am J Hum Genet 2009 Dec ; 85(6) : 775-85 Epub 2009 Nov 26
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8. Li Y, Sung WK, Liu J. Association Mapping via Regularized Regression Analysis of SNP Haplotypes in Variable-sized Sliding Windows. Am J Hum Genet 2007 80(4):705-15
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9. DF Easton et al. Genome-wide association study identifies breast cancer susceptibility loci. Nature 2007, 447(7148):1087-93.
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10. Jianjun LIU, J Ott, the AGRE Consortium, J Hoh, P Iversen, C Lord, D Geschwind, P Pavone, E Parano, P Magnussen, D. Nyholt, TC Gilliam (2001) "A Genome-wide Screen for Autism Susceptibility Loci" Am. J. Hum. Genet. 69 327-340
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