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Human and Molecular Genetics Research Programme

 

Research Theme

 

  • To unravel the underlying genetic mechanisms of human diseases. The areas of research include genetics of asthma, cardiovascular diseases, developmental disorders, endocrine & metabolic disorders, hematological & oncological disorders, neuromuscular disorders and renal disorders.
  • To develop and establish expertise in animal models of human development and disease, functional genomics, gene mapping by linkage analysis, gene therapy, genetic epidemiology, karyotyping, molecular diagnostics and pharmacogenomics.
  • To maintain a cord blood bank resource representative of Singapore's three major ethnic groups.
  • To provide population-based genetics data and resource for gene and disease mapping
  • To study polymorphisms and explain the variable penetrance of podocyte mutations in patients with nephrotic syndrome enabling nephrologist to identify at-risk patients.

 

Research Areas

 

  • Molecular and clinical methods necessary for a clinical trial with donor-derived T cells directed at differences in patient-individual hematopoiesis-SNPs as treatment for high risk leukaemia and relapse after allergenic SCT.
  • Whole genome association and candidate pathway studies for pharmacovigilance and toxicogenomics in childhood Acute Lymphoblastic Leukemia (ALL).
  • Pre-immunization of parental stem cell donors against leukaemia-specific mutations/SNPs for adoptive transfer.
  • Genetic epidemiology of cardiovascular diseases
  • Genetics of childhood obesity and other endocrinological disorders
  • Developmental genetics using Zebra fish as a model
  • Genetic epidemiology of cleft lip-palate.
  • Pre-implantation genetics
  • Molecular diagnostics and therapeutics in neuromuscular disorders
  • Genetic association and mutation studies in populations
  • Genetics of nephrotic syndrome in Singapore pediatric patients

 

 

Programme Highlights

 


Hematology and Oncology

  1. Collaboration with University of Malaya Medical Centre (Kuala Lumpur, KL); Subang Jaya Medical Centre (KL); KK Women’s and Children’s Hospital (KKH) and NUH:
    1. Malaysia-Singapore Acute Lymphoblastic Leukemia (ALL) 2008 study
    2. Malaysia-Singapore Acute Myeloid Leukemia (AML) 2006 study
  2. Collaboration with Roche Diagnostics – Microarray Innovative Leukemia Study – 2007/2008
  3. Collaboration with A/Prof Chia Kee Seng: Clinical Epidemiology and Population-Based Case-Control Studies in Cancer – Jul 2008

 


Molecular Diagnostics and Therapeutics in Neuromuscular Disorders

  1. Collaboration with Defence Medical Research Institute, Singapore General Hospital (SGH) and Faculty of Engineering, NUS: Development of high throughput diagnostic methods for muscle diseases such as Duchenne and Becker muscular dystrophy.
  2. Collaboration with KKH, SGH, Genome institute of Singapore, Institute of Medical Biology and National Cancer Centre: Genetic association and mutation studies in populations as basis for understanding gene structure and function.
  3. Member of the Pan-Asian SNP Initiative: Characterizing SNPs across 73 population groups to map human genetic diversity in Asia.

 


Cardiovascular Artery Disease (CAD):

Research on genes related to CAD, including genetic epidemiological studies of how genes influence plasma risk factors and clinical outcome, for delay and prevention of CAD

  


Minimal Change Nephrotic (MCN) Syndrome (CAD):

Investigation of molecular mechanism of podocyte effacement in MCNS in IL-13 over expressing rat model.

  

Research Achievements


Awards

Aug 2009: Prof Yap Hui Kim – Best Oral Presentation: 4th Scientific Meeting of Advanced Specialty Trainees in Nephrology, Singapore
Apr 2008: A/Prof Allen Yeoh – NMRC Clinician Scientist Investigator Award (Senior)
Mar 2008: RA/Prof Allen Yeoh – NUS Faculty Research Excellence Award
Nov 2007: Prof Yap Hui Kim – Young Investigator’s Gold Award: NHG Annual Scientific Congress (ASC) 2007, Singapore
Aug 2007: Prof Yap Hui Kim – Blue Ribbon Award: 14th Congress of the International Pediatric Nephrology Association

 

 
Commercialization

Licensing of the CAD Risk Assessment System to Novena Heart Centre (2009)

 

 
Patents

  1. Shallow Multi-well plastic chip for thermal multiplexing.
    SG Patent No.: 114901, Date Granted: 28/09/2007
  2. Determine the 3D structure for dust mite allergen that sensitized about 1 billion people worldwide.
  3. Immobilization unit and device for isolation of nucleic acid molecules.PCT Patent Application No.: PCT/SG2005/000374, Date Filed: 28/10/2005
  4. Bio-Conjugated Carbon Nanotubes Based Labels.U.S. Provisional Patent Application No.: 60/636,384, Date Filed: 26/8/2005

 

 

Key Representative Publications

 

  1. Zhao Y, Zhou S, Heng CK (2007). The Impact of Serum Amyloid A on Tissue Factor and Tissue Factor Pathway Inhibitor Expression and Activity in Endothelial Cells. Arterioscler Thromb Vascul Biol 27:1645-1650.
  2. He XL, Lu YJ, Saha N, Yang HY, Heng CK (2005) Acyl-CoA: Cholesterol Acyltransferase-2 Gene Polymorphisms and Their Association with Plasma Lipids and Coronary Artery Disease Risks. Hum Genet 118: 393–403.
  3. Chen HY, Kathirvel P, Yee WC, Lai PS (2009) Correction of dystrophia myotonica type 1 pre-mRNA transcripts by artificial trans-splicing. Gene Ther.16(2):211-7.
  4. Priya K, Jada SR, Quah BL, Quah TC, Lai PS (2009)High incidence of allelic loss at 16q12.2 region spanning RBL2/p130 gene in retinoblastoma. Cancer Biol Ther. 8(8):714-7.
  5. Kham SK, Soh CK, Aw DC, Yeoh AE. TPMT*26 (208F-->L), a novel mutation detected in a Chinese. Br J Clin Pharmacol. 2009 Jul;68(1):120-3.
  6. Yeoh AE, Lu Y, Chan JY, Chan YH, Ariffin H, Kham SK, Quah TC.Genetic susceptibility to childhood acute lymphoblastic leukemia shows protection in Malay boys: Results from the Malaysia-Singapore ALL Study Group. Leuk Res. 2009 Aug 1. [Epub ahead of print]
  7. Boyadjiev SA, Fromme JC, Ben J, Chong SS, Nauta C, Hur DJ, Zhang G, Hamamoto S, Schekman R, Ravazzola M, Orci L, Eyaid W. Cranio-lenticulo-sutural dysplasia is caused by a SEC23A mutation leading to abnormal ER-to-Golgi trafficking. Nature Genetics 38:1192-1197 (2006).
  8. Tan CY, Ho JFV, Chong YS, Loganath A, Chan YH, Ravichandran J, Lee CG, Chong SS. Paternal contribution of HLA-G*0106 significantly increases risk for pre-eclampsia in multigravid pregnancies. Molecular Human Reproduction 14:317-324 (2008).
  9. Hui Kim Yap, Kin Wai Lai, Chang Li Wei, Li Kiang Tan, Puay Hoon Tan, Gilbert Chiang, Caroline Lee, Stanley Jordan. Overexpression of Interleukin-13 induces minimal-change-like nephropathy in rats. Journal of the American Nephrology. April 2007 : 1476 – 1485
  10. Wei CL, Cheung W, Heng CK, Arty N, Chong SS, Lee BW, Puah KL, Yap HKInterleukin-13 genetic polymorphisms in Singapore Chinese children correlate with long-term outcome of minimal-change disease. Nephrology Dialysis Transplantation.20: 728-734. 2005

 


Member(s) of Programme


Programme Coordinators:

A/Prof Heng Chew Kiat


Members:

Dr Caroline G Lee
Dr Goh Li Meng, Denise
Dr Lai Poh San
Dr Lee Yung Seng
A/Prof Loke Kah Yin
Prof Low Poh Sim
A/Prof Quah Thuan Chong
A/Prof Quek Swee Chye
A/Prof Samuel S Chong
Dr Tay Kiat Hong, Stacey
Prof Yap Hui Kim
 
 

Associate Professor Heng Chew Kiat

Department of Paediatrics

The Children's Medical Institute
National University Hospital
5 Lower Kent Ridge Road
Singapore 119074
Tel     :  6772 5708
Fax    :  6774 2796
Email :  paehck@nus.edu.sg