$25mil Translational and Clinical Research Grant over 5 years, by National Research Foundation.
Aims and Research Themes
Metabolic diseases in Asia have features which set them apart from what is seen in most Western countries and show ethnic differences not yet understood or explainable by genetics alone. The majority of diabetics in the world are Asian. Yet most research is done in the West despite the phenotype (physical and behavioural characteristics) of Asian diabetics being very different. For example, the relationship between body fat and cardiovascular risk in Indians and Chinese is quite different from that in Caucasians.
It is a matter of considerable societal, economic and strategic concern that Singapore has one of the highest incidences of diabetes in the developed world. What is equally gripping is that there are clear ethnic differences across the three major Singaporean ethnicities in terms of their propensity for metabolic disease.
Thus the focus of this programme is to address an emerging area of science that could profoundly influence the way metabolic disease, which has unique Asian features, is considered, prevented, and treated. Besides defining the developmental component of causation, this programme seeks interventions that will, in time, inform public health policies and guide clinical care of the rapidly growing populace with, or destined to be affected by, Type 2 Diabetes and its related diseases. Eventually, this could potentially lead to new therapeutic target identification and clinical applications.
Through these studies, the programme aims to:
- Understand factors in pregnancy and early childhood which cause epigenetic changes increasing the risks for metabolic disease in adulthood. This may lead to better ways of managing pregnancy and feeding newborns and infants (public health guidelines). Applications in the pharmaceutical and food industries are also envisaged.
- Identify epigenetic marks at birth that indicate increased risk for metabolic disease (biomarker and pathway discovery) allowing us to tailor interventions for individuals at risk as well as improve our understanding the mechanisms of these diseases.
- Discover effective prevention and early intervention strategies, which may be in the form of simple lifestyle and nutritional interventions or even prophylactic drugs.
- Develop cutting-edge expertise in developmental epigenetics, new capacity in translational and clinical research (capacity building), and gain novel insights in health promotion and clinical care of metabolic disease.
O2, CO2 & metabolic rate readings for SAMS participant under canopy hood in NUH
Molecular, genomic and epigenetic methodologies will be combined with physiological and clinical approaches in these projects:
1) Growing Up in Singapore Towards Healthy Outcomes(GUSTO) Study
2) Singapore Adult Metabolism Study (SAMS)
1) Growing Up in Singapore Towards Healthy Outcomes (GUSTO) Study
Mothers will be followed up from early pregnancy to document the pregnancy conditions and growth patterns of their babies and these will be correlated with the epigenetic changes detected in the placenta and umbilical cord of their babies at birth, along with their body composition.
The team will assess how these and genomic variation relate to subsequent growth and developmental patterns which lead to a predisposition to metabolic disease later on. Mothers for this study will be recruited mainly from KK Women's and Children's Hospital and from the National University Hospital.
Website: http://devos.sg/about/GUSTO.html and
GUSTO Launch, Speakers and Guests (29th Oct 2009)
L-R (back): Prof Mark Hanson, Prof Keith Godfrey, A/Prof Kenneth Kwek, Ms Cheryl McCaffery (Industry Development Group, A*STAR), Prof Michael Meany, Mr Jay Kaelash, Dr Allan Sheppard (SICS, A*STAR), Mr James Screen (British High Commission)
L-R (front): A/Prof Chong Yap Seng, Prof Saw Seang Mei, Lord Robert Winston, Sir Peter Gluckman
Mr Christopher Au, Dr Marielle Fortier, Dr Borys Shuter and Dr Jeevesh Kapur (off-camera) keep an eagle-eye on images coming in from the first GUSTO MRI in NUH.
2) Singapore Adult Metabolism Study (SAMS)
SAMS collaborators in SGH Life Centre.
L-R: Doris Fok, Kaelash Jayanadan, Gladys Woon, Dr Paul Deurenberg, Dr Scott Summers, Prof Klaas R Westerterp, A/Prof Lee Yung Seng, A/Prof Tai E Shyong, Dr Eric Khoo, A/Prof Melvin Leow, Dr Khoo Chin Meng, Eric Ho.
Studies in adults with diabetes and/or obesity will evaluate the relative importance of developmental and genetic pathways in contributing to individual risk and to the efficacy of weight loss interventions. These studies will also allow us to examine mechanisms underlying insulin resistance and ethnic differences in metabolic disease risk. These studies will be conducted in investigational medicine units in National University of Singapore and Singapore General Hospital.
- Broekman BF, Chan YH, Chong YS, Quek SC, Fung D, Low YL, Ooi YP, Gluckman PD, Meaney MJ, Wong TY, Saw SM. The influence of birth size on intelligence in healthy children. Pediatrics. 2009 Jun;123(6):e1011-6. [Learn more] [Free publication]
- Sabanayagam C, Shankar A, Chong YS, Wong TY, Saw SM. Breast‐feeding and overweight in Singapore school children. Pediatr Int. 2009 Oct;51(5):650‐6.
[Learn more] [Free publication]
- Chong YS, Kwek KY. Safer childbirth: avoiding medical interventions for non‐medical reasons. Lancet. 2010 Feb 6;375(9713):440-2. Epub 2010 Jan 11. [Learn more]
- Hornbeak DM, Dirani M, Sham WK, Li J, Young TL, Wong TY, Chong YS, Saw SM. Emerging trends in breastfeeding practices in Singaporean Chinese women: findings from a population‐based study. Ann Acad Med Singapore. 2010 Feb;39(2):88-94.
[Learn more] [Free full text] [PDF]
- Sham WK, Dirani M, Chong YS, Hornbeak DM, Gazzard G, Li J, Saw SM. Breastfeeding and association with refractive error in young Singapore Chinese children. Eye (Lond). 2010 May;24(5):875-80. Epub 2009 Sep 11. [Learn more] [Full article]
- Kok Hian Tan, Pratibha Agarwal, Siew Jong Hoon, Alex Sia, Kenneth Kwek, Integrated Perinatal Care and Beyond. Proceedings of Singapore Healthcare. 2010;19(2):124‐131. [PDF]
- Soh SE, Saw SM. Cohort studies: design and pitfalls. Am J Ophthalmol. 2010 Jul;150(1):3-5. [Learn more]
- Su LL, S K TC, Lim SL, Chen Y, Tan EA, Pai NN, Gong YH, Foo J, Rauff M, Chong YS. The influence of maternal ethnic group and diet on breast milk fatty acid composition. Ann Acad Med Singapore. 2010 Sep;39(9):675‐5. [Learn more] [PDF]
- Meaney MJ, Ferguson-Smith AC. Epigenetic regulation of the neural transcriptome: the meaning of the marks. Nat Neurosci. 2010 Nov;13(11):1313-8. [Learn more]
- Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC, McLean C, Rodford J, Slater‐Jefferies JL, Garratt E, Crozier SR, Emerald BS, Gale CR, Inskip HM, Cooper C, Hanson MA. Epigenetic gene promoter methylation at birth is associated with child's later adiposity. Diabetes. 2011 May;60(5):1528-34. Epub 2011 Apr 6.
[Learn more] [Free article] [PDF]
- Gluckman PD, Hanson M, Zimmet P, Forrester T. Losing the war against obesity: the need for a developmental perspective. Sci Transl Med. 2011 Jul 27;3(93):93cm19.
- Chng K, Chan L, Chong YS, Choo R, Meaney MJ, Holbrook JD, Gluckman PD. Correlation of Birth Weight and Maternal Weight Gain during Pregnancy in a Nonhuman Primate Model of Intrauterine Growth Restriction. J. Dev. Origins of Health and Disease Vol. 2, Suppl. 1, Sep 2011.
- Bright Starling Emerald, Keefe Chng, Shinya Masuda, Deborah M Sloboda, Mark H Vickers, Ravi Kambadur and Peter D Gluckman Gene expression profiling in the Cynomolgus macaque Macaca fascicularis shows variation within the normal birth range. BMC Genomics. 2011 Oct 16;12:509. [Learn more] [Full article]
- Anqi Qiu, Anne Rifkin-Graboi, Jidan Zhong, Desiree Yee-Ling Phua, Michael J. Meaney. Birth Weight and Gestation Influence Striatal Morphology and Motor Response in Normal Six-Year-Old Boys. Neuroimage. 2012 Jan 16;59(2):1065-70. Epub 2011 Sep 22.
- Das S, Zijdenbos AP, Harlap J, Vins D and Evans AC. LORIS: a web‐based data management system for multi‐center studies. Front Neuroinform. 2011;5:37. Epub 2012 Jan 20. [Learn more] [Free article] [PDF]
- Clarke IJ, Smith JT, Henry BA, Oldfield BJ, Stefanidis A, Millar RP, Sari IP, Chng K, Fabre‐Nys C, Caraty A, Ang BT, Chan L, Fraley GS. Gonadotropin inhibitory hormone (GnIH) provides a molecular switch between reproduction and feeding. Neuroendocrinology. 2012;95(4):305-16. Epub 2012 Jan 25. [Learn more]
- Shu E Soh, Samuel Shang Ming Lee, Sarah Wenli Hoon, Mae Yun Tan, Anne Goh, Bee Wah Lee, Lynette Pei‐Chi Shek, Oon Hoe Teoh, Kenneth Kwek, Seang Mei Saw, Keith Godfrey, Yap Seng Chong, Peter Gluckman, and Hugo PS van Bever. The methodology of the GUSTO cohort study: a novel approach in studying pediatric allergy. Asia Pac Allergy. 2012 Apr;2(2):144-8. Epub 2012 Apr 23. [Learn more] [Free full text] [PDF]
- Desiree Yee-Ling Phua, Anne Rifkin-Graboi, Saw Seang Mei, Michael J. Meaney, Anqi Qiu. Executive Functions of Six-Year-Old Boys with Normal Birth Weight and Gestational Age. PLoS One. 2012;7(4):e36502. Epub 2012 Apr 30. [Learn more] [Free full text] [PDF]
- Anqi Qiu, Anne Rifkin-Graboi, Ta Anh Tuan, Jidan Zhong, Michael J. Meaney. Inattention and hyperactivity predict alterations in specific neural circuits among normal 6-year-old boys. J Am Acad Child Adolesc Psychiatry. 2012 Jun;51(6):632-41. Epub 2012 Apr 24.
- Ling‐Jun Li, Carol Yim‐Lui Cheung, M.Kamran Ikram, Peter Gluckman, Michael J.Meaney, Yap‐Seng Chong, Kenneth Kwek, Tien‐Yin Wong and Seang‐Mei Saw. Blood Pressure and Retinal Microvascular Characteristics During Pregnancy : Growing Up in Singapore Towards Healthy Outcomes (GUSTO) Study . Hypertension. 2012 Jul;60(1):223-30. Epub 2012 May 21. [Free full text] [PDF]
- W Stünkel, H Pan, R Chew, E Tng, J H Tan, L Chen, R Joseph, C Cheong, Y S Lee, Y S Chong, S S Mei, M J Meaney, K Kwek, A M. Sheppard, P D Gluckman, GUSTO Study Group & J D Holbrook Transcriptome changes affecting hedgehog and cytokine signalling in the umbilical cord in late pregnancy: implications for disease risk. PLoS One. 2012;7(7):e39744. Epub 2012 Jul 10. [Learn more] [Free article] [PDF]
- Lynette P. Shek, Mary Foong-Fong Chong, Jia Yi Lim, Shu-E Soh, and Yap-Seng Chong. Role of Dietary Long-Chain Polyunsaturated Fatty Acids in Infant Allergies and Respiratory Diseases. Clin Dev Immunol. 2012;2012:730568. Epub 2012 Aug 28.
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- Ling‐Jun Li, M. Kamran Ikram, Carol Yim‐Lui Cheung, Yung‐Seng Lee, Lin‐Jun Lee, Peter Gluckman, Keith M Godfrey, Yap‐Seng Chong, Kenneth Kwek, Tien‐Yin Wong, Seang‐Mei Saw. Effect of maternal body mass index on the retinal microvasculature in pregnancy. Obstet Gynecol. 2012 Sep;120(3):627-35. [Learn more]
- Pan H, Chen L, Dogra S, Teh AL, Tan JH, Lim YI, Lim YC, Jin S, Lee YK, Ng PY, Ong ML, Barton S, Chong YS, Meaney MJ, Gluckman PD, Stunkel W, Ding C, Holbrook JD. Measuring the methylome in clinical samples: improved processing of the Infinium Human Methylation450 BeadChip Array. Epigenetics. 2012 Oct;7(10):1173-87. Epub 2012 Sep 10. [Learn more]
- Bai J, Abdul-Rahman MF, Rifkin-Graboi A, Chong YS, Kwek K, Saw SM, Godfrey KM, Gluckman PD, Fortier MV, Meaney MJ, Qiu A. Population differences in brain morphology and microstructure among Chinese, Malay, and Indian neonates. PLoS One. 2012;7(10):e47816. Epub 2012 Oct 24. [Learn more] [Full article] [PDF]
- Lim AL, Ng S, Leow SC, Choo R, Ito M, Chan YH, Goh SK, Tng E, Kwek K, Chong YS, Gluckman PD, Ferguson-Smith AC. Epigenetic state and expression of imprinted genes in umbilical cord correlates with growth parameters in human pregnancy. J Med Genet. 2012 Nov;49(11):689-97. Epub 2012 Oct 5. [Learn more]
- Qiu A, Fortier MV, Bai J, Zhang X, Chong YS, Kwek K, Saw SM, Godfrey KM, Gluckman PD, Meaney MJ. Morphology and microstructure of subcortical structures at birth: A large-scale Asian neonatal neuroimaging study. Neuroimage. 2013 Jan 15;65:315-23. Epub 2012 Sep 18. [Learn more]
- Li LJ, Ikram MK, Broekman BF, Cheung CY, Chen H, Gooley JJ, Soh SE, Gluckman P, Kwek K, Chong YS, Meaney M, Wong TY & Saw SM. Antenatal Mental Health and Retinal Vascular Caliber in Pregnant Women. Trans Vis Sci Tech. 20 Feb 2013;2(2):2.
[Full text] [PDF]
- Jidan Zhong, Anne Rifkin-Graboi, Anh Tuan Ta, Kar Lai Yap, Kai-Hsiang Chuang, Michael J. Meaney, Anqi Qiu. Functional Networks in Parallel with Cortical Development Associate with Executive Functions in Children. Cereb Cortex. 2013 Feb 28.
- Aris IM, Soh SE, Tint MT, Liang S, Chinnadurai A, Saw SM, Kwek K, Godfrey KM, Gluckman PD, Chong YS, Yap FK & Lee YS. Body fat in Singaporean infants: development of body fat prediction equations in Asian newborns. Eur J Clin Nutr. 2013 Apr 3. [Learn more]
- Lee Y, Chong MF, Liu JC, Libedinsky C, Gooley JJ, Chen S, Wu T, Tan V, Zhou M, Meaney MJ, Lee YS, Chee MW. Dietary disinhibition modulates neural valuation of food in the fed and fasted states. Am J Clin Nutr. 2013 May;97(5):919-25. Epub 2013 Apr 3. [Learn more]
- Chen LW, Low YL, Fok D, Han WM, Chong YS, Gluckman P, Godfrey K, Kwek K, Saw SM, Soh SE, Tan KH, Chong MF, van Dam RM. Dietary changes during pregnancy and the postpartum period in Singaporean Chinese, Malay and Indian women: the GUSTO birth cohort study. Public Health Nutr. 2013 Jun 28:1-9. [Learn more]
- Ratnarajah N, Rifkin-Graboi A, Fortier MV, Chong YS, Kwek K, Saw SM, Godfrey KM, Gluckman PD, Meaney MJ & Qiu A. Structural connectivity asymmetry in the neonatal brain. Neuroimage. 2013 Jul 15;75:187-94. Epub 2013 Mar 14. [Learn more]
- Lim LS, Chong GH, Tan PT, Chong YS, Kwek K, Gluckman PD, Fortier MV, Saw SM, Qiu A. Distribution and determinants of eye size and shape in newborn children: a magnetic resonance imaging analysis. Invest Ophthalmol Vis Sci. 2013 Jul 16;54(7):4791-7.
- Soh SE, Tint MT, Gluckman PD, Godfrey KM, Rifkin-Graboi A, Chan YH, Stünkel W, Holbrook JD, Kwek K, Chong YS, Saw SM; the GUSTO Study Group. Cohort Profile: Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study. Int J Epidemiol. 2013 Aug 2. [Learn more]
- Rifkin-Graboi A, Bai J, Chen H, Hameed WB, Sim LW, Tint MT, Leutscher-Broekman B, Chong YS, Gluckman PD, Fortier MV, Meaney MJ, Qiu A. Prenatal Maternal Depression Associates with Microstructure of Right Amygdala in Neonates at Birth. Biol Psychiatry. 2013 Aug 19. [Epub ahead of print] [Learn more]
Last updated 4 September 2013