Prof Lee Yung Seng

Appointment(s)

Group Chief, Paediatrics, National University Health System

Co-Director, National University Centre for Women and Children, National University Health System

Head, Khoo Teck Puat – National University Children’s Medical Institute, National University Hospital

Head, Department of Paediatrics & Senior Consultant, Division of Paediatric Endocrinology, Khoo Teck Puat – National University Children’s Medical Institute, National University Hospital

Head & Professor, Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore

Deputy Director, Translational Research Programme (Synthetic Biology), Yong Loo Lin School of Medicine, National University of Singapore

Degree(s)

MBBS (S’pore), MMed (Paeds) (S’pore), MRCP (UK), FRCPCH (UK), FAMS (Paeds) S’pore), PhD

Biography

Prof Lee is a practicing senior consultant paediatrician of the paediatric endocrinology service at the Khoo Teck Puat-National University Children’s Medical Institute, National University Hospital, and also a tenured professor of the Yong Long Lin School of Medicine, National University of Singapore. He was the president (2020-2022) of the Asia Pacific Paediatric Endocrine Society (APPES), and the president (2021-2023) of the College of Paediatrics and Child Health, Academy of Medicine, Singapore.

His clinical and research interest is in obesity, diabetes, and growth. His research is focused on obesity, insulin resistance, and mediators of obesity related morbidities. His research approach to elucidate the biological susceptibility to human obesity and related morbidities is three pronged, by studying the 1) genetics, 2) In-utero and early life developmental factors (developmental origins of health and disease), and 3) role of gut microbiome. He has also research interest in engineering probiotics to confer health benefits and disease treatment. His other clinical research also encompasses various paediatric endocrine disorders. He has more than 250 publications in local and international journals (as of 2024).

In the recent years, Prof Lee has focused his efforts on the developing programmes and strategies to advance child and maternal health, promoting healthy living for families, and improving health equity through his leadership role at the National University Centre for Women and Children.

Research Areas/Research Interest

1. Research Programmes
a) *Genetics of obesity (2001- to date)
My primary interest is in single gene mutations which cause human obesity, as well as susceptibility genes which predispose to obesity. I have focused on this field of research since 2001, and have managed to recruit nearly 300 severely obese children and created a biodatabank; we have found several children with gene defects (MC3R and MC4R genes) which disrupt the weight regulation mechanism. I had the privilege of spending two years of research training (Sep 03 Aug 05) with the Genetics of Obesity Study (GOOS) in Cambridge to study POMC gene mutations which predispose to human obesity in a UK obese cohort (Cell Metab 2006).
I have also collected anthropometric, clinical, and biochemical data of the local obese cohort to study obesity-related complications such as non-alcoholic fatty liver disease, hypertension, dyslipidemia, insulin resistance and glucose intolerance. We are currently working on genes which may predispose these individuals to these complications.
We have presented these findings in various international and local conferences, and the work is recognised with various local and regional awards. We published the first report of human MC3R mutation associated with human obesity (J Clin Endocrinol Metab 2002), and a second paper on other MC3R mutations (Diabetes 2007) (both Tier 1). We have published papers on MC4R mutations and non-alcoholic fatty liver disease in childhood obesity to Tier 2 and 3 journals. I have completed by PhD defence in Jan 09 successfully based on this work.
Importantly, my long term research aim is to build up a bio-databank of severely obese children. Thus I wish to continue to recruit severely obese children, and plan to seek collaborators from other clinical units in Singapore, and in the Asia-Pacific region. The on-going study will ultimately serve as a springboard for further research to determine other candidate genes involved in common obesity, including linkage analysis to determine the susceptibility loci unique to our population and region, when sufficient samples have been collected.
b) Use of Pamidronate and Growth Hormone in Osteogenesis Imperfecta (2000 – 2003) (investigator-initated).
Examine the effects of combined pamidronate and growth hormone therapy on fracture risk, bone density and bone turnover rate in children with osteogenesis imperfecta. Study is approved by NUH ethics committee in November 2000, and recruitment has started since February 2001. The study is closed and a conference paper has been published.
c) Use of Pamidronate in children with osteogenesis imperfecta (1998 to date)
Initiated in 1998, the use of pamidronate in osteogenesis imperfecta was still a relatively novel therapy then. Our regimen comprised of pamidronate infusion over a few hours once in two months has resulted in significant improvement in bone mineral density, reduced bone turnover, and reduced fracture rates in six children with osteogenesis imperfecta (European Journal of Paediatrics 2001). The paper was presented in the NUH-Faculty of Medicine,NUS scientific meeting 2000 and Singapore-Malaysia Congress of Medicine / Combined Hospitals Medical & Dental Scientific Meeting Aug 2000. We are still continuing our surveillance for long term effects especially on growth and bone density.
We also examined the effects of combined pamidronate and growth hormone therapy on fracture risk, bone density and bone turnover rate in children with osteogenesis imperfecta (investigator-initated, 2000). The study is closed and two conference papers have been published.
d) Normative values of bone mineral density and body fat mass in local children (May 2001 2004)
This NMRC-NHG sponsored study established the normal reference range of areal and volumetric body mineral density of healthy Singapore children using Dual Energy X-ray Absorptiometry (DEXA) technique as well as bone strength using the calaneal Broadband Ultrasound Attenuation (BUA) method, which will be invaluable in the management of children with chronic illnesses which can cause osteoporosis. Using these normative data for comparison, our team has recently embarked on a project to study the changes in bone mineral density and bone strength in children with asthma on inhaled steroids, chronic/end-stage renal failure, and steroid dependent nephrotic syndrome.
e) Co-investigator for Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) (17 April 2000 to 2003).
This was a post-marketing research programme to evaluate the long-term safety and efficacy of a growth hormone Humatrope based on data collected in an observational setting. The company-initiated study also includes numerous sub-studies to analyse gene defects as causes of short stature, growth prediction model to optimise growth hormone therapy, growth data of patients with SHOX deficiency, and treatment and outcome history of patients treated for neoplasia. This was a multicenter global programme, and our unit was the only study site in Singapore.
f) International Trial on efficacy and safety of Avandia in Children and Adolescents Dec 2001 Nov 2002
This was a double blind randomised controlled trial which examines the efficacy of metformin and a new oral agent for the management of childhood and adolescent type 2 diabetes.
g) Expression studies of a novel 111 bp duplication in exon 1 of the CYP21 gene in the pathogenicity of simple virilising congenital adrenal hyperplasia (Academic research fund for two years from November 1999. $25,000)
The commonest form of congenital adrenal hyperplasia is 21-hydroxylase deficiency. For the past 2 years, we have analysed the genotypes of individuals with 21-hydroxylase deficiency. In the process of screening, we have discovered two patients with a potentially novel mutation. This potential mutation involves a duplication of 111 base pairs in exon 1, at nucleotide position 176. Our aim is to confirm the hypothesis that the exon 1 duplication of 111bp encodes mutant 21-hydroxylase enzyme responsible for the virilisation in 21-hydroxylase deficiency.
h) Prevalence of autoantibodies in children with type 1 diabetes mellitus
A review of 41 children with type 1 diabetes has established that only 41.6% of our study sample is positive for islet-cell antibodies and/or anti-GAD antibodies, which is similar to other Asian studies, but much less than those reported in Caucasian populations. This implied that there is a possible difference in the pathogenesis of type 1 diabetes between Asian and Caucasian population. The paper was published in an international journal (journal of pediatric endocrinology and metabolism).
i) Detection of salivary anti-GAD and ICA antibodies in children with type 1 diabetes.
We are currently collaborating with Mr Alan Todd (MSc student), Dr Ng Wai Yoong and A/Prof Thai Ah Chuan (Dept of Medicine) to develop the technique of detection of salivary anti-GAD and ICA antibodies. This technique will enable mass screening for children in pre-diabetic state in populations whose type 1 diabetics have a high prevalence of diabetes-associated antibodies.
j) Genotype-phenotype correlation in the 21-hydroxylase deficient form of congenital adrenal hyperplasia (1998-1999), and Expression studies of a novel 111 bp duplication in exon 1 of the CYP21 gene in the pathogenicity of simple virilising congenital adrenal hyperplasia (1999-2001)
The genotypes of 33 children with 21-hydroxylase deficiency were examined and correlated with their phenotype. It was found that the severity of the phenotype can be predicted in 91% of the cases based on the genotype, which has important implications in the management of the patients. Novel mutations were found and expression studies have supported a pathogenetic role. The paper is selected for oral presentation at the Inaugural Scientific Meeting of Asia Pacific Paediatric Endocrine Society in July 99, and three novel mutations was reported in the 5th NUH-NUS Faculty of Medicine Annual Scientific Meeting, 29-30 June2001, and was awarded the Best Clinical Science Poster Award. The data has also been published in an international journal (Hormone Research).
k) Prevalence of invasive Haemophilus Influenzae type b infections in Singapore children (1998-1999)
A 6-year (1990 to 1995) hospital-based retrospective study was carried out to study the pattern of invasive Haemophilus influenzae type b (Hib) disease in children admitted to NUH. We concluded that invasive Hib infections are relatively uncommon in our community. This justifies the need for a cost effective study before a universal vaccination programme in our infants is implemented.

Selected Publications

Timing of introduction of complementary foods, breastfeeding, and child cardiometabolic risk: a prospective multiethnic Asian cohort study

Ong YY, Pang WW, Michael N, Aris IM, Sadananthan SA, Tint M-T, Choo JTL, Ling LH, Karnani N, Velan SS, Fortier MV, Tan KH, Gluckman PD, Yap F, Chong Y-S, Godfrey KM, Chan S-Y, Eriksson JG, Chong MF-F, Wlodek ME, Lee YS

Newborn body composition and child cardiovascular risk markers: a prospective multi-ethnic Asian cohort study

Ong YY, Tint M-T, Aris IM, Yuan WL, Chen L-W, Fortier M, Choo J, Ling LH, Shek L, Tan KH, Gluckman PD, Yap F, Chong Y-S, Godfrey KM, Chong MF-F, Chan S-Y, Eriksson JG, Wlodek ME, Rolfe EDL, Ong KK, Michael N, Lee YS

Implication of gut microbiota in the association between infant antibiotic exposure and childhood obesity and adiposity accumulation

Chen L-W, Xu J, Soh SE, Aris IM, Tint M-T, Gluckman PD, Tan KH, Shek LP-C, Chong Y-S, Yap F, Godfrey KM, Gilbert JA, Karnani N, Lee YS

Modifiable risk factors in the first 1000 days for subsequent risk of childhood overweight in an Asian cohort: significance of parental overweight status

Aris IM, Bernard JY, Chen L-W, Tint MT, Pang WW, Soh SE, Saw S-M, Shek LP-C, Godfrey KM, Gluckman PD, Chong Y-S, Yap F, Kramer MS, Lee YS

Infant body mass index peak and early childhood cardio-metabolic risk markers in a multi-ethnic Asian birth cohort

Aris IM, Bernard JY, Chen L-W, Tint MT, Pang WW, Lim WY, Soh SE, Saw S-M, Godfrey KM, Gluckman PD, Chong Y-S, Yap F, Kramer MS, Lee YS

Associations of gestational glycemia and prepregnancy adiposity with offspring growth and adiposity in an Asian population

Aris IM, Soh SE, Tint MT, Saw SM, Rajadurai VS, Godfrey KM, Gluckman PD, Yap F, Chong YS, Lee YS

Effect of Maternal Glycemia on Neonatal Adiposity in a Multiethnic Asian Birth Cohort

Aris IM, Soh SE, Tint MT, Liang S, Chinnadurai A, Saw SM, Rajadurai VS, Kwek K, Meaney MJ, Godfrey KM, Gluckman PD, Yap FKP, Chong YS, Lee YS

The role of melanocortin 3 receptor gene in childhood obesity

Lee YS, Poh LKS, Kek BLK, Loke KY

A POMC variant implicates β-melanocyte-stimulating hormone in the control of human energy balance

Lee YS, Challis BG, Thompson DA, Yeo GSH, Keogh JM, Madonna ME, Wraight V, Sims M, Vatin V, Meyre D, Shield J, Burren C, Ibrahim Z, Cheetham T, Swift P, Blackwood A, Hung CCC, Wareham NJ, Froguel P, Millhauser GL, O'Rahilly S, Farooqi IS

A novel melanocortin 3 receptor gene (MC3R) mutation associated with severe obesity

Lee YS, Poh LKS, Loke KY