Weiping HAN

Metabolic Medicine

PhD – Physiology, Cornell University, USA

LinkedIn: https://sg.linkedin.com/in/weipinghan

SUMMARY

Weiping Han is a Distinguished Principal Scientist as well as the Head of Laboratory of Metabolic Medicine (LMM) at the Agency for Science, Technology and Research Institute of Molecular and Cell Biology (A*STAR IMCB), . He was the founding director of Neurometabolism in Health & Disease at IMCB, and the Program Director of A*STAR’s Strategic Research Program Brain-Body Initiative (Neurometabolism). He is also Professor in the Department of Biochemistry and Member of the Neuroscience Program at National University of Singapore (NUS), and Professor in the Signature Research Program in Cardiovascular and Metabolic Disorders at Duke-NUS.

Weiping’s research investigates the critical role of metabolic states in maintaining cell survival and function, with a specific focus on the dysregulation and reprogramming of metabolic activities in the development of metabolic diseases and associated complications, especially liver cancer. His team has identified branched-chain amino acid, proline, and purine metabolism as key dysregulated pathways in human hepatocellular carcinoma and are actively pursuing pharmacological approaches to target these metabolic nodes for therapeutic intervention. These findings hold significant promise for developing novel treatments for this devastating disease, which currently has limited effective options. Besides his research efforts in cancer metabolism, he is also leading research programs and industry collaborations to develop next generation anti-obesity medications.

Weiping obtained his PhD in Physiology from Cornell University in 1996. He did his postdoctoral work at the University of Pittsburgh, and Howard Hughes Medical Institute (HHMI) and Center for Basic Neuroscience at the University of Texas (UT) Southwestern Medical Center in Dallas. In 2003, he was promoted to Research Assistant Professor in the Center for Basic Neuroscience at UT Southwestern Medical Center, where he studied molecular mechanisms of hormone secretion and signaling in diabetes development. In 2005, he was recruited by Sir George Radda to Singapore to set up a research program in metabolic medicine at the Singapore Bioimaging Consortium (SBIC), and was promoted to Research Director / Professor in 2013.

AWARDS & GRANTS

2025: A*STAR GAP Funding (Lead PI)
2024: Singapore Therapeutics Development Review (STDR) Pilot Grant (Lead PI)
2024: National Medical Research Council Open Fund-Individual Research Grant (NMRC OF-IRG (Lead PI)
2024: A*STAR GAP Funding (Lead PI)
2023: A*STAR GAP Funding (Lead PI)
2023: Singapore Therapeutics Development Review (STDR) Pre-Pilot Grant (Lead PI)
2023: A*STAR GAP Funding (Lead PI)
2021: A*STAR Strategic Research Programme (SRP) – Brain-Body Initiative
(Neurometabolism) (Lead PI)
2021: National Research Foundation (NRF) Competitive Research Programme (CRP) (Lead PI)

RESEARCH
Brain-Body Interaction
Our work focuses on understanding how the brain interacts with the organ systems to influence physical and mental health. Specifically, we investigate how metabolic regulators and metabolic states affect the brain and nervous system. Some of the genes being studied have been linked to neurological diseases like autism spectrum disorders and schizophrenia, and this work may offer targetable approaches in the treatment of these diseases.

Metabolic targets in liver cancer

We have discovered that changes in the metabolism of branched-chain amino acids (BCAAs) influence the development and progression of tumours. We identified that cancer cells specifically accumulate BCAAs to support its growth, by reducing the breakdown of BCAAs. By targeting BCAAs in tumours, our team is exploring new approaches to prevent and treat liver cancer.

Next-generation anti-obesity medications

While GLP-1 receptor agonists (GLP1-RA) demonstrate clinical efficacy, their use is often limited by significant gastrointestinal side effects. Long-term safety concerns have been raised due to persistent GLP-1 receptor activation in the brain and a potential link to depression and suicidal ideation. Furthermore, the loss of both fat and muscle mass associated with current therapies can negatively impact long-term health. We are working on developing next-generation anti-obesity drugs with prioritized targeting of fat loss and muscle preservation, while minimizing central actions.

Tackling type 2 diabetes

We have previously identified the critical regulator responsible for triggering the release of insulin. Type 2 diabetes, often attributed to obesity and a sedentary lifestyle, occurs when the pancreas is not making enough insulin (reduced insulin secretion) or cannot use insulin effectively (insulin resistance), leading to elevated levels of glucose in the blood. These findings could potentially provide therapeutic targets in insulin resistance and diabetes treatment.

PUBLICATIONS

Spatiotemporal control of subcellular O-GlcNAc signaling using Opto-OGT.
Ong Q, Lim R, Goh C, Liao Y, Chan SE, Lim C, Kam V, Yap J, Tseng T, Desrouleaux R, Wang LC, Ler SG, Lim SL, Kim S, Sobota RM, Bennett AM, Han W, Yang X (2024)
Nature Chemical Biology doi: 10.1038/s41589-024-01770-7
Amino acid is a major carbon source for hepatic lipogenesis.
Liao Y, Chen Q, Liu L, Sun J, Huang H, Bai X, Jin C, Li H, Sun F, Xiao X, Zhang Y, Li J, Han W, Fu S (2024)
Cell Metabolism 36(11):2437-2448.e8. doi: 10.1016/j.cmet.2024.10.001
Up-regulation of SLC7A11/xCT creates a vulnerability to selenocystine-induced cytotoxicity.
Tan SLW, Tan HM, Israeli E, Fatihah I, Ramachandran V, Ali SB, Goh SJA, Wee J, Tan AQL, Tam WL, Han W (2023)
Biochemical Journal 2023 Dec 20;480(24):2045-2058. doi: 10.1042/BCJ20230317
Nuanced contribution of gut microbiome in the early brain development of mice.
Yeo XY, Chae WR, Lee HU, Bae H-G, Pettersson S, Grandjean J, Han W, Jung S (2023)
Gut Microbes 2023 Nov 12. doi: 10.1080/19490976.2023.2283911
Schizophrenia-like behaviors arising from dysregulated proline metabolism are associated with altered neuronal morphology and function in mice with hippocampal PRODH deficiency.
Yao Y, Jin C, Liao Y, Huang X, Wei Z, Zhang Y, Li D, Su H, Han W*, Qin D*(2023)
Aging and Disease 15(4):1-17. September 25, 2023. DOI: 10.14336/AD.2023.0902
Functional activity of the caudate mediates the relation between early childhood microstructural variations and elevated metabolic syndrome scores.
Huang P, Tint MT, Lee M, Ngoh ZM, Gluckman P, Chong YS, Han W, Fu Y, Wee CL, Fortier MV, Ang KK, Lee YS, Yap F, Eriksson JG, Meaney MJ, Tan AP. (2023)
Neuroimage 278:120273. Doi: 10.1016/j.neuroimage.2023.120273

Genetic ablation of LAT1 inhibits growth of liver cancer cells and downregulates mTORC1 signaling.
Kim S-Y, Ong Q, Liao Y, Ding Z, Tan AQL, Lim LTR, Tan HM, Lim SL, Lee QY, Han W (2023)
International Journal of Molecular Science 24(11):9171 https://doi.org/10.3390/ijms24119171
Paired box 6 programs essential exocytotic genes in the regulation of glucose-stimulated insulin secretion and glucose homeostasis.
LSo WY, Liu WN, Teo AKK, Rutter GA, Han W (2021)
Sci Transl Med 2021 Jun 30;13(600):eabb1038. doi: 10.1126/scitranslmed.abb1038. PMID: 34193609
HOXC10 suppresses browning to maintain white adipocyte identity.
Tan HYA, Sim MFM, Tan SX, Ng Y, Gan SY, Li H, Neo SP, Gunaratne J, Xu F, Han W (2021)
Diabetes 2021 Aug;70(8):1654-1663. doi: 10.2337/db21-0114. Epub 2021 May 14. PMID:33990396; PMCID: PMC8385616
Metabolic pathway analyses identify proline biosynthesis pathway as a promoter of liver tumorigenesis.
Ding Z, Ericksen RE, Escande-Beillard N, Lee QY, Loh A, Denil S, Steckel M, Haegebarth A, Wai Ho TS, Chow P, Toh HC, Reversade B, Gruenewald S, Han W (2020)
J Hepatol 2020 Apr;72(4):725-735. doi:10.1016/j.jhep.2019.10.026. Epub 2019 Nov 11. PMID: 31726117

Weiping HAN

A*STAR celebrates International Women's Day