Affiliations

Assistant Professor, Department of Biochemistry and Department of Medicine, Yong Loo Lin School of Medicine, NUS
Principal Investigator, Institute of Molecular and Cell Biology, A*STAR

Education

Professional Experience

Research Projects

Diabetes is a debilitating chronic disease spiralling out of control, affecting more than 400 million people in the world. People with diabetes commonly develop severe complications such as blindness, cardiovascular diseases, kidney failures and lower limb amputations, leading to an astronomical healthcare burden. Despite intensive research, mechanisms underlying human pancreatic β cell failure during the development of diabetes and its eventual dysfunction remain to be elucidated. Species-specific differences in pancreas development, islet architecture and distribution pattern of islet cells necessitate a human model for diabetes research.

The Teo Lab seeks to leverage on human cell models such human pluripotent stem cell (hPSC)-derived cells, human islets and human β cells to study diabetes disease mechanisms, develop therapeutics for diabetes and use them as a cell source for cell therapy in diabetes. The three main thrusts of the lab are:

1) MODELLING AND STUDYING HUMAN DIABETES DISEASE MECHANISMS

hPSCs that comprise of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) derived from patients with monogenic, gestational, type 1 or type 2 diabetes patients will be differentiated into human pancreatic cells or cell types affected in diabetic complications to dissect the pathology of diabetes and its complications. This effort will also contribute directly to the understanding of human potential and development.

The process of differentiating hPSCs into pancreatic β-like cells will be used to study human β cell development, maturation and function. This will identify critical steps, key pathways and mechanisms which guide human β cell development and maturation.

Differentiating hiPSCs that harbour diabetes risk alleles will pinpoint mechanisms of β cell demise at the earliest stage(s) and functionalise the gene variants associated with diabetes. This is otherwise not possible given that clinical manifestation of overt diabetes in humans takes decades to occur and patient material is inaccessible.

Differentiating hiPSCs from diabetic patients with and without complications, such as diabetic nephropathy, will elucidate genetic and epigenetic perturbations which occur in cells/tissues/organs constantly exposed to hyperglycaemia.

2) DEVELOPING NEW THERAPEUTICS TO IMPROVE PANCREATIC Β CELL FUNCTION

Patient-specific hiPSCs with clinical deficiencies in insulin secretion, such as that of MODY1 and MODY3, will be used to identify new targets and pathways relating to insulin secretion mechanisms.

Novel biological and natural products will also be tested on human islets and human β cells with the goal of identifying new molecules or signalling pathways that can regulate β cell insulin secretion capacity.

3) DEVELOPING STEM CELL-BASED THERAPIES FOR THE TREATMENT OF DIABETES

Human stem cells are highly renewable and non-xenogenic. Therefore, they can be appropriately positioned for cell therapy in diabetes patients. Current Good Manufacturing Practice (cGMP) hPSC-derived β cells can potentially be used for islet cell replacement therapy in diabetes patients. Multipotent mesenchymal stromal cells (MSCs) can also be used to confer beneficial immunomodulatory properties upon transplanted human islets or β cells to improve the long-term success of cell replacement therapy. Last but not least, bioengineering efforts including the development of encapsulation devices or the use of scaffolds will complement these stem cell-based development efforts. Together, it is envisioned that the production of sufficient mature and functional human β cells from hPSCs for cell replacement therapy will achieve physiological control of blood glucose levels, to provide a better life for diabetes patients.

Selected Publications

1. Lau, H.H.#, Krentz, A.J.N.#, Abaitua, F., Perez-Alcantara, M., Chan, J.W., Ajeian, J., Ghosh, S., Lee, Y., Yang, J., Thaman, S., Champon, B., Sun, H., Jha, A., Hoon, S., Tan, N.S., Gardner, D., Kao, S.L., Tai, E.S., Gloyn, L.A.*, and Teo, K.K.A.* (2023). PAX4 loss of function increases diabetes risk by altering human pancreatic endocrine cell development. Nat Comms 14, 6119. #First authors *Corresponding authors
2. Chan, J.W.#, Neo, W.Y.C.#, Ghosh, S., Choi, H.W., Lim, S.C., Tai, E.S., and Teo, K.K.A. (2023). HNF1A binds and regulates the expression of SLC51B to facilitate the uptake of estrone sulfate in human renal proximal tubule epithelial cells. Cell Death Disease 14(5), 302. #First authors
3. Tan, W.X., Sim, X.L., Khoo, C.M., and Teo, K.K.A. (2023). Prioritization of type 2 diabetes-associated genes for functional studies. Nat Rev Endocrinol. 19, 477-486.
4. Lim, Y.X.L., Ding, S.L.S., Muthukumaran, P., Teoh, S.H., Koh, Y.X., and Teo, K.K.A. (2023). Tissue engineering of decellularized pancreas scaffolds for regenerative medicine in diabetes. Acta Biomaterialia 157, 49-66.
5. Lau, H.H.#, Gan, S.U.#, Lickert, H., Shapiro, J.A., Lee, K.O., and Teo, K.K.A. (2021). Charting the next century of insulin replacement with cell and gene therapies. Med 2, 1138-1162. #First authors (Journal Cover Image)
6. Soetedjo, A.A.P.#, Lee, J.M.#, Lau, H.H.#, Goh, G.L., An, J., Koh, Y.X., Yeong, W.Y., and Teo, K.K.A. (2021). Tissue engineering and 3D printing of bioartificial pancreas for diabetes. Trends Endo Metab 32(8), 609-622. #First authors
7. Nguyen, L., Lim, Y.X.L., Ding, S.L.S., Amirruddin, N.S., Hoon, S., Chan, S.-Y., and Teo, K.K.A. (2021). Metformin perturbs pancreatic differentiation from human embryonic stem cells. Diabetes 70(8), 1689-1702.
8. Amirruddin, N.S., Tan, W.X., Tan, Y.S., Gardner, D., Bee, Y.M., Verma, C.S., Hoon, S., Lee, K.O., and Teo, K.K.A. (2021). Progressive endoplasmic reticulum stress over time due to human insulin gene mutation contributes to pancreatic beta cell dysfunction. Diabetologia 64(11), 2534-2549.
9. Low, S.J.B., Lim, C.S., Tan, Y.S., Ding, S.L.S., Ng, H.J.N., Krishnan, V.G., Ang, S.F., Neo, W.Y.C., Verma, C.S., Hoon, S., Lim, S.C., Tai, E.S., and Teo, K.K.A. (2021). Decreased GLUT2 and glucose uptake contribute to insulin secretion defects in MODY3/HNF1A hiPSC-derived mutant β cells. Nat Comms 12, 3133.
10. Loo, S.W.L., Soetedjo, A.A.P., Lau, H.H., Ng, H.J.N., Ghosh, S., Nguyen, L., Krishnan, V.G., Choi, H., Roca, X., Hoon, S., and Teo, K.K.A. (2020). BCL-xL/BCL2L1 is a critical anti-apoptotic protein that promotes the survival of differentiating pancreatic cells from human pluripotent stem cells. Cell Death Disease 11, 378.