Adrian Kee Keong TEO 
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  Adrian Kee Keong TEO  
  Lab Location: #6-07

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  Key Publications  

Loo, S.W.L., Lau, H.H., Jasmen, J., Lim, C.S., and Teo, K.K.A. (2017).
An arduous journey from human pluripotent stem cells to functional pancreatic β-cells.
Diabetes, Obesity and Metabolism, in press.

Teo, K.K.A.*, Lau, H.H., Valdez, I.A., Dirice, E., Tjora, E., Raeder, H., and Kulkarni, R.N.* (2016).
Early developmental perturbations in a human stem cell model of MODY5/HNF1B pancreatic hypoplasia.
Stem Cell Reports 6, 357 367.
*Corresponding authors

Santosa, M., Low S.J.B., Pek M.Q.N., and Teo, K.K.A. (2016).
Knowledge gaps in rodent pancreas biology: taking human pluripotent stem cell-derived pancreatic beta cells into our own hands.
Front. Endocrinol. 6,194.

Teo, K.K.A.*, Gupta, M.K., Doria, A., and Kulkarni, R.N.* (2015).
Dissecting diabetes/metabolic disease mechanisms using pluripotent stem cells and genome editing tools.
Mol Metab 4, 593-604.
*Corresponding authors

Teo, K.K.A., Tsuneyoshi, N., Hoon, S., Tan, E.-K., Stanton, L.W., Wright, C.V., and Dunn, N.R. (2015).
PDX1 binds and represses hepatic genes to ensure robust pancreatic commitment in differentiating human embryonic stem cells.
Stem Cell Reports 4, 578-590.

Valdez, I.A.#, Teo, K.K.A.#*, and Kulkarni, R.N.* (2015).
Cellular stress drives pancreatic plasticity.  
Sci. Transl. Med.
 7, 273ps2.
#First authors
*Corresponding authors

Teo, K.K.A.*, Valdez, I.A., Dirice, E., and Kulkarni, R.N.* (2014).
Comparable generation of Activin-induced definitive endoderm via additive Wnt or BMP signalling in absence of serum.
Stem Cell Reports 3, 5-14.
*Corresponding authors

Teo, K.K.A., Wagers, A.J., and Kulkarni, R.N. (2013).
New opportunities: harnessing induced pluripotency for discovery in diabetes and metabolism.
Cell Metabolism 18, 775-791.

Teo, K.K.A., Windmueller, R., Johansson, B.B., Dirice, E., Njolstad, P.R., Tjora, E., Raeder, H., and Kulkarni, R.N. (2013).
Derivation of human induced pluripotent stem cells from patients with maturity onset diabetes of the young.
J Biol Chem 288, 5353-5356.

Teo, K.K.A.*, Ali, Y.*, Wong, K.Y., Chipperfield, H., Sadasivam, A., Poobalan, Y., Tan, E.-K., Wang, S.-T., Abraham, S., Tsuneyoshi, N., Stanton, L.W., and Dunn, N.R. (2012).
Activin and BMP4 synergistically promote formation of definitive endoderm in human embryonic stem cells.
Stem Cells 30, 631-642.
*Equal contribution

Teo, K.K.A., Arnold, S.J., Trotter, M.W.B., Brown, S., Ang, L.T., Chng, Z., Robertson, E.J., Dunn, N.R., and Vallier, L. (2011). Pluripotency factors regulate definitive endoderm specification through Eomesodermin.
Genes Dev 25, 238-250.

Teo, K.K.A., and Vallier, L. (2010).
Emerging use of stem cells in regenerative medicine.
Biochem J 428, 11-23.



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  Adrian Kee Keong TEO

Adrian obtained his B.Sc. (1st Class Honours) from the National University of Singapore in February 2007. He then started to work on human embryonic stem cells (hESCs) with Ray Dunn, Ph.D., and Alan Colman, Ph.D., at ES Cell International Pte. Ltd., before joining the Institute of Medical Biology (IMB), A*STAR, Singapore, for an internship as a Research Officer in the laboratory of Ray Dunn, Ph.D.. In April 2008, he joined the laboratory of Ludovic Vallier, Ph.D., at the University of Cambridge to pursue his Ph.D. under the A*STAR Graduate Scholarship (Overseas). Concurrently, he was also an Honorary Cambridge Commonwealth Trust Scholar. His thesis described how pluripotency factors regulate endoderm specification via key regulator EOMESODERMIN. He completed his Ph.D. in July 2010 and joined the laboratory of Ray Dunn, Ph.D., at IMB as a postdoctoral fellow before heading to the laboratory of Rohit Kulkarni, M.D. Ph.D., at Joslin Diabetes Center, Harvard Medical School in September 2011. During his fellowship at Joslin, he obtained two Harvard Stem Cell Institute seed grants and a Juvenile Diabetes Research Foundation (JDRF) fellowship to pursue his research interests in using human pluripotent stem cells (hPSCs) for in vitro disease modelling of diabetes. Adrian is currently a junior investigator at the Institute of Molecular and Cell Biology (IMCB), A*STAR, an Adjunct Assistant Professor at the School of Biological Sciences, Nanyang Technological University, Singapore and an Adjunct Assistant Professor at the Department of Biochemistry, NUS Medicine, Singapore. He is a member of the Oxford and Cambridge Society of Singapore, the International Society for Stem Cell Research (ISSCR) and Stem Cell Society Singapore.

  Stem Cells and Diabetes

Diabetes is a debilitating chronic disease spiralling out of control, affecting more than 380 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, early mechanisms underlying human pancreatic β cell failure during the development of diabetes remain unclear. 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 pluripotent stem cells (hPSCs) and their directed differentiation into pancreatic cells and cell types affected in diabetic complications to dissect the pathology of diabetes and its complications (Figure 1). The three main thrusts of the lab are:

1)  Modelling and studying human pancreas development in vitro

hPSCs will be differentiated into human pancreatic cells to study the development and formation of functionally mature β cells. This is aimed at identifying critical steps, key pathways and mechanisms which guide human β cell development and maturation. It is hoped that one would be able to produce sufficient mature functional human β cells for cell replacement therapy to achieve physiological control of blood glucose levels.

2)  Studying mechanisms by which genes and gene variants cause diabetes

hiPSCs derived from patients with maturity onset diabetes of the young (MODY), a monogenic form of diabetes, will be used to study human β cell development, maturation and function. hiPSCs derived from diabetic patients with a risk allele that could potentially confer diabetes susceptibility will be differentiated into pancreatic cells to functionalise gene variants associated with diabetes. The tracking of early diabetes progression in vitro seeks to pinpoint mechanisms of β cell demise at the earliest stage(s). This is otherwise not possible given that clinical manifestation of overt diabetes in humans takes decades to occur and patient material is inaccessible.

3)  Studying mechanisms underlying diabetic complications

hiPSCs derived from diabetic patients with and without complications, such as diabetic nephropathy, will be differentiated into kidney cells to elucidate genetic and epigenetic perturbations which occur in cells/tissues/organs constantly exposed to hyperglycemia.

Figure Legend:
Differentiation of hiPSCs derived from diabetic patients into various cell types for in vitro disease modelling of diabetes and its complications. (Teo et al., Cell Metab, 2013)