Adrian Kee Keong TEO

Stem Cells and Diabetes


Adrian Kee Keong TEO
Lab Location: #6-07   Email:   Tel: 65869641

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 Principal Investigator at the Institute of Molecular and Cell Biology (IMCB), A*STAR, an Assistant Professor at the Department of Biochemistry and Department of Medicine, NUS Medicine, Singapore and an Adjunct Assistant Professor at the School of Biological Sciences, Nanyang Technological University, Singapore. He is a member of the Oxford and Cambridge Society of Singapore, the International Society for Stem Cell Research (ISSCR) and an EXCO member of the 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)


Department: Adrian Kee Keong TEO

Name: Thi Ha Linh NGUYEN

Designation: SINGA Student


Name: Nur Shabrina Binte AMIRRUDDIN

Designation: PhD Student


Name: Adrian Kee Keong TEO

Designation: Principal Investigator


Name: Natasha Hui Jin NG

Designation: Research Fellow


Name: Andreas Alvin SOETEDJO

Designation: Research Officer


Name: Wen Ying, Claire NEO

Designation: PhD Student


Name: Shirley Suet Lee DING

Designation: Research Officer


Name: Wei Xuan TAN

Designation: PhD Student


Name: Chek Mei BOK

Designation: Research Officer


Name: Hwee Hui LAU

Designation: Senior Research Officer


Name: Larry Sai Weng LOO

Designation: AGS Student


Name: Blaise Su Jun LOW

Designation: PhD Student



Recent Publications

Neo, W.Y.C.#, Ciaramicoli, L.M.#, Soetedjo, A.A.P., Teo, K.K.A.*, and Kang, N.-Y.* (2020). 
A new perspective of probe development for imaging pancreatic beta cell in vivo
Semin Cell Dev Biol, accepted.
#First authors
*Corresponding authors

Kang, N.-Y., Lee, J.Y., Lee, S.H., Song, I.H., Hwang, Y.H., Kim, M.J., Phue, W.H., Agrawalla, B.K., Wan, S.Y.D., Lalic, J., Park, S.-J., Kim, J.-J., Kwon, H.-Y., Im, S.H., Bae, M.A., Ahn, J.H., Lim, C.S., Teo, K.K.A., Park, S.Y., Kim, S.E., Lee, B.C., Lee, D.Y., and Chang, Y.-T. (2020).
Multimodal imaging probe development for pancreatic β-cells: from fluorescence to PET.
J Am Chem Soc., accepted.

Loo, S.W.L., Vethe, H., Soetedjo, A.A.P., Paulo, J.A., Jasmen, J., Jackson, N., Bjorlykke, Y., Valdez, I.A., Vaudel, M., Barsnes, H., Gygi, S.P., Raeder, H.#, Teo, K.K.A.#*, and Kulkarni, R.N.#* (2019). 
Dynamic proteome profiling of human pluripotent stem cell-derived pancreatic progenitors. 
Stem Cells, accepted.  
#Co-senior authors
*Corresponding authors

Amirruddin, N.S.#, Low, S.J.B.#, Lee, K.O., Tai, E.S.*, and Teo, K.K.A.* (2019). 
New insights into human beta cell biology using human pluripotent stem cells.
Semin Cell Dev Biol, accepted.
#First authors
*Corresponding authors

Ng, H.J.N., Tan, W.X., Koh, Y.X., and Teo, K.K.A. (2019). 
Human islet isolation and distribution efforts for clinical and basic research. 
OBM transplantation 3, 1-31.

Ng, H.J.N.#, Jasmen, B.J.#, Lim, C.S., Lau, H.H., Krishnan, V.G.,Kadiwala, J., Kulkarni, R.N., Raeder, H., Vallier, L., Hoon, S., and Teo, K.K.A.(2019).
HNF4A haploinsufficiency in MODY1 abrogates liver and pancreas differentiation from patient-derived iPSCs..
iScience 16, 192-205.
#First authors

Kang, N.-Y.#*, Soetedjo, A.A.P.#, Amirruddin, N.S., Chang, Y.-T., Eriksson, O., and Teo, K.K.A.* (2019).
Tools for bioimaging pancreatic beta cells in diabetes.
Trends Mol Med 25, 708-722.
#First authors
*Corresponding authors
Featured Article
Journal Cover Image

Dirice, E., De Jesus, D.F., Kahraman, S., Basile, G., Ng, R.W.S., El Ouaamari, A., Teo, K.K.A., Bhatt, S., Hu, J., and Kulkarni, R.N. (2019).
Human duct cells contribute to β-cell compensation in insulin resistance. 
JCI Insight 4, 1-14.

Dirice, E., Kahraman, S., De Jesus, D.F., El Ouaamari, A., Basile, G., Baker, R., Yigit, B., Piehowski, P.D., Kim, M.J., Dwyer, A.J., Ng, R.W.S., Schuser, C., Vethe, H., Martinov, T., Ishikawa, Y., Teo, K.K.A., Smith, R.D., Hu, J., Haskins, K., Serwold, T., Qian, W.-J., Fife, B.T., Kissler, S., and Kulkarni, R.N. (2019). 
Increased β-cell proliferation prior to immune-cell invasion prevents progression of type 1 diabetes. 
Nat Metab 1, 509-518.

Nguyen, L., Chan, S.Y., and Teo, K.K.A. (2018). 
Metformin from mother to unborn child – are there unwarranted effects? 
EBioMedicine 35, 394-404.

Ng, H.J.N., and Teo, K.K.A. (2018).
Heterogeneity and cell fate flux in single human pancreatic islet cells.
Cell Death Disease 9, 222.

Teo, K.K.A.*, Lim, C.S., Cheow, L.F., Kin, T., Shapiro, J.A., Kang, N.-Y., Burkholder, W., and Lau, H.H. (2018). 
Single cell analyses of human islet cells reveal de-differentiation signatures. 
Cell Death Discovery 4, 14.
*Corresponding author

Lau, H.H., Ng, H.J.N., Loo, S.W.L., Jasmen, B.J., and Teo, K.K.A. (2018). 
The molecular functions of hepatocyte nuclear factors – in and beyond the liver. 
J Hepatol. 68, 1033-1048.

Loo, S.W.L., Lau, H.H., Jasmen, B.J., Lim, C.S., and Teo, K.K.A. (2018). 
An arduous journey from human pluripotent stem cells to functional pancreatic β-cells.
Diabetes, Obesity and Metabolism 20, 3-13.
Journal Cover Image

Isaac, A.*, Kodali, A.*, Nguyen, L., Teo, K.K.A., Chang, C.W., Karnani, N., Ng, K.L., Chong, Y.S., Gluckman, P.D., and Stunkel, W. (2017). 
Gestational diabetes alters functions in offspring's umbilical cord cells with implications for cardiovascular health. 
Endocrinology 158, 2102-2112.
Selected for Endocrine Society Thematic Issue: Diabetes 2018 (

Valdez, I.A., Dirice, E., Gupta, M.K., Shirakawa, J., Teo, K.K.A.*, and Kulkarni, R.N.* (2016).
Proinflammatory cytokines induce endocrine differentiation in pancreatic ductal cells via STAT3-dependent NGN3 activation.
Cell Reports 15, 1-11. 
*Co-senior and Co-corresponding authors
F1000Prime article recommendation:

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.

Gupta, M.K., Teo, K.K.A., Rao, T.N., Bhatt, S., Kleinridders, A., Shirakawa, J., Takatani, T., Hu, J., De Jesus, D.F., Windmueller, R., Wagers, A.J., and Kulkarni, R.N. (2015).
Excessive cellular proliferation negatively impacts reprogramming efficiency of human fibroblasts.
Stem Cells Transl Med 4, 1101-1108.

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

Dirice, E., Kahraman, S., Jiang, W., El Ouaamari, A., De Jesus, D., Teo, K.K.A., Hu, J., Kawamori, D., Gaglia, J., Mathis, D., and Kulkarni, R.N. (2014). 
Soluble factors secreted by T-cells promote β cell proliferation. 
Diabetes 63, 188-202.

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., and Kulkarni, R.N. (2012). 
Setting sail for glucose homeostasis with the AKAP150-PP2B-anchor. 
EMBO J 31, 3956-3957.

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

Brown, S., Teo, A., Pauklin, S., Hannan, N., Cho, C.H.-H., Lim, B., Vardy, L., Dunn, N.R., Trotter, M.W.B., Pedersen, R., and Vallier, L. (2011). 
Activin/Nodal signalling controls divergent transcriptional networks in human embryonic stem cells and in endoderm progenitors. 
Stem Cells 29, 1176-1185.

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. 
Featured in Faculty of 1000 and Perspective in Cell Stem Cell 8, 363-369.

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

Chng, Z., Teo, A., Pedersen, R.A., and Vallier, L. (2010). 
SIP1 mediates cell-fate decisions between neuroectoderm and mesendoderm in human pluripotent stem cells. 
Cell Stem Cell 6, 59-70.

Vallier, L., Mendjan, S., Brown, S., Chng, Z., Teo, A., Smithers, L.E., Trotter, M.W., Cho, C.H., Martinez, A., Rugg-Gunn, P., Brons, G., and Pedersen, R.A. (2009). 
Activin/Nodal signalling maintains pluripotency by controlling Nanog expression. 
Development 136, 1339-1349.