Adrian TEO

Stem Cells and Diabetes

PhD - Stem Cell Biology, University of Cambridge, UK

LinkedIn: https://www.linkedin.com/in/adrian-teo-12061b6/

SUMMARY

Adrian Teo is a Senior Principal Investigator and Deputy Director of the Cell and Molecular Therapy Division at the Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR). He has concurrent joint appointments as Director of Graduate Affairs (Biomedical Research Council), A*STAR Graduate Academy and Assistant Professor at the Department of Biochemistry and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore (NUS).

Adrian obtained his PhD in Stem Cells at the University of Cambridge under the mentorship of Prof Ludovic Vallier and Dr. Norris Ray Dunn. Following his PhD, he joined Dr. Ray Dunn lab at the Institute of Medical Biology, A*STAR. Subsequently, he joined Prof Rohit Kulkarni lab at Joslin Diabetes Center, Harvard Medical School. 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’s lab seeks to leverage on human cell models such as 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 his lab are: 1) Modelling and studying human diabetes disease mechanisms; 2) Developing new therapeutics to improve pancreatic β cell function; and 3) Developing stem cell-based therapies for the treatment of diabetes.

Over his career, Adrian has received numerous prestigious awards and grants. He is also a member of the Oxford and Cambridge Society of Singapore, the International Society for Stem Cell Research (ISSCR) and Stem Cell Society Singapore.

AWARDS & GRANTS

KEY AWARDS

2024: A*STAR Graduate Academy (A*GA) Star Mentor Award
2023: A*STAR Graduate Academy (A*GA) Star Mentor Award
2023: COVID-19 Resilience Medal (CRM)
2022: Graduate Mentor of the Year (GRAMAY) Award
2022: Outstanding Team Presentation – The Interstellar Initiative Alumni Program (Japan Agency for Medical Research & Development (AMED) and New York Academy of Sciences)
2021: Public Sector Transformation (PST) Awards
2021: One Public Service Award for contribution as Procurement Lead/OIC, Stronghold Diagnostics Laboratory (SDL), A*STAR
2021: Firefly Awards - Borderless Award (Gold) for contribution as Procurement Lead/OIC, Stronghold Diagnostics Laboratory (SDL), A*STAR
2019: A*STAR Dedicated Service Award
2019: Junior Chamber International (JCI) Ten Outstanding Young Persons (TOYP) of Singapore Honoree Award – Medical Innovation
2018: Stem Cell Society Singapore (SCSS) Dr. Susan Lim Award for Outstanding Young Investigator
2017: Outstanding Team Presentation (August) – The Interstellar Initiative (Japan AMED and New York Academy of Sciences)
2017: Outstanding Team Presentation (March) – The Interstellar Initiative (Japan AMED and New York Academy of Sciences)
2013: Juvenile Diabetes Research Foundation (JDRF) Postdoctoral Fellowship
2011: International Society for Stem Cell Research (ISSCR) Travel Award
2008: Honorary Cambridge Commonwealth Trust Scholar
2008: A*STAR Graduate Scholarship – A*STAR-Cambridge Partnership (ACP) PhD Programme

KEY GRANTS

2024: Singapore Therapeutics Development Review (STDR) Pre-Pilot Stream 1 grant call
2024: ARES Enterprise A*VC Funding
2023: Healthy Longevity Catalyst Award (HLCA)
2023: National Medical Research Council Open Fund-Large Collaborative Grant (NMRC OF-LCG)
2023: GAP Project Award
2022: FY2022 Interstellar Initiative Beyond (Co-I: Adrian Teo, Ph.D.)
2022: National Medical Research Council Open Fund-Young Individual Research Grant (NMRC OF-YIRG) (Co-I: Adrian Teo, Ph.D.)
2022: SingHealth Duke-NUS Genomic Medicine Centre Seed Grant
2022: National Medical Research Council Open Fund-Individual Research Grant (NMRC OF-IRG)
2021: Paris-NUS Research Proposal Grant
2020: 2nd A*STAR-AMED Joint Grant Call
2018: NMRC OF-LCG Seed Funding
2018: Skin Innovation Grant
2018: A*STAR Exploit Technologies Private Limited (ETPL) Gap Funding
2016: NMRC OF-YIRG

RESEARCH

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.

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.

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.

PUBLICATIONS

HNF4A and HNF1A exhibit tissue specific target gene regulation in pancreatic beta cells and hepatocytes
Ng HJN, Ghosh S, Bok CM, Ching C, Low SJB, Chen JT, Lim XHE, Miserendino MC, Tan YS, Hoon S, and Teo KKA.
Nat Commun. 2024 Jun 22;15(1):4288. doi: 10.1038/s41467-024-48647-w. PMID: 38909044; PMCID: PMC11193738
PAX4 loss of function increases diabetes risk by altering human pancreatic endocrine cell development
Lau HH#, Krentz NAJ#, Abaitua F, Perez-Alcantara M, Chan JW, Ajeian J, Ghosh S, Lee Y, Yang J, Thaman S, Champon B, Sun H, Jha A, Hoon S, Tan NS, Gardner DS, Kao SL, Tai ES, Gloyn AL*, Teo AKK*.
Nat Commun. 2023 Sep 30;14(1):6119. doi: 10.1038/s41467-023-41860-z. PMID: 37777536; PMCID: PMC10542369
#First authors
*Corresponding authors
Prioritization of genes associated with type 2 diabetes mellitus for functional studies
T Tan WX, Sim X, Khoo CM, Teo AKK.
Nat Rev Endocrinol. 2023 Aug;19(8):477-486. doi: 10.1038/s41574-023-00836-1. Epub 2023 May 11. PMID: 37169822
Tissue engineering of decellularized pancreas scaffolds for regenerative medicine in diabetes
L Lim LY, Ding SSL, Muthukumaran P, Teoh SH, Koh Y, Teo AKK.
Acta Biomater. 2023 Feb;157:49-66. doi: 10.1016/j.actbio.2022.11.032. Epub 2022 Nov 24. PMID: 36427686
Charting the next century of insulin replacement with cell and gene therapies (Journal Cover Story)
Lau HH#, Gan SU#, Lickert H, Shapiro AMJ, Lee KO, Teo AKK.
Med. 2021 Oct 8;2(10):1138-1162. doi: 10.1016/j.medj.2021.09.001. PMID: 35590204.
#First authors.
Decreased GLUT2 and glucose uptake contribute to insulin secretion defects in MODY3/HNF1A hiPSC-derived mutant β cells
Low BSJ, Lim CS, Ding SSL, Tan YS, Ng NHJ, Krishnan VG, Ang SF, Neo CWY, Verma CS, Hoon S, Lim SC, Tai ES, Teo AKK.
Nat Commun. 2021 May 25;12(1):3133. doi: 10.1038/s41467-021-22843-4. PMID: 34035238; PMCID: PMC8149827.
Featured in https://research.a-star.edu.sg/articles/highlights/opening-the-cellular-gates-to-glucose/

TECHNOLOGY DISCLOSURES

Human skin fibroblasts from healthy and type 2 diabetes (T2D) donors
Availability of both healthy and diabetic human skin fibroblasts
Generation of human induced pluripotent stem cells (hiPSCs)
Expertise in generating, culturing and characterizing hiPSCs

Healthy and diabetic-human induced pluripotent stem cells (hiPSCs) for differentiation into relevant cell types for diabetes drug discovery
Availability of both healthy and diabetic-hiPSCs
Differentiation of hiPSCs into pancreatic islet-like cells
Expertise in differentiating hiPSCs into pancreatic islet-like cells

Differentiation of hiPSCs into mesenchymal stromal cells (MSCs) and then adipocytes
Expertise in differentiating hiPSCs into MSCs and adipocytes

Generation of diabetes mouse models and in vivo transplantation of cells
Expertise in generating diabetes mouse models and transplantation of cells in vivo

Evaluation of glucose metabolism in hepatocytes
Expertise in evaluating glucose metabolism in hepatocytes

*Please contact A*STAR if you wish to collaborate or license these technologies.

Adrian TEO

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