Patient-specific hiPSCs for understanding diabetes disease mechanisms

  • Independent Fellow, IMCB, A*STAR and Adjunct Assistant Professor at SBS and LKCMedicine, NTU, and NUS Medicine
      Adrian Teo is an Independent Fellow at IMCB and an Adjunct Assistant Professor at NTU and NUS. He obtained his B.Sc. (1st Class) from NUS and then worked on human pluripotent stem cells (hPSCs) with Ray Dunn, Ph.D., and Alan Colman, Ph.D., at ES Cell International Pte. Ltd. followed by IMB. In April 2008, he joined the laboratory of Ludovic Vallier, Ph.D., at the University of Cambridge to pursue his Ph.D., under the AGS(O) scholarship. Concurrently, he was also an Honorary Cambridge Commonwealth Trust Scholar. 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. During his fellowship, he obtained HSCI seed grants and a JDRF fellowship to pursue his research interests in using hPSCs for in vitro disease modelling of diabetes. He currently runs the Stem Cells and Diabetes Laboratory with a major focus on differentiating human pluripotent stem cells (hPSCs) into pancreatic cells and cell types affected in diabetic complications to dissect the pathology of diabetes and its complications


    Diabetes is a debilitating chronic disease that is spirally out of control. Fundamentally, the progressive failure of pancreatic beta cells results in decreased insulin secretion, ultimately giving rise to hyperglycaemia and overt diabetes. Given that there is a lack of access to pancreatic islets from diabetic patients with defined gene mutations or variants, the use of diabetic-patient-specific human induced pluripotent stem cells (hiPSCs) and their differentiation into pancreatic beta-like cells will provide an inexhaustible source of material for 1) in vitro disease modelling to study diabetes-related mechanisms, 2) developing small molecules that can enhance human beta cell replication and even 3) transplantation therapy.

    Here, I will highlight our efforts in recruiting various types of diabetic patients, obtaining skin biopsies or peripheral blood mononuclear cells (PBMCs), deriving hiPSCs from these somatic cells and differentiating them into pancreatic cells. I will also provide an example of subjecting these diabetic-hiPSCs through a pancreatic differentiation protocol for in vitro disease modelling of diabetes. Overall, it will be evident that disease modelling of human diabetes via the use of diabetic-hiPSCs will provide novel insights into the development of diabetes and its complications.

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