Research Description
Type 2 diabetes (T2D) mellitus represents the most common diabetes forms and have been imposing an increasing threat and burden of global public health. Thousands of T2D loci and associated genes have been linked to the increased risk of T2D. However, primarily owing to lack of powerful systems to provide reliable information on the precise roles of T2D-associated genes in the T2D progression, the progress in translating these genetic findings into disease biology has been relatively slow. In this proposed project, we will build on the recent advances of genome-wide association studies (GWAS) and gene-editing technology. We will use human pluripotent stem cells (hPSCs) to establish a robust platform facilitating interrogation of functional roles and complex interactions of multiple T2D-associated genes in the dysfunctions of human pancreatic beta cells. We expected to use this platform to provide novel insights into the molecular mechanisms on how implicated allele mutations mediate increased risk of T2D and further pave the way to identify candidate drugs potential to prevent and cure type 2 diabetes.Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?This proposed project is designed to study the diabetogenic roles and interactions of multiple GWAS-identified genes in human pancreatic beta cells. Completion of this project will provide useful information on the molecular mechanism of at least 20 GWAS-identified genes in the pathogenesis of T2D. This is potential to be transformed into clinical application in T2D therapy and contribute to finding the way to cure T2D patients carrying associated mutations.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?In this proposed project, we will interrogate the interactions among multiple T2D-associated genes and identify their central mechanism in the T2D progress, which would provide new insights into the complex genetic architecture of T2D and promote diagnosis, prevention, and treatment of diabetes. Besides, we will also pinpoint and validate the causal hub genes both in vitro and in vivo. This would pave the way to develop potent T2D drugs to improve the lives of people suffering T2D. Finally, success of this proposed studies will suggest a powerful strategy to interrogate associations among multiple risk genes, which could be extended to more T2D-asscociated genes and even other T2D-asscociated cell types (eg. Hepatocytes, adipocyte, et. al), thus imposing great significance on promote precision medicine to diagnose and treat people living with diabetes.
Why important for you, personally, to become involved in diabetes research? What role will this award play?Diabetes have been imposing an increasing burden of global public health. My long-term goal is to become a competent scientist devoting to elucidating the mystery of diabetes and finding ways to cure people affected by this disease. This award will help me to complete this promising project and provide new insights into the complex genetic structure of T2D. Considering my academic background knowledge on pharmaceutical science for around 10 years, our finding in this project will be promising to be transformed into clinical application in T2D therapy and contribute to finding the way to cure diabetes.
In what direction do you see the future of diabetes research going?Diabetes is a complicated polygenetic disease. I think derivation of functional beta cells or islet from human stem cells (hPSCs) will continue to evolve as promising tools to dissect diabetes pathology and develop new treatments for diabetes. On the one hand, hPSCs are amenable to genetic modification, which facilitates introduction of desired genetic variants and model genetic defects in beta-cell physiology. On the other hand, hPSC-derived beta cells or islets also could provide a renewable source for beta-cell replacement therapy of diabetes patients.