One of the goals of the Frontiers in Diabetes Research Symposium is to recognize and celebrate the scientific accomplishments of our SDRC trainees who present outstanding posters.
Dr. Sooyeon Lee studies mitochondrial dysfunction in diabetes. Mitochondria are intracellular organelles, commonly referred to as the ‘powerhouses’ of a cell because of their central role in generating energy through cellular respiration. Abnormal energy metabolism as a result of dysfunctional mitochondria has been argued to be a central contributor to the failure of beta cells to function and the development of type 2 diabetes. “A lot of the mechanisms underlying beta cell failure in diabetes converge upon mitochondrial dysfunction, but how mitochondrial dysfunction leads to diabetes remains a fundamental unanswered question”, says Dr. Lee.
Dr. Lee’s work focuses on elucidating the function of a key mitochondrial protein called Succinate Dehydrogenase (SDHB), an enzyme that is essential for mitochondrial energy production. She and her colleagues found that SDHB was reduced in human diabetic islet tissues. When they deleted SDHB specifically in insulin-producing beta cells in mice, they developed diabetes. Dr. Lee’s investigations showed that the mitochondrial function in the beta cells of these mice was impaired pointing to a clear role for SDHB in maintaining beta cell function.
In thinking about the relevance of her findings to the development of therapeutics, Dr. Lee remarks, “My work focuses on how and why mitochondrial dysfunction occurs. It explains one aspect of the mechanism involved in beta cell failure of diabetes that could be targeted therapeutically”. Dr Lee used the poster award prize to attend a Vanderbilt Islet Biology Workshop last year where she had the opportunity to interact with islet biologists at Vanderbilt University. She is a postdoctoral scholar in Dr. Justin Annes’ laboratory.
Dr. Heshan Peiris and his colleagues built a rapid and efficient screening system to identify and functionally test diabetes risk genes using the power of fly genetics and a novel human islet culture system. This approach identified BCL11A as a master regulator of human insulin secretion in pancreatic beta cells. In explaining the logic of using the fly as an organism to screen for human diabetes risk genes, Dr. Peiris notes, “The fly and more specifically the fly insulin producing cells have striking functional similarity to human pancreatic beta cells. I believe that the fly system holds tremendous potential to identify novel genetic and pharmacological regulators of beta cell function”.
That said, Dr. Peiris admits that the fly screening system, at first, seemed like a huge risk. “When we began our studies, we were unsure if differences or commonalities between flies and humans would dominate. I’m glad to say it seems like the common features are readily detected in our strategy.” To realize this however took quite a bit of work: for example, members of the Seung Kim lab carried out RNA-seq studies on fly insulin producing cells and human islet beta-cells. “This work will provide a complete picture of conserved genetic beta-cell regulation and provide a road-map for future functional studies of diabetes genetics” he says.
Dr. Peiris recently published his work and has gone on to a Principal Scientist position at Tosk, a biotech company in the Bay Area.
By
Harini Chakravarthy
Harini Chakravarthy is a science writer for the Stanford Diabetes Research Center.