SDRC at the forefront of innovation in diabetes research: Highlights from the 2019 Frontiers in Diabetes Research Symposium

The 4th Annual Frontiers in Diabetes Research Symposium organized by the Stanford Diabetes Research Center (SDRC) was held on April 24, 2019 at Berg Hall in the Li Ka Shing Center at Stanford University. The SDRC was founded with the goal of scientific innovation in diabetes research made possible by a world class team of scientists, educators and trainees. Through its annual symposium, the SDRC proudly celebrates the achievements of its members, provides a platform for junior scientists and trainees to present their research alongside distinguished investigators, and most importantly, promotes meaningful interactions between scientists to inspire innovative and collaborative research in diabetes.

Researchers from Stanford, other academic and biotech institutions as well non-profit diabetes organizations gathered together for the day-long symposium, which was organized into four sessions, each focusing on cutting-edge research in a specific aspect of diabetes and pancreas biology.

The symposium began with a Stanford Medicine Grand Rounds Seminar by Dr Seung Kim, Director of SDRC, Professor of Developmental Biology and Medicine (by courtesy). Dr Kim affirmed SDRC’s commitment to foster innovative diabetes research by supporting its vibrant and collaborative scientific community via research cores, enrichment programs and pilot and feasibility grants. He enumerated many of the SDRC’s achievements including high-profile publications, grants, awards and collaborations by members. Dr Kim also credited the hard work and dedication of the research cores that form the supportive backbone of the SDRC, including a robust human and pig islet procurement program, a state-of-the-art immune monitoring program, a genomics core facility to provide cost-effective and high-throughput analytic services, and a clinical tissue procurement effort led by Dr Walter Park focused on establishing a human islet auto-transplantation program at Stanford.

Metabolism and Signaling in Diabetes formed the theme for the first session of the day. Dr Suneil Koliwad, Associate Professor at the Diabetes Center at UCSF spoke about the complex relationship between BMI, fat and insulin resistance in a unique multi-ethnic cohort comprised of Chinese and White Americans. Dr Koliwad noted that BMI does not always predict diabetes risk in the Chinese subjects in his cohort and instead provided evidence for the role of subcutaneous fat fibrosis as an indicator of insulin resistance development.

While on the one hand, obesity and fat-induced inflammation are risk factors for diabetes, on the other, cholesterol-lowering drugs are implicated in increasing diabetes risk. Dr Joshua Knowles, Assistant Professor of Medicine at Stanford discussed preliminary findings from a clinical trial exploring the mechanisms by which statins contribute to diabetes risk and found that non-diabetic patients on statin therapy had a lowered ability to secrete insulin.

Research assistant Joon Tae Kim from Dr Jon Long’s group at Stanford addressed energy homeostasis dysfunction, another piece of the metabolism puzzle in obesity and diabetes. He studies the genetic and molecular regulation of a newly identified class of “anti-obesity” metabolites that promote weight loss by increasing energy expenditure.

Session 2 featured speakers in the field of Bioengineering and Behavioral Sciences including Dr Drew Endy, Professor of Bioengineering at Stanford who began his talk with a direct question to the audience, “What would you like a skin microbe to do with respect to diagnosing or treating diabetes?” Crediting the origin of this novel idea to his graduate student Kaisha Benjamin, Dr Endy led a lively discussion on the logistics of engineering a skin bacterium, Staphylococcus epidermis, to essentially work as a blood glucose sensor. If turning microbes into diabetes diagnosis machines seems like an exciting if distant goal, Dr Bruce Buckingham, Stanford Professor of Pediatrics focused on addressing present-day

problems with hybrid closed-loop insulin pumps. One of the most prevalent problems with the closed-loop system is that patients often forget their pre-meal bolus. “If you forget your pre-meal bolus, (the system) kicks you out of the closed loop” he explained and discussed ongoing strategies that could potentially eliminate the need for the pre-meal bolus, propelling us closer to a fully closed loop system.

Despite the promising reality of soon achieving a fully closed loop pump, the ground realities facing type 1 diabetics from disadvantaged backgrounds present a serious challenge to our ability to care for this population. In the final talk in session 2, Dr Diana Naranjo, Clinical Associate Professor of Psychiatry and Behavioral Sciences at Stanford explained the importance of socioeconomic factors facing type 1 diabetics. She outlined the key features of the Novel Interventions for Children (NICH) program to help these patients and presented the results from case studies in the past year enumerating the positive strides made in the lives of the patients.

The holy grail of regenerative research efforts in diabetes and a cornerstone of the Juvenile Diabetes Research Foundation (JDRF) goals is the creation of a renewable source of insulin-producing beta cells. The symposium’s keynote speaker, Dr Michael German, Justine K. Schreyer Endowed Chair in Diabetes Research; Professor; Clinical Director and Associate Director of the Diabetes Center at UCSF presented a fascinating historical overview of his work and others describing the creation of a spatiotemporal map of key regulators during pancreas and islet development and how this provided a blueprint for our current research efforts directed towards the generation of beta cells from non-beta cells such as embryonic stem cells. “This information has been very useful in mapping the position of any cell in the (pancreas) developmental pathway. Having that map has been very useful in driving embryonic stem cells towards a beta-cell fate”. Dr German also discussed his collaborative work with Dr Susan Fisher at UCSF on the role of the human placenta on beta cell proliferation during pregnancy and its implications for promoting beta cell expansion in diabetes.

A recurring challenge in type 1 diabetes regenerative therapeutics research is the problem of the unrelenting attack by the immune system and the associated inflammation induced damage to the beta cells in the body. Speakers in the afternoon session on Immunology and Islet Transplantation addressed specific aspects of this problem and presented potential solutions. Dr Jon Piganelli, Associate Professor from the University of Pittsburgh spoke about the role of oxidative stress induced inflammation in type 1 diabetes and his efforts to contain the inflammatory damage by using small molecule anti-inflammatory drugs such as Manganese Metalloporphyrins.

Efforts to prevent the development of type 1 diabetes were the focus of Dr Nadine Nagy’s work at Stanford. She demonstrated that Interleukin 2 (IL-2) administration via hydrogels reduces the onset of diabetes in a mouse model of type 1 diabetes by potentiating the induction of protective regulatory T cells (T-regs) and averting beta-cell destruction. Also focusing on T-regs, Dr Garry Fathman, Stanford Professor of Medicine (Emeritus) framed the problem slightly differently, noting that T-regs are functionally defective, making them unresponsive to IL-2 treatment in many cases. He thus sought to restore the function of T-regs as a preventive therapeutic measure to preserve islet function.

Type 1 diabetes diagnosis, pathology and therapeutics ultimately converge on the biology of beta cell and the pancreatic islet which formed the focus of the final session of the symposium titled Pancreas and Islet Biology. Dr Julie Sneddon, Assistant Professor of the Diabetes Center at UCSF sought to develop new regenerative therapeutics through a better understanding of pancreas development. Her work identified a new population of endocrine precursor cells during pancreas development using state-of-the-art single cell RNA-seq to capture cellular heterogeneity.

Dr Linda Yip from the Stanford Department of Medicine demonstrated that beta-cells in mice exposed to high dietary iron were more likely suffer dysregulated iron metabolism and die of iron toxicity. Finally, Dr Haixia Hu, a visiting professor in the Stanford Department of Medicine addressed the problem of severe hypoglycemia in type 1 diabetes by proposing the use of FDA-approved small molecule insulin signaling antagonists.

In addition to the talks, students, postdoctoral scholars, investigators and research core personnel from the SDRC presented their work at the all-day poster session. The SDRC recognized outstanding achievements of its trainees through an awards function at the conclusion of the symposium with prizes for best posters given to Keren Hilgendorf, Owen Jiang and Yunshin Jung. Timothy Horton’s paper “Zinc-Chelating Small Molecules Preferentially Accumulate and Function within Pancreatic beta cells” which was the focus of a feature on the SDRC website and newsletter, won the Diabetes Knowledge Award for advancing innovative and collaborative research in the field.

As in past years, the 2019 Frontiers in Diabetes Research Symposium brought together the brightest scientific minds in pancreas biology and diabetes research, reflecting a vital goal of the SDRC: fostering collaborations among key opinion leaders and stakeholders within the bay area and beyond. It is hoped that the curiosity, interest and discussions generated during the symposium will form the foundation for future collaborative ventures between SDRC members and investigators outside Stanford. The SDRC includes more than 100 members throughout Stanford University.

By
Harini Chakravarthy
Harini Chakravarthy is a science writer for the Stanford Diabetes Research Center.