Translating disease research into novel therapies

Diabetes trailblazers

Assistant Investigators Andrew Templin, PhD, Michael Kalwat, PhD, and Li Zhang, MD, PhD, from the IBRI’s Lilly Diabetes Center of Excellence.

In 2020, we established three new labs that are led by assistant investigators Andrew Templin, Michael Kalwat and Li Zhang. These labs are part of the IBRI Diabetes Center, which is led by Decio Eizirik, MD, PhD, and Robert Considine, PhD, and are in addition to the Flak Lab.

The Templin Lab focuses on understanding molecular mechanisms that underlie the relationship between islet immune responses and beta cell dysfunction and death in the setting of diabetes. Dr. Templin and his team place emphasis on the concept that beta cell intrinsic properties are central drivers of islet inflammation and immune responses, and together these promote the progressive beta cell dysfunction and loss that lead to diabetes.

The Kalwat Lab is investigating the molecular mechanisms underlying pancreatic islet beta cell function in health and in type 1 and type 2 diabetes. Dr. Kalwat’s team uses a combination of approaches including small molecule and genetic high-throughput screening, as well as genetically-encoded biosensors to gain knowledge about beta cell function. Identifying new pathways and targets is necessary to develop therapeutics that protect and restore the function of these cells in diabetes.

The Zhang Lab is researching the pathogenesis of islet autoimmunity and antigen-specific immune interventions for treating type 1 diabetes (T1D). Over the last decade, Dr. Zhang and her collaborators have worked to understand the pathogenesis of T1D and explored an effective immune intervention to halt or postpone the development of the disease using spontaneous diabetic mouse models. The Zhang Lab will continue to identify more advanced antibody and cell therapies to benefit T1D patients and high-risk individuals.

Indianapolis’ first iPSC Core 

An expression of beta-3-tubulin in ectodermal cells generated from the IBRI’s iPSC Core Lab.

We marked the opening of Indianapolis’ first induced Pluripotent Stem Cell (iPSC) Core in 2020. The stem cells we work with are adult cells that are modified and are derived from skin or blood cells and then reprogrammed into other human cells. 

We are using the iPSC Core to better understand the pathogenesis of T1D by generating human beta cells and neurons. For example, the iPSCs we generate can synthesize and secrete insulin and be used to screen for new drugs that may protect beta cells early in the disease and therefore slow the progression of diabetes.

We also can complete CRISPR-Cas9 screening based on iPSC-derived beta cells and immortalized beta cell lines and are working to generate co-cultures of iPSC-derived beta cells with specific genetic modifications and immune cells. The capabilities of the iPSC Core allow us to work with researchers around the world—and right here at home—to create the cells needed to identify novel drugs and other treatments.

Drug repurposing for type 1 diabetes

Senior Research Associate Donalyn Scheuner, PhD, works with Postdoctoral Fellow Olivia Ballew, PhD in the iPSC Core Lab.

In partnership with Eli Lilly and Company/Lilly Research Laboratories and Dr. Carmella Evans-Molina’s team at the Indiana University School of Medicine, we initiated a project aimed at evaluating immune modulators for their potential to protect beta cells in models of T1D. 

We also are working with the Lilly team to decipher the potential role for the central nervous system in weight loss due to multi-incretin agonists.