Diabetes Research

Developing A First-In-Class Regenerative Therapy for Diabetes

Our goal is to identify, characterize and optimize small molecules that stimulate beta-cell regeneration.

Our principle experimental strategy is to develop and utilize high throughput screening platforms to uncover therapeutic leads, utilize in vitro and in vivo models to develop in depth mechanistic understanding of lead compound function and to deploy medicinal chemistry efforts to optimize lead compounds for in vivo use, i.e. develop new medicines for diabetes!

Lead Compound Discovery

High-Throughput, High-Content Screening

Pancreatic islets are isolated, plated and compound-treated to identify molecules that stimulate beat-cell replication. Automated image aquisition and analysis (Cellomics ArrayScan) are utilized to maximize throughput and eliminate bias. 

Lead Compound Confirmation

Beta-Cells, long thought to be post-mitotic and incapable significant growth, have suprising regenerative capacity. Using small molecule-based phenotypic screening, we have discovered numerous novel stimulators of beta-cell regeneration that induce unprecedented levels of growth. (Above) Beta-cells are identified by the expression of insulin (red) and replication by ki-67 expression (green).  

Lead Compound Characterization

ADK-is are potential diabetes medications. We use a variety of experimental strategies to understand how compounds stimulate beta-cell regeneration. After we discovered Adenosine Kinase  inhibitors (ADK-is) stimulate beta-cell growth, we generated beta-cell-specific ADK Knockout (bADKO) mice. These mice exhibit dramatically improved glucose tolerance.  

Lead Compound Optimization

A major goal of the Annes Lab is to bridge the space between lead compound discovery and the development of drug-like compound series

Using computational structure-based modeling, lead compounds are stragegically derivatized for SAR, target ID studies and compound optimization (potency, efficacy, specificity, pharmacokinetics and tolerability).

Dr. Annes is a Stanford ChEM-H Fellow.