Using genetic tools to determine how diabetes leads to business

Project Title: Dissection of Gene Regulatory Networks underlying Diabetic Retinopathy
Institution: Stanford University
Pathway Project Publications: 1
Moved from Harvard University to Stanford University to start first independent faculty position as Assistant Professor in 2017

Major Accomplishments:

The overall goal of this study is to dissect the gene regulatory networks that underlie diabetic retinopathy, uncover the disease mechanisms, and discover novel ways to improve treatment. Since 2016, we developed new genetic tools and started to investigate how different types of retinal cells respond to diabetes and how they interact with each other and collectively contribute to the early progression of retinopathy.

Specifically, we designed and developed molecular tools that allow for specific labeling and manipulation of retinal Müller glial and endothelial cells in rodent models in vivo. These two types of cells respond to diabetes at early stage of the disease and play key roles in the pathogenesis of diabetic retinopathy. It is thus essential to label and manipulate these cells and study diabetes-induced alterations in a cell type-specific manner in vivo.

By using these tools, we profiled the transcriptional and epigenomic alterations in retinal Müller glial cells and endothelial cells in diabetic mice and rats via next-generation sequencing approaches. Currently, we are analyzing the sequencing results and screening for genes and pathways that are altered by diabetes. Critical and novel pathways have emerged from our analyses. This work provides the foundation for future research to understand how the retina responds to diabetes.

Impact Statement:

Diabetic retinopathy is one of the most common complications of diabetes and the leading cause of blindness among working-age populations. The depressing truth is that we do not have effective treatments for this disease. When vision impairment starts, it is impossible to reverse. Currently available therapies are largely preventive, and effective prevention relies on early diagnosis. However, due to the lack of knowledge of underlying mechanisms responsible for the pathogenesis of diabetic retinopathy, it is difficult to identify patients at high risk of developing retinopathy. The Pathway award is essential for me to pursue studies aimed at dissecting the molecular mechanisms underlying the pathogenesis of diabetic retinopathy. The knowledge gained from this study could lead to the discovery of novel therapeutic targets or biomarkers for treatment and early diagnosis.

Recently, I successfully transitioned to an independent position. I am currently a tenure track Assistant Professor in the Department of Ophthalmology at Stanford University School of Medicine.  This award is instrumental in helping me to complete the transition. It allows me to initiate high-risk, high-reward projects, and provides an excellent foundation for my future research career. I would like to express my sincere gratitude to the Pathway program and donors who made this award possible. Without your generosity and support, it would be very difficult for young scientists like me to pursue my career goals and continue to contribute to diabetes research.