2016 Pathway Accelerator Awardee Daniel J. Ceradini, MD
Uncovering a new approach to wound healing in diabetes
Project title: Therapeutically Targeting Keap1/Nrf2 Dysfunction in Diabetes
Institution: New York University School of Medicine
Pathway project publications: 2
Serves as a reviewer of grants, manuscripts and conference abstracts
High blood glucose levels associated with diabetes disrupt antioxidant networks important for tissue regeneration. This project seeks to determine whether restoring this critical antioxidant pathway to normal will reverse the impaired tissue regeneration caused by diabetes. To date, we have generated laboratory mice to investigate the role of Nrf2 in each critical cell type during tissue regeneration. The elimination of Nrf2 significantly delayed healing times, mimicking the poor wound healing that occurs in diabetes. We developed a technique to deliver an inhibitor to diabetic wounds that affected stabilization of Nrf2 and markedly accelerated tissue regeneration.
We continue to collect human intact skin and wounds from patients with and without diabetes. Our first grouped analysis revealed important differences between intact skin of people with and without diabetes. Similar differences were noted in wound tissue between people with and without diabetes. Ongoing studies are examining skin samples to further dissect the molecular mechanisms of Nrf2 dysfunction in cells from people with diabetes.
The Pathway award has provided a tremendous opportunity with flexible funding and access to a broad network of diabetes experts in different fields. Having treated numerous patients with diabetes and seemingly unsolvable clinical problems such as non-healing wounds and poor response to ischemic events, I have taken first-hand clinical observations back to laboratory to develop novel therapeutics to address these critical public healthcare problems. As a surgeon scientist, I have a unique perspective on both the molecular science and the more practical aspects about delivering therapeutic agents in a clinical scenario.
The support of the Pathway program has allowed our lab to move forward rapidly in both characterizing fundamental molecular pathways that are impaired in diabetic tissue regeneration, as well as to develop innovative and practical solutions to target such pathways that can be rapidly translated to clinical use. Translational research has been the focus of my academic career to date, and the Pathway award has been instrumental in bringing our efforts to the next level.