Jeff Mumm

Personal Information
Title Assistant Professor
Expertise All Complications
Institution Augusta University
Data Summary
Grants/SubContracts 1
Progress Reports 1
Publications 1
Protocols 0
Committees 1


Novel Model System for Monitoring Multiple Diabetic Complications in Tandem
ABSTRACT Diabetes mellitus is a disease of metabolic dysregulation arising from a lack of glycemic control. Initial exposure to hyperglycemia can have long-lasting deleterious effects even after glycemic control has been achieved. Thus, diabetic patients remain susceptible to developing a number of debilitating complications including peripheral neuropathy, nephropathy, vasculopathy, cardiomyopathy, and retinopathy. Accordingly, there is a need for improved diagnostics aimed at early detection of, and targeted therapeutics for, diabetic complications. Evidence suggests that cellular pathologies often precede other diagnostic methods for detecting diabetic complications. Unfortunately, rodent models of diabetes are often resistant to developing overt cellular pathologies despite displaying metabolic disorder. Thus, establishing systems that can better model diabetic complications could lead to improved diagnostics, enhanced therapeutic strategies, and better quality of life for diabetic patients. Our goal is to establish a battery of novel preclinical models that will facilitate the identification of compounds that delay, ameliorate, or reverse the progression of diabetic complications. We have established novel transgenic diabetes models in zebrafish that allow us to monitor the course of hyperglycemia-induced cellular pathologies directly using high-resolution in vivo confocal microscopy or whole fish histology. Using these resources, we will establish a series of diagnostic metrics for the onset and progression of tissue damage following induction of hyperglycemia. Next, we will evaluate our novel zebrafish models within the context of diabetes-related drug discovery; existing drugs will be tested for the capacity to maintain healthy tissue profiles in diabetic models. We have two specific aims: Aim 1) Validate zebrafish models for monitoring multiple diabetic complications. The onset of different cellular pathologies, e.g., loss of corneal innervation, accumulation of dying cells, neovascularization, will be monitored in living fish and compared between controls, type 1, and type 2 diabetes models. Disease onset and progression will be correlated to relative glucose levels using a novel non-invasive transgenic method and/or direct glucose measurements. Aim 2. Test current therapies for the ability to slow or reverse progression of diabetic complications. We will determine the degree to which currently available drugs serve to ameliorate diabetic complications in transgenic fish. Follow-up studies, will utilize the assays and metrics established here as a means of testing larger compound libraries for entities that ameliorate or reverse diabetic complications in our model system. The proposed studies will result in a useful new preclinical system for monitoring multiple diabetic complications during chemical compound screens. A whole organism-based screening platform provides many inherent benefits to the drug discovery process, not the least of which is the capacity to determine a compounds effect on complex disease phenotypes. The proposed system should thus have a profound impact, potentially leading to the development of new and transformative therapies for eliminating the burden of diabetic complications.

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