Focus: Pancreas development and differentiation, Cellular regeneration, Diabetes
Diabetes is a disease characterized by the progressive loss of insulin-producing beta cells in the pancreas. Individuals with diabetes overcome this beta cell destruction or dysfunction by daily administration of exogenous insulin – a viable and long-standing therapy. However, the long-term complications associated with diabetes are never truly eliminated. Research efforts have therefore moved to the generation of therapeutics that could ultimately fix, not just treat, the beta cell loss. Work in the Mastracci lab uses the mouse and zebrafish model systems to determine how cells in the pancreas develop, differentiate, and regenerate. In particular, we are interested in understanding the signals that are required to produce a healthy pancreas and functional insulin-producing beta cells, with the goal of applying this knowledge to the generation of therapeutics for type 1 diabetes.
Specific scientific areas of focus in the lab include:
Understanding polyamine and hypusine biosynthesis in pancreatic development and disease.
We are investigating key factors in the polyamine and hypusine biosynthesis pathway for their role in the processes of pancreatic and beta cell development, differentiation, and regeneration. The Mastracci lab was the first to describe a role for polyamine and hypusine biosynthesis in the development and differentiation of pancreatic exocrine and beta cells. We are continuing this research and utilizing both the mouse and zebrafish model systems as well as human pancreas tissue provided by the Network of Pancreatic Organ Donors with Diabetes (nPOD) and the Integrated Islet Distribution Program (IIDP).
Determining the signals that induce beta cell regeneration
Zebrafish have several advantages over other model organisms including ease of genetic manipulation, a sequenced genome, rapid external development, high fecundity, extensive regenerative capabilities, and straightforward husbandry. These characteristics make the zebrafish an extraordinary model system for developmental studies, as well as studies that seek to understand cellular regeneration. We are utilizing zebrafish to identify novel pathways that can be targeted with small molecules to induce pancreatic beta cell regeneration. The IBRI Zebrafish Facility is directed by Dr. Mastracci and is being utilized to perform small molecule screens and assess the biology of specific targets to induce pancreatic beta cell regeneration.