Research in my laboratory is centered on deciphering the pathobiology of the interaction between the pancreatic hormone amylin and components of the cardiovascular and central nervous systems. Particularly, we are interested in the role of oligomerized amylin in triggering signaling events that promote cell pathological remodeling and apoptosis in heart and brain. In our work, we integrate biochemical investigations of human tissues with clinical data, physiological analyses and in vivo phenotyping.
What affords us the ability to identify specific amylin-induced cytotoxicity is the use of a combination of genetically engineered rodent models, including animals overexpressing human amylin in the pancreas and amylin knockout animals. Employing rodent models “humanized” for amylin is conceptually innovative since amylin from rodents is not amyloidogenic and does not accumulate in cells and tissues. Therefore, we are able to examine mechanistically the impact of oligomerized human amylin on heart and brain function in a setting that closely recapitulates the amylin pathology seen in diabetic humans.
The long term goal is to gain insight into the molecular basis by which amylin dyshomeostasis may contribute to the pathological progression of diabetic complications, and how modulation of amylin-mediated processes might be used as a rational basis for new therapeutic strategies.