- 459 Wethington Bldg, 900 S Limestone St, Lexington, KY 40536-0200
1988 – 1993: Physics, MSc, University of Bucharest
1993 – 1997: Molecular Physics, PhD, Institute of Physics, Bucharest
1998 – 2000: Natural Sciences, Postdoc, Katholieke Universiteit, Leuven
2000 – 2004: Chemistry and Biological Sciences, Postdoc, University of Chicago
2004 – 2005: Instructor of Research, University of Chicago Medical School
2005 – 2007: Research Assistant Professor, University of Chicago Medical School
2008 - Visiting scientist, Research Center Juelich, Germany
2008 – 2013: Assistant Professor, Pharmacology, University of California, Davis
2013 - 2017 Associate Professor, Pharmacology, University of Kentucky
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.
1. R01 AG057290: Programming amylin secretion to slow brain aging - an animal model
2. R01AG053999: Role of Systemic Amylin Dyshomeostasis in Alzheimer's Disease
3. R01HL118474: Hyperamylinemia in diabetic heart disease: mechanisms, responses, and prevention
4. Alzheimer’s Association Research Grant (VMF-15-363458): Role of Oligomerized Amylin in Vascular Injury and Alzheimer Disease
5. American Heart Association (16GRNT310200): Amylin vasculopathy, a therapeutic target to reduce stroke
1. Ly H, Verma N, Wu F, Liu M, Saatman KE, Nelson PT, Slevin JT, Goldstein LB, Biessels GJ, Despa F. Brain microvascular injury and white matter disease provoked by diabetes-associated hyperamylinemia. Ann Neurol. 2017;82, 208-222
2. Liu M, Verma N, Peng X, Srodulski S, Morris A, Chow M, Hersh LB, Chen J, Zhu H, Netea M, Margulies KB, Despa S and Despa F. Hyperamylinemia increases IL-1β synthesis in the heart via peroxidative sarcolemmal injury. Diabetes 2016;65, 2772-83
3. Erickson JR, Pereira L, Wang L, Han G, Ferguson A, Dao K, Copeland RJ, Despa F, Hart GW, Ripplinger CM, and Bers DM, Diabetic Hyperglycemia activates CaMKII and Arrhythmias by O linked Glycosylation. Nature. 2013; 502:372-6
4. Jackson K, Barisone GA, Diaz E, Jin L-W, DeCarli C, and Despa F. Amylin deposition in the brain: a second amyloid in Alzheimer’s disease? Ann Neurol 2013; 74: 517-26
5. Despa S, Margulies K, Chen L, Knowlton A, Havel PJ, Taegtmeyer H, Bers DM, Despa F. Hyperamylinemia contributes to cardiac dysfunction in obesity and diabetes- a study in humans and rats, Circ. Res. 2012; 110: 598-608