Florin Despa, PhD
Connect
859-218-0291f.despa@uky.edu
Positions
- Professor, Lewis Honors Faculty
College Unit(s)
Other Affiliation(s)
- Nutritional Sciences Graduate Faculty
- Pharmacology and Nutritional Sciences Primary Faculty
- Saha Cardiovascular Research Center
Biography and Education
Education
Education 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 Positions
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
Amylin Diagnostics (AMdx) and Therapeutics for Diabetic Microvascular Disease
Microvascular dysfunction is common in persons with type-2 diabetes and is associated with vascular contributions to cognitive impairment and dementia (VCID). A major scientific goal is to understand whether the same factors contributing to type-2 diabetes pathogenesis affect small blood vessels leading to diabetic microvascular complications. These factors can be used as therapeutic targets to ameliorate (or possibly to reverse) processes underlying diabetic microvascular disease. Accumulating evidence from multiple research teams (including pioneering work from our team) suggests a link between unregulated secretion of the pancreatic hormone amylin and diabetic microvascular injury (brain microhemorrhages, kidney hypoxia and decreased cardiac output), providing a novel therapeutic target to reduce diabetic complications. Given that amylin appears as a potent trigger of cell metabolic reprogramming, amylin dysregulation is a double hit metabolic-microvascular condition. Our Specific Objectives include:
- Integrate clinical and translational science research efforts in diabetes-associated metabolic-microvascular dysfunction;
- Advance the discovery of new treatments for disorders associated with microvascular dysfunction (diabetic cardiovascular & cerebrovascular diseases and cognitive decline).
Grants:
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. R01NS116058: The Amylin Dyshomeostasis Hypothesis of Vascular Contributions to Cognitive Impairment and Dementia (VCID)
Selected Publications
Ly H, Verma N, Sharma S, Kotiya D, Despa S, Abner EL, Nelson PT, Jicha GA, Wilcock DM, Goldstein LB, Guerreiro R, Brás J, Hanson AJ, Craft S, Murray AJ, Biessels GJ, Troakes C, Zetterberg H, Hardy J, Lashley T, Aesg, Despa F. The association of circulating amylin with β-amyloid in familial Alzheimer's disease. Alzheimers Dement (N Y). 2021;7(1):e12130.
2. Verma N, Liu M, Ly H, Loria A, Campbell KS, Bush H, Kern PA, Jose PA, Taegtmeyer H, Bers DM, Despa S, Goldstein LB, Murray AJ, Despa F. Diabetic microcirculatory disturbances and pathologic erythropoiesis are provoked by deposition of amyloid-forming amylin in red blood cells and capillaries. Kidney Int. 2020;97:143-155.
3. 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
4. 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
5. 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
6. 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
7. 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