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
My research program examines the mechanisms by which dysregulation of the satiety hormone amylin contributes to neurodegenerative diseases, aiming to inform the development of targeted therapeutic strategies. To this end, we integrate molecular and cellular analyses of human tissues with in vivo approaches that manipulate the amylin gene and assess resulting phenotypes. Over the past 15 years, through collaborative NIH-funded projects involving several Alzheimer’s Disease Research Centers (ADRCs), we have identified dysregulated pancreatic amylin as a contributing factor to Alzheimer’s pathology in both sporadic and familial, early-onset forms of the disease. To mechanistically define amylin pathobiology in a physiologically relevant context, we developed and utilized “humanized” laboratory models that closely recapitulate the molecular and cellular features of human AD. Using conditional knock-in mice with tamoxifen-inducible, β-cell-specific expression of human amylin, as well as inducible knockdown models for endogenous amylin, we investigate how modulation of circulating amylin, and its entry into the brain, regulates cAMP-PKA-mediated glycolysis, tau phosphorylation, and tau-Aβ interactions. To advance therapeutic development targeting amylin pathology, we have generated a polyclonal antibody that selectively neutralizes circulating amylin without disrupting pancreatic function. In contrast to current tau- and Aβ-directed approaches that require direct CNS penetration, our strategy acts upstream via the amylin-cAMP-PKA axis, thereby circumventing structural and localization barriers.
Grants:
- R01NS116058; Despa F (PI); “The Amylin Dyshomeostasis Hypothesis of Vascular Contributions to Cognitive Impairment and Dementia (VCID)”
- Alzheimer’s Association grant ABA-25-1376326 ; Despa F (PI) ; ”Role of APOE in Diabetes-Related Risk for AD”
- Alzheimer’s Association 24AARF-1244535 – Career Development Grant, Deepak Kotiya, PI; Role: Mentor; “Passive amylin immunotherapy in APP/PS1 mice”
- AHA – Carrer Development Grant, Nirmal Verma, PI; Role: Mentor; “Role of Diabetes-Associated Hyperamylinemia in Stroke”
Selected Publications
1. 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
2. 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
3. Ly H, Verma N, Sharma S, Kotiya D, Despa S, Abner EL, Nelson PT, Jicha GA, Wilcock DM, Goldstein LB, Guerreiro R, Bras J, Hanson AJ, Craft S, Murray AJ, Biessels GJ, Troakes C, Zetterberg H, Hardy J, Lashley T, AESG and Despa F. The association of circulating amylin with β-amyloid in familial Alzheimer’s disease. Alzheimer’s Dement. 2021;7:e12130
4. Verma N, Velmurugan GV, Winford E, Coburn H, Kotiya D, Leibold N, Radulescu L, Despa S, Chen KC, Van Eldik LJ, Nelson PT, Wilcock DM, Jicha GA, Stowe AM, Goldstein LB, Powel DK, Walton JH, Navedo MF, Nystoriak MA, Murray AJ, Biessels GJ, Troakes C, Zetterberg H, Hardy J, Lashley T, Despa F. Aβ efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas. Commun Biol. 2023 Jan 3;6(1):2
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. 110 598-608 (2012)
6. Erickson JR, Pereira L, Ferguson A, Dao K, Despa F, Hart GW, and Bers DM Diabetic Hyperglycemia activates CaMKII and Arrhythmias by O linked Glycosylation. Nature. 2013; 502:372-6
7. 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
8. Verma, N., Liu, M., Ly, H., Loria, A., Campbell, K.S., Bush, H., Kern, P.A., Jose, P.A., Taegtmeyer, H., Bers, D.M., Despa S, Goldstein LB, Murray JM and Despa F. Diabetic microcirculatory disturbances and pathologic erythropoiesis are provoked by deposition of amyloid-forming amylin in red blood cells and capillaries. Kidney Int. 97, 143-155 (2020)