Skip to main content
Department of Pharmacology

Department of Pharmacology

Florin Despa, Ph.D.

Florin Despa, Ph.D.

Assistant Professor
Ph.D., Institute of Physics
Bucharest, 1997
(530) 752-4440

Recent/Current Research Funding

National Science Foundation

American Heart Association

Vision Grant from the UC Davis Health System

UC Davis Alzheimer’s Disease Pilot Research Program

American Diabetes Association

Graduate Group Affiliations

Biomedical Engineering

Molecular, Cellular, and Integrative Physiology

Pharmacology and Toxicology

Research Interests

My laboratory utilizes biochemical, biophysical, molecular, and computational approaches to decipher the links of hyperamylinemia and amylin oligomerization with the cardio-cerebrovascular diseases.

Hyperamylinemia is common in obesity and insulin resistance, causes amylin oligomerization and cytotoxicity, and is known to contribute to the depletion of β-cell mass and development of type-2 diabetes. We have shown, for the first time, that hyperamylinemia also affects the vascular system and tissue of the heart and brain. We found large amylin oligomers, fibrils, and plaques in failing hearts from obese and type-2 diabetes patients, but no deposits in non-failing hearts or in failing hearts from lean, non-diabetic individuals. In the brain, our data show that amylin builds up mainly in capillaries and pericapillary spaces. Amylin plaques and areas of co-localization with β-amyloid, the hallmark of Alzheimer’s disease, occurred also in brain tissues. We use human tissues and a “humanized” rat model of hyperamylinemia to investigate early mechanisms underlying oligomerization of amylin in the secretory pathway, secretion of oligomeric amylin in the blood, and accumulation in heart, kidneys, and brain. Using the rat model of human hyperamylinemia, we found that accumulation of oligomeric amylin contributes to the cardio-cerebrovascular risk by inducing inflammatory and oxidative stress.

On another front, we are trying to identify ways to prevent/ reduce the cytotoxicity of hyperamylinemia and amylin oligomerization. Our recent studies suggest that pro-fibrinolytic molecules may limit amylin deposition and its deleterious effects in the heart. These studies are done in collaboration with other laboratories from UC Davis and outside our campus. Based on these initial data, we propose that the oligomeric amylin is a key contributor to the multifactorial pathogenesis of diabetic cardio-cerebrovascular disorders and that mitigating amylin oligomer accumulation will lower the risk and delay the onset of these diseases.

Relevant Publications

Despa S, Margulies KB, Chen L, Knowlton AA, Havel PJ, Taegtmeyer H, Bers DM, Despa F. Hyperamylinemia contributes to heart dysfunction in obesity and diabetes, a study in humans and rats. Circ Res. 110:598-608 (2012).

K Guglielmino, K Jackson, TR. Harris, V Vu, G Dutrow, JE Evans, J Graham, BP Cummings, PJ Havel, N Chiamvimonvat, S Despa, BD Hammock, F Despa. Pharmacological inhibition of soluble epoxide hydrolase preserves cardiac myocyte structure and function in hyperglycemic rats. Am J Physiol Heart Circ Physiol. (2012) – In Press

Walton JH, Berry RS, Despa F. (2011) Amyloid oligomer formation probed by water proton magnetic resonance spectroscopy. Biophys J. 100 2302-8.

Ionescu-Tirgoviste C, Despa F. (2011) Biophysical Alteration of the Secretory Track in β-Cells Due to Molecular Overcrowding: The Relevance for Diabetes. Integr. Biol. (Camb) 3 173-9.

Despa, F. (2010) Endoplasmic reticulum overcrowding as a mechanism of beta-cell dysfunction in diabetes.  Biohpys J. 98 1641-8.

Despa F. and Berry RS. (2010) Beta-cell dysfunction under hypeglycemic stress – a molecular model. J. Diabetes Scie & Technol. 4 1447-56.

Despa, F. (2009) Dilation of the endoplasmic reticulum in beta cells due to molecular overcrowding? Kinetic simulations of extension limits and consequences on proinsulin synthesis. Biophys. Chemyst. 140:115.  

Book: Lee, RC., Despa, F., Hamann, K., Editors. Cell Injury: Mechanisms, Responses and Repair. NY Acad. Sci. vol. 1066 (2005).

Patent US20070031955 “Compositions and Methods for Refolding of Denaturated Proteins”.

See: Complete List of Publications 

Recent Current Teaching

Freshman Research Seminar, "What keeps the cell alive"

PHA 199-010 (cm 55196) - Special Course

Selected Honors and Awards

  • 2013 Innovation Award from American Diabetes Association
  • 2010 Vision Grant Award