- 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
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. R01HL118474: Hyperamylinemia in diabetic heart disease: mechanisms, responses, and prevention
2. R01AG053999: Role of Systemic Amylin Dyshomeostasis in Alzheimer's Disease
3. Alzheimer’s Association Research Grant (VMF-15-363458): Role of Oligomerized Amylin in Vascular Injury and Alzheimer Disease
4. American Heart Association (16GRNT310200): Amylin vasculopathy, a therapeutic target to reduce stroke
1. Hyperamylinemia increases IL-1β synthesis in the heart via peroxidative sarcolemmal injury. 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. Diabetes. 2016 - In press
2.Intraneuronal Amylin Deposition Peroxidative Membrane Injury and Increased IL-1β Synthesis in Brains of Alzheimer's Disease Patients with Type-2 Diabetes and in Diabetic HIP Rats. Verma N, Ly H, Liu M, Chen J, Zhu H, Chow M, Hersh LB, Despa F.
J Alzheimers Dis. 2016 May 5;53(1):259-72. doi: 10.3233/JAD-160047.PMID: 27163815
3. Intracellular Na+ Concentration ([Na+]i) Is Elevated in Diabetic Hearts Due to Enhanced Na+-Glucose Cotransport. Lambert R, Srodulski S, Peng X, Margulies KB, Despa F, Despa S. J Am Heart Assoc. 2015 Aug 27;4(9):e002183. doi: 10.1161/JAHA.115.002183. PMID: 26316524
4. The Mitochondrial Peptidase Pitrilysin Degrades Islet Amyloid Polypeptide in Beta-Cells. Guan H, Chow KM, Song E, Verma N, Despa F, Hersh LB. PLoS One. 2015 Jul 20;10(7):e0133263. doi: 10.1371/journal.pone.0133263. PMID: 26191799
5. Neuroinflammation and neurologic deficits in diabetes linked to brain accumulation of amylin. Srodulski S, Sharma S, Bachstetter AB, Brelsfoard JM, Pascual C, Xie XS, Saatman KE, Van Eldik LJ, Despa F. Mol Neurodegener. 2014 Aug 22;9:30. doi: 10.1186/1750-1326-9-30. PMID: 25149184
6. Cardioprotection by controlling hyperamylinemia in a "humanized" diabetic rat model. Despa S, Sharma S, Harris TR, Dong H, Li N, Chiamvimonvat N, Taegtmeyer H, Margulies KB, Hammock BD, Despa F. J Am Heart Assoc. 2014 Aug 21;3(4). pii: e001015. doi: 10.1161/JAHA.114.001015. PMID: 25146704
7. Diabetic hyperglycaemia activates CaMKII and arrhythmias by O-linked glycosylation.
Erickson JR, Pereira L, Wang L, Han G, Ferguson A, Dao K, Copeland RJ, Despa F, Hart GW, Ripplinger CM, Bers DM. Nature. 2013 Oct 17;502(7471):372-6. doi: 10.1038/nature12537. Epub 2013 Sep 29. PMID: 24077098
8. Amylin deposition in the brain: A second amyloid in Alzheimer disease? Jackson K, Barisone GA, Diaz E, Jin LW, DeCarli C, Despa F. Ann Neurol. 2013 Oct;74(4):517-26. doi: 10.1002/ana.23956. Epub 2013 Jul 12. PMID: 23794448
Pharmacological inhibition of soluble epoxide hydrolase provides cardioprotection in hyperglycemic rats.
9. Guglielmino K, Jackson K, Harris TR, Vu V, Dong H, Dutrow G, Evans JE, Graham J, Cummings BP, Havel PJ, Chiamvimonvat N, Despa S, Hammock BD, Despa F. Am J Physiol Heart Circ Physiol. 2012 Oct 1;303(7):H853-62. doi: 10.1152/ajpheart.00154.2012. Epub 2012 Aug 3. PMID: 22865388
10. Hyperamylinemia contributes to cardiac dysfunction in obesity and diabetes: a study in humans and rats. Despa S, Margulies KB, Chen L, Knowlton AA, Havel PJ, Taegtmeyer H, Bers DM, Despa F. Circ Res. 2012 Feb 17;110(4):598-608. doi: 10.1161/CIRCRESAHA.111.258285. Epub 2012 Jan 24. PMID: 22275486
11. Amyloid oligomer formation probed by water proton magnetic resonance spectroscopy. Walton JH, Berry RS, Despa F. Biophys J. 2011 May 4;100(9):2302-8. doi: 10.1016/j.bpj.2011.03.029. PMID: 21539800