Florin Despa

Position Title
Assistant Professor

Unit
Department of Pharmacology, School of Medicine

2700 Stockton Blvd./2407
Bio

Profile Introduction

Islet amyloid polypeptide - direct molecular link between type-2 diabetes mellitus and heart failure, hydrophobic interactions, molecular crowding effects

Research Interests

Dr. Despa's recent work is focused on 1) understanding how chronic hyperglycemic conditions trigger the impairment of the insulin and islet amyloid polypeptide (IAPP) secretory lines in pancreatic ß-cells and 2) identifying the consequences of this impairment on the heart function. Dr. Despa's studies suggest that prolonged hyperglycemic conditions, which stimulate ß-cells to increase the biosynthesis of insulin (and IAPP!), can generate molecular crowding effects in the early part of the secretory track. Molecular crowding in the endoplasmic reticulum (ER) favors protein denaturation, leading to chemical stress in the ER and gradual dysfunction of the ß-cell. Moreover, the increased secretion of IAPP in the blood, which inherently accompanies the boost in insulin biosynthesis, favors the formation of IAPP preamyloid oligomers. These toxic amyloidogenic entities can accumulate in the heart, causing major cardiac dysfunction. Data from Dr. Despa's laboratory show that IAPP is implicated as a direct molecular link between type-2 diabetes mellitus and heart failure.

Islet amyloid polypeptide - direct molecular link between type-2 diabetes mellitus and heart failure, hydrophobic interactions, molecular crowding effects

Labs

  • Department of Pharmacology, Genome Building, Room 3605
    • Laura Flavia Andronic, undergarduate studentPhung Thai, undergraduate student

Honors and Awards

  • 2008 award for outstanding scientific work in clinical sciences from Romanian Medical Association
  • Research grant from American Heart Association (09BGIA2220165)

    Professional Societies

    • American Heart Association
    • Biophysical Society

    Degrees

    • 1997 PhD Physics Institute of Atomic Physics

    Publications

    (Selected Publications) F. Despa, A. Fernandez and R.S. Berry, Dielectric modulation of biological water, Phys. Rev. Lett. 93, 228104 (2004) (featured in Nature 432 688 2004)

    F. Despa and R.S. Berry, Hydrophobe-water Interactions: Methane as an example, Biophys. J. 95 4241-4245 (2008)

    F. Despa, Water confined in reverse micelles – Probe Tool in Biomedical Informatics, Phys. Chem. Chem. Phys 10 4740-4747 (2008)

    Despa F, Fernandez A, Berry RS, Levy Y, Jortner J. Interbasin Motion Approach to Dynamics of Conformationally Constrained Peptides. J. Chem. Phys. 118 5673 (2003), selected for the Virtual Journal of Biological Physics Research, March 15 2003, R. Austin, ed.

    F. Despa, D.P. Orgill and R.C. Lee, Effects of Crowding on the Thermal Stability of Heterogeneous Protein Solutions, Ann. Biomed. Eng. 33 1125-1131 (2005)

    F. Despa, Biological water, its vital role in macromolecular structure and function., Ann. N.Y. Acad. Sci. 1066 1-11 (2005)

    R.C. Lee, F. Despa, L. Guo, P. Betala, A. Kuo, P. Thiyagarajan, Surfactant Copolymers Prevent Aggregation of Heat Denatured Lysozyme., Ann. Biomed. Eng. 34 1190-1200 (2006)

    F. Despa and R.S. Berry, The origin of long range attraction between hydrophobes in water Biophys. J 92 373-378 (2007)

    F. Despa, Water confined in reverse micelles – Probe Tool in Biomedical Informatics, Phys. Chem. Chem. Phys 10 4740-4747 (2008)

    F. Despa and R.S. Berry, Hydrophobe-water Interactions: Methane as an example, Biophys. J. 95 4241-4245 (2008)

    F. Despa, Fernandez A, Scott R, Berry RS. Hydration Profiles of Amyloidogenic Molecular Structures. J. Biol. Phys. 34 577-590 (2008)

    F. Despa, Dilation of the endoplasmic reticulum in beta cells due to molecular crowding? Kinetic simulations of extension limits and consequences on proinsulin synthesis. Biophys. Chemist. 140: 115-121 (2009)

    Despa S, Chen L, Cummings B, Havel PJ, Margulies KB, Knowlton AA, Bers DM, Despa F, Cardiac Consequences of Increased Amylin Secretion in Diabetics, (2009) Circulation – accepted.

    Book: R.C. Lee, F. Despa and K. Hamann, Editors, “Cell Injury: Mechanisms, Responses and Repair” (2005) N. Y. Acad. Sci. vol. 1066

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