Department of Medicine
University of Colorado Denver
MECHANISMS OF INSULIN RESISTANCE:
Grants: 1) Merit Review I: Molecular Mechanisms of ICAM-1 and VCAM -1 Expression in Vascular Cells.
Description of Research
The focus of our research is based primarily on the effects of obesity and its associated risk factors, insulin resistance and hyperinsulinemia, with particular reference to vascular disease and neuro-degeneration. The goals of this lab are to understand the molecular mechanisms involved with the expression of cellular adhesion molecules in the context of atherosclerosis and neuro-degeneration of hippocampal cells in the context of Alzheimer’s Disease (AD). Although it appears that atherosclerosis and AD are two unrelated diseases, we hypothesize that obesity and insulin resistance, along with the concomitant state of hyperinsulinemia, are molecular forces that drive the pathophysiology associated with these two disorders. Moreover, we hypothesize that similar; if not the same key molecular pathways may induce the pathogenesis of these two disparate but devastating diseases. Finally, these studies will strive to determine molecular targets for potential therapeutic interventions for these two destructive and life threatening diseases.
1-2 Most Significant Publications
1) Goalstone, M.L., Leitner, J.W., Wall, K., Dolgonos, L., Rother, K.I., Accili, D., and Draznin, B. (1998). Insulin’s effect on farnesyltransferase: specificity of insulin action and potentiation of nuclear effects of insulin-like growth factor-1, epidermal growth factor, and platelet-derived growth factor. J. Biol. Chem. 273:23892-23896
2) Girish Sharma and Marc L. Goalstone (2007) Regulation of ERK5 by insulin and angiotensin-II in vascular smooth muscle cells. Biochem. Biophys. Res. Commun. 354:1078-1083.
Primary Focus Area (if part of the obesity initiative)
- Our primary area of focus is cardiovascular disease. We are examining the molecular interactions of ERK5 and FTase with other intracellular molecules (e.g., NFkB) that play a predominant part in cellular and tissue inflammatory processes in the vasculature (i.e., atherosclerosis) that result from the presence of hyperinsulinemia in the context of obesity.
Secondary Focus Areas (if part of the obesity initiative)
- Our secondary area of focus is neuro-degeneration. We are investigating the roles of ERK5 and FTase in both the physiology and pathophysiology of neuronal cells in the context of obesity. We hope to determine that these two molecules play important roles in the biochemistry of these cells and can serve as therapeutic drug targets to augment healthy cells or ameliorate dysfunctional cells.
Access to Specialized Populations
· Via collaborators
Benefit of CNRU
The major benefit of the CNRU for me will be the enhanced interaction and collaboration with other CNRU investigators. The core laboratories of the CNRU are going to become critical to my research success not only in process of collaboration, but also in direction of my overall research. These laboratories provide services in a cost-effective manner more than I could develop in my own laboratory. Additionally, I am hoping to generate a sufficient amount of data from my specific research with the assistance of the CNRU to not only publish my findings, but also obtain future funding of my projects as a result of grant applications..
CNRU Cores Used
To enhance my research technology
CNRU CollaborationsMarc-Andre Cornier, Boris Draznin, James O. Hill, Robert Eckel, Jed Friedman, Jane Reusch, Cecilia Wang, Pete Watson