This proposed research plan describes a 3 year training program for the development of an academic career. The candidate has completed four years of post-doctoral fellowship training and will expand her training during this time period to progress to an academic position. This proposal will define the role of resistin in obesity-related insulin resistance. Mitchell A. Lazar, M.D., Ph.D. will mentor the applicant's scientific development. Dr. Lazar is a recognized leader in the field of nuclear receptors and adipogenesis. Dr. Lazar is the Chief of Endocrinology, Metabolism and Diabetes and the Director of the Penn Diabetes Center. To enhance the training, the applicant will enlist the expertise of Morris Birnbaum, M.D., Ph.D., Howard Hughes Professor and Rexford Ahima, M.D., Ph.D., assistant professor and Director of the Physiology Core of the Penn Diabetes Center. In addition to performing research, the Principal Investigator will benefit from lectures, seminars, and advisory committee meetings. The proposed research will focus on a newly identified hormone that is secreted from adipocytes and which has been shown to antagonize the effects of insulin. The proposed experiments will entail analyzing components in the insulin signaling cascade downstream of insulin binding to determine the mechanism of antagonism of insulin action by resistin (Specific Aim 1). In order to address the role of resistin in insulin resistance associated with obesity (Specific Aim 2), we will study the in vivo regulation of resistin in several different animal models of obesity. We plan to study obesity models in which leptin signaling is impaired (ob/ob, db/db) and intact (Agouti, Cpe-fat). The proposed research plan will reveal detailed information about resistin's role in obesity and diabetes. The scientific environment of the University of Pennsylvania provides the ideal opportunity for the candidate to develop her career by executing the proposed research while utilizing the expertise and resources of Dr. Mitchell A. Lazar. Such an environment should allow the candidate to maximize her potential to establish herself as an independent investigator.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DK059896-03
Application #
6637171
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2001-08-01
Project End
2004-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
3
Fiscal Year
2003
Total Cost
$94,414
Indirect Cost
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Steppan, Claire M; Wang, Juan; Whiteman, Eileen L et al. (2005) Activation of SOCS-3 by resistin. Mol Cell Biol 25:1569-75
Steppan, Claire M; Lazar, Mitchell A (2004) The current biology of resistin. J Intern Med 255:439-47