Diabetes is increasingly recognized to be influenced by complex genetic and metabolic factors involving? multiple organs and molecules. A single important molecule may directly or indirectly control the function of? other molecules and multiple tissues. The function of an adult tissue is clearly dependent upon its history,? i.e., its differentiation and development, as well as upon signals emanating from other tissues and the? environment. This Program Project Grant involves five outstanding investigators, each focused on a specific? molecule that regulates development and metabolic function of a specific tissue. Project 1 (Lazar)? addresses the role of resistin, a novel adipocyte-secreted factor (adipokine), in insulin resistance and? atherosclerosis. Project 2 (Ahima) examines the role of the central nervous system in mediating the? metabolic effects of adipokines, focusing on adiponectin, leptin, and resistin. Project 3 (Birnbaum)? investigates the regulation of metabolism by Akt/PKB in beta cell and the brain. Project 4 (Kaestner)? addresses the role of the Foxa family of transcription factors, as well as coactivators, in liver metabolism.? Project 5 (Staffers) focuses on regulation of pancreatic development and differentiation by the? homeodomain transcription factor PDX. Each individual project addresses an important hypothesis using? molecular and genetic tools, including in vivo mutational analysis. A particularly exciting aspect of this? proposal is its tremendous potential for synergism. Frequent interactions will maximize the opportunities for? new discoveries related to obvious or surprising interactions between this variety of molecules and metabolic? tissues. These interactions will be facilitated by a collaborative environment at the University of? Pennsylvania; the close physical proximity of the investigators; an administrative core that coordinates? frequent meetings among the investigators and with scientific visitors; an outstanding morphology core in a? dedicated central space that encourages physical and intellectual interactions via the technical director and? shared personnel; and embryonic stem cell core and metabolic phenotyping cores that facilitate interactions? and rapid dissemination of new results, techniques, and ideas. The proposed studies will address major and? specific questions relevant to diabetes and metabolic diseases. At the same time, the specific investigators,? environment, and format of this proposal facilitate interactions that should enhance the discovery process.? There is an excellent likelihood that advances made by this program project group will have a positive impact? on the epidemics of diabetes and metabolic diseases that are ravaging our society.?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
2P01DK049210-11
Application #
7138747
Study Section
Special Emphasis Panel (ZDK1-GRB-6 (M1))
Program Officer
Sato, Sheryl M
Project Start
2006-09-30
Project End
2011-08-31
Budget Start
2006-09-30
Budget End
2007-08-31
Support Year
11
Fiscal Year
2006
Total Cost
$1,936,395
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
Juliana, Christine A; Yang, Juxiang; Cannon, Corey E et al. (2018) A PDX1-ATF transcriptional complex governs ? cell survival during stress. Mol Metab 17:39-48
Barnoud, Thibaut; Budina-Kolomets, Anna; Basu, Subhasree et al. (2018) Tailoring Chemotherapy for the African-Centric S47 Variant of TP53. Cancer Res 78:5694-5705
Kim, Yong Hoon; Marhon, Sajid A; Zhang, Yuxiang et al. (2018) Rev-erb? dynamically modulates chromatin looping to control circadian gene transcription. Science 359:1274-1277
Plikus, Maksim V; Guerrero-Juarez, Christian F; Ito, Mayumi et al. (2017) Regeneration of fat cells from myofibroblasts during wound healing. Science 355:748-752
Juliana, Christine A; Yang, Juxiang; Rozo, Andrea V et al. (2017) ATF5 regulates ?-cell survival during stress. Proc Natl Acad Sci U S A 114:1341-1346
Ediger, Benjamin N; Lim, Hee-Woong; Juliana, Christine et al. (2017) LIM domain-binding 1 maintains the terminally differentiated state of pancreatic ? cells. J Clin Invest 127:215-229
Jang, Jessica C; Li, Jiang; Gambini, Luca et al. (2017) Human resistin protects against endotoxic shock by blocking LPS-TLR4 interaction. Proc Natl Acad Sci U S A 114:E10399-E10408
Carr, Rotonya M; Dhir, Ravindra; Mahadev, Kalyankar et al. (2017) Perilipin Staining Distinguishes Between Steatosis and Nonalcoholic Steatohepatitis in Adults and Children. Clin Gastroenterol Hepatol 15:145-147
Park, Hyeong Kyu; Kwak, Mi Kyung; Kim, Hye Jeong et al. (2017) Linking resistin, inflammation, and cardiometabolic diseases. Korean J Intern Med 32:239-247
Ackermann, Amanda M; Zhang, Jia; Heller, Aryel et al. (2017) High-fidelity Glucagon-CreER mouse line generated by CRISPR-Cas9 assisted gene targeting. Mol Metab 6:236-244

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