The goal of our research is to elucidate the mechanisms that establish cAMP compartmentation in controlling signaling specificity as well as determine the functional importance of cAMP microdomains. cAMP mediates many cellular processes by coupling to downstream effectors such as cAMP dependent protein kinase (PKA) and exchange protein directly activated by cAMP (Epac). Because cAMP is produced at distinct subcellular sites and diffuses rapidly throughout the cell, mechanisms must regulate signal propagation in order to achieve a desired cellular response. However, only recently have tools become available to effectively explore these mechanisms of control. Impaired cAMP signaling has clinical implications such as obesity and type II diabetes. Therefore, a better understanding of cAMP signaling may lead to new therapeutic approaches for these clinical conditions.
The specific aims of our research are to further develop and characterize FRET-based cAMP indicators to elucidate the spatiotemporal dynamics of beta-adrenergic receptor signaling and use these indicators and in vitro assays to determine the downstream effectors and functional significance of mitochondrial cAMP. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DK074381-01
Application #
7062287
Study Section
Special Emphasis Panel (ZRG1-GGG-G (29))
Program Officer
Agodoa, Lawrence Y
Project Start
2006-02-01
Project End
2009-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
1
Fiscal Year
2006
Total Cost
$44,469
Indirect Cost
Name
Johns Hopkins University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Sample, Vedangi; DiPilato, Lisa M; Yang, Jason H et al. (2012) Regulation of nuclear PKA revealed by spatiotemporal manipulation of cyclic AMP. Nat Chem Biol 8:375-82
DiPilato, Lisa M; Zhang, Jin (2009) The role of membrane microdomains in shaping beta2-adrenergic receptor-mediated cAMP dynamics. Mol Biosyst 5:832-7
Dunn, Timothy A; Wang, Chih-Tien; Colicos, Michael A et al. (2006) Imaging of cAMP levels and protein kinase A activity reveals that retinal waves drive oscillations in second-messenger cascades. J Neurosci 26:12807-15
DiPilato, Lisa M; Zhang, Jin (2006) FRETting mice shed light on cardiac adrenergic signaling. Circ Res 99:1021-3