Daria Mochly-Rosen

Administrative Appointments

• Professor, Department of Chemical and Systems Biology (2001 - present)
• Chief, Division of Chemical Biology (2001 - 2002)
• Chair, Department of Molecular Pharmacology (2002 - 2006)
• Member, Neuroscience Institute at Stanford (2002 - present)
• member, Cardiovasuclar Institute (2004 - present)

Honors and Awards

• The George D Smith Professor of Translational Medicine, School of medicine (2005)
• Reed-Hodgson Professor in Human Biology, Stanford University (1996-2001)

Professional Education

Postdoctoral Advisees

Leslie Cruz,  Inbal Maayan Haimovich,  Andrey Malkovskiy,  Sathish Manickam,  Suresh Palaniyandi,  Nir Qvit

Graduate & Fellowship Program Affiliations

• Cancer Biology
• Chemical and Systems Biology
• Neurosciences
• Cardiovascular Medicine

Internet Links

• Mochly-Rosen Lab Site

Current Research Interests

We are studying the mechanism of protein kinase C-mediated signal transduction in several disease models. Based on our recent data, we proposed a working hypothesis that activated PKC isozymes bind to intracellular receptor proteins located at different subcellular sites, and that these receptors differentially bind specific PKC isozymes. Evidence was obtained for the presence of intracellular receptor proteins that bind activated PKC. Binding of PKC to these proteins was concentration-dependent, saturable and specific, suggesting that these binding proteins are receptors for activated C-kinase, or "RACKs".

We have characterized and cloned several RACKs and identified domains in different PKC isozymes that are required for the specific association with these RACKs; these domains are distinct from the substrate binding site on PKC. On the basis of this information, together with computer modeling of crystal structures of the interacting proteins, we have identified novel isozyme-selective inhibitors that inhibit translocation and the consequent function of individual PKC isozymes. These inhibitors are fragments of PKC or RACKs that have 'dominant negative' activities on PKC binding to RACKs and on their activities, in vivo. In addition, we prepared synthetic peptides corresponding to the binding sites in PKC and RACKs. We are currently determining the effects of these isozyme-selective translocation inhibitors on a number of PKC-mediated cell functions in normal and diseased heart. These include cardiac and smooth muscle cell contraction, gene expression, hypertrophy, and response to and protection from ischemic insult.

Publications

• Identification of εPKC Targets During Cardiac Ischemic Injury. Budas G, Costa Jr HM, Ferreira JC, Teixeira da Silva Ferreira A, Perales J, Krieger JE, Mochly-Rosen D, Schechtman D. Circ J. 2012
• Nitroglycerin use in myocardial infarction patients. Ferreira JC, Mochly-Rosen D. Circ J. 2012; 76 (1): 15-21
• Protein Quality Control Disruption by PKCβII in Heart Failure; Rescue by the Selective PKCβII Inhibitor, βIIV5-3. Ferreira JC, Boer BN, Grinberg M, Brum PC, Mochly-Rosen D. PLoS One. 2012; 7 (3): e33175
• Regulation of cardiac excitability by protein kinase C isozymes. Ferreira JC, Mochly-Rosen D, Boutjdir M. Front Biosci (Schol Ed). 2012: 4 532-46
• A novel aldehyde dehydrogenase-3 activator leads to adult salivary stem cell enrichment in vivo. Banh A, Xiao N, Cao H, Chen CH, Kuo P, Krakow T, Bavan B, Khong B, Yao M, Ha C, Kaplan MJ, Sirjani D, Jensen K, Kong CS, Mochly-Rosen D, Koong AC, Le QT. Clin Cancer Res. 2011; 17 (23): 7265-72