Section: Rotations

Postdoctoral Position Available

Silvia Corvera, M.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Program in Molecular Medicine

Other Affiliation(s):
   Interdisciplinary Graduate Program

Rotation Projects

Our laboratory is interested in understanding the basis of metabolic diseases. It is thought that the modern western diet has given rise to an increase in the metabolic syndrome, which includes hypertension, diabetes, heart disease and also cancer. Using Affymetrix Chip gene arrays we have found that drugs that are used to treat the metabolic syndrome affect the function of adipose cells in several important ways: First, they stimulate the generation of adipocytes with increased mitochondrial content and oxidative capacity (Wilson-Fritch, L., et al, “Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone.” J Clin Invest. 2004 Nov;114(9):1281-9. Second, they stimulate the production by adipocytes of growth factors that increase angiogenesis. This finding may help explain the development of vascular diseases that accompany weight gain. In addition, the production of pro-angiogenic factors by adipocytes could facilitate the development of tumors that has been associated with obesity. To investigate the molecular mechanisms and physiological importance of adipose tissue angiogenesis, we have developed novel mouse and human ex-vivo models and have several possible rotation projects in this exciting new field. One of them involves the further characterization of ANGPTL4, a factor we have identified to be produced by adipocytes and control angiogenesis as well as lipid metabolism. Nobody knows how ANGPTL4 works, because its receptor has not been identified. We wish to use proteomic and gene ablation approaches to identify this receptor, and several aspects of this project are available as rotation projects. They include generating biologically active ANGPTL4 labeled with fluorophores; developing endothelial cell assays to measure ANGPTL4 binding and activity; using shRNA libraries, expression libraries and 2-hybrid screens to identify binding partners for ANGPTL4.

The development of metabolic disease is initiated by alterations in hormone signaling. We have found that signaling from many receptors takes place in endosomes (Hayes ,S., Chawla, A., Corvera, S. “TGF beta receptor internalization into EEA1-enriched earlyendosomes: role in signaling to Smad2.” J Cell Biol. 2002 Sep 30;158(7):1239-49).   Using a siRNA screen in C. elegans, we have recently found a new endosomal FYVE domain containing protein called WDFY2(Hayakawa, A., Murphy, S., Leonard, D., Hayes, S., Soto, M., Fogarty, K.E., Standley, C., Bellve, K., Lambright, D., Mello, C., and Corvera, S. “The WD-40 and FYVE domain containing protein 2 defines a new class of early endosomes essential for endocytosis.” Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11928-33.). Recent experiments indicate that this protein is involved in signaling by binding the serine threonine kinase Akt2. Several aspects of this project are available as rotation projects. They include using high speed, high resolution light microscopy to define the relationship between Akt2 and WDFY2 during signaling, as well as determining the structural features of Akt2 that allow it to bind to WDFY2.

Phone: 508 856 6898
E-mail: Silvia.Corvera@umassmed.edu
Keywords: Intracellular Trafficking, Cell Biology, Signal Transduction

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Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Dr. Corvera for additional details.