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MOLECULAR & CELLULAR PHARMACOLOGY GRADUATE TRAINING PROGRAM

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Research Interests

All eukaryotic cells contain an elaborate membrane system necessary for the transport and compartmentalization of various proteins and lipids. This architecture permits numerous biochemical and signaling processes to occur simultaneously within specialized organelles. While the core machinery necessary to direct vesicle movement has been largely defined, the regulatory mechanisms that modulate membrane trafficking remain poorly understood. In particular, we are interested in determining how the fates of membrane-associated proteins are regulated by developmental cues. Failure to respond efficiently to such signals can result in a variety of disease states including cancer, neurodegeneration, and diabetes. By combining high-resolution fluorescence microscopy, functional genomics approaches, and in vitro biochemistry, we have been using the nematode Caenorhabditis elegans (C. elegans) to identify critical components necessary for membrane reorganization during development.

C. elegans is a well-established model genetic system that has been in use for more than 40 years. In addition, we have found that the oocyte and early embryo of this metazoan provide an ideal setting for the study of membrane dynamics during early development. Specifically, fertilization triggers a dramatic reorganization of the membrane system that can be visualized in utero. This transition is highlighted by 1) a stereotypical developmental switch that can be exploited as a model for studying changes in membrane trafficking during cell differentiation and 2) a highly reproducible resumption of the cell cycle, permitting an examination of organelle restructuring during both meiosis and mitosis. Importantly, RNA interference (RNAi)-mediated protein depletion in C. elegans is efficient and largely independent of intrinsic protein turnover. Several genome-wide RNAi-based screens have identified the set of ~2100 genes required for embryonic viability, including ~600 genes required for embryo production (i.e. inhibition of these genes results in sterility). After carefully examining this collection of ‘sterile’ genes, we found it to be dramatically enriched with membrane trafficking proteins. Through the characterization of this network, we hope to assemble a comprehensive map of the transport machineries necessary for early development in C. elegans, which are likely to be conserved in higher eukaryotes. Moreover, we will identify how different membrane systems interact to allow for plasticity in transport and membrane reorganization during cell proliferation and differentiation.

Honors & Awards

• Shaw Scientist Award (2010)
• DeLill Nasser Award for Professional Development in Genetics (2006)
• Helen Hay Whitney Foundation Postdoctoral Fellowship (2004-2007)
• National Cancer Institute Training Grant Awardee (1998-2002)
• Harvey Almy Baker Graduate Fellowship, Brown University (1997)
• Inducted into the Sigma Xi Honorary Society (1997)

Molecular & Cellular Pharmacology Graduate Training Program | University of Wisconsin Madison
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