Physical & Biological Sciences Division
Professor
Faculty
Physical Sciences Building
462
Physical Sciences Bldg 459 (Lab)
Chemistry
B.A. University of Pennsylvania, Philadelphia
Ph.D. UC Berkeley
Molecular basis of telomere length and telomerase-related diseases; biophysical characterization of nucleic acid-associated molecular motors; development of novel approaches for imaging enzymes in cells
Single-molecule Biophysics and Enzymology; Structure, function, and assembly of the telomerase ribonucleoprotein, Fluorescence Resonance Energy Transfer (FRET), optical/magnetic trapping.
Telomeres are specialized chromatin structures that prevent deleterious chromosome fusion events by differentiating normal chromosome ends from sites of DNA damage. Telomere DNA is synthesized by the telomerase ribonucleoprotein (RNP), an enzyme comprised of the telomerase reverse transcriptase, telomerase RNA, and several additional protein cofactors. Telomerase activation is a tightly regulated process restricted to rapidly dividing cell types such as stem cells and the majority of human tumors. It is thus of direct medical importance to understand fundamental mechanisms governing telomerase assembly and function.
My laboratory takes a multi-disciplinary approach to study the structure and function of telomerase, combining established biochemical methods with emerging single molecule techniques which allow direct analysis of complex dynamics not possible with traditional ensemble measurements. For example, we employ single molecule fluorescence resonance energy transfer (smFRET) to monitor telomerase structure and dynamics during RNP assembly and catalysis. In addition, we utilize micro-manipulation techniques such as magnetic trapping to investigate the unique structural properties of telomere DNA and the molecular mechanisms of telomere remodeling proteins that contribute to telomerase regulation.
Students in my laboratory will have the opportunity to participate in diverse areas of research including: molecular biology, protein and nucleic acid biochemistry, design and fabrication of biophysical instrumentation, software development, and quantitative data analysis.