David J. Sharp, Ph.D.

Assistant Professor
Office: ULL 223
Tel: 718-430-3463
Email: dsharp@aecom.yu.edu

The microtubule cytoskeleton plays essential roles in cell division, development and motility. Numerous diseases, including cancer and a myriad of birth defects, are believed to result from dysfunctions of microtubule-based activities. My research program employs a combination of live-cell and biochemial approaches to elucidate the molecular mechanisms that drive and regulate the functions of the microtubule cytoskeleton. Specific research aims include:

I) The assembly and function of the mitotic spindle. The mitotic spindle is a self-organizing microtubule-based machine that moves and segregates chromosomes into identical daughter nuclei during cell division. We are currently studying the general mechanisms underlying spindle and chromosome dynamics.

II) The molecular dysfunctions that give rise to aneuploidy. Abnormal chromosome segregation results in cells with too many or too few chromosomes (aneuploidy). In turn, an aneuploid subpopulation of cells may not be responsive to the mechanisms that normally regulate their growth and development resulting in a potentially dangerous cell mass (e.g. a tumor). We are currently studying the roles of force generating enzymes, termed microtubule-based motors, in the generation and/or prevention of aneuploidy.

III) Regulation of microtubule polymerization dynamics in cells. The polymerization dynamics of microtubules are tightly regulated to allow cells to rapidly respond to a variety of stimuli. For example, subpopulations of microtubules are selectively destabilized to allow for directional cell motility. We are currently studying how proteins that stimulate microtubule depolymerization, in vitro, are utilized to regulate microtubule dynamics in cells.