User:Joshua S. Waitzman
- Joshua S. Waitzman
- Ward 8-321
- Department of Cell and Molecular Biology
- Feinberg School of Medicine, Northwestern University
- Chicago, IL, USA 60611
- Email me through OpenWetWare
I'm an MD/PhD student working in the Rice Lab at Northwestern
- 2007, Sc.B. with Honors in Biophysics, magna cum laude, Brown University
In order to divide and proliferate, a single cell must distribute its chromsomes equally to daughter cells by establishing a microtubule-based spindle. Kinesin-5 is a microtubule motor protein that plays an essential role in aligning this spindle structure. As a hallmark of cancer cells is their increased ability to divide, kinesin-5 and other mitotic motor proteins are promising drug targets for cancer therapy, and ispinesib, a specific inhibitor of kinesin-5, is in Phase II FDA trials for non-small cell lung cancer and glioblastoma multiforme.
Kinesin-5 is believed to be regulated by phosphorylation by both M-Cdk and Wee1, kinases known to play roles in the cell cycle. However, the structural mechanisms of this phospho-regulation are unknown. My work uses structural biology and biochemistry approaches to determine the phosphorylation-dependent changes in kinesin-5. Our group uses Electron Paramagnetic Resonance (EPR) spectroscopy to monitor the freedom of movement of different parts of the kinesin-5 protein, as well as kinetic measurements of the protein's activity. By combining these approaches, we hope to clarify the relationships between structure and activity in kinesin-5 and may be able to guide future drug discovery efforts.
- Waitzman JS, Larson AG, Cochran JC, Naber N, Cooke R, Jon Kull F, Pate E, and Rice SE. The loop 5 element structurally and kinetically coordinates dimers of the human kinesin-5, Eg5. Biophys J. 2011 Dec 7;101(11):2760-9. DOI:10.1016/j.bpj.2011.10.032 |
- Duch J, Waitzman JS, and Amaral LA. Quantifying the performance of individual players in a team activity. PLoS One. 2010 Jun 16;5(6):e10937. DOI:10.1371/journal.pone.0010937 |
- Bauer JH, Chang C, Morris SN, Hozier S, Andersen S, Waitzman JS, and Helfand SL. Expression of dominant-negative Dmp53 in the adult fly brain inhibits insulin signaling. Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13355-60. DOI:10.1073/pnas.0706121104 |