BBS Faculty Member - Jagesh Shah

Jagesh Shah

Department of Systems Biology, HMS
Renal Division, Brigham and Womens Hospital
Harvard-MIT Division of Health Sciences and Technology

Harvard Medical School
HIM Building, Room 564
4 Blackfan Circle
Boston, MA 02115
Tel: 617-525-5912
Fax: 617-525-5965
Email: jagesh_shah@hms.harvard.edu



Our lab is interested in how cells make measurements. Man-made instruments are designed to maximize signal and reduce noise, but we know much less about how cells extract information about their internal state or external environment. Our lab uses a set of interdisciplinary approaches to examine the molecular events in cells that underlie measurement in a number of key cellular processes. We use a range of microscopy, biochemical and spectroscopy-based techniques to investigate protein function through complex formation, dynamics and localization in living cells. These data are then put together into kinetic computational models that attempt to identify the underlying biochemical circuits that permit high fidelity cellular measurements.

We make use of engineered mammalian cell lines and those derived from transgenic mice to provide unique genetic contexts to probe protein function. Much of the information for protein function is derived from live cell measurements, either through simple widefield fluorescence microscopy or fluorescence correlation and lifetime techniques that yield quantitative interaction data. We also make use of modern techniques in microfluidics and tissue engineering to generate relevant cellular microenvironments.

Specifically we are interested in how cells are able to count the number of unattached chromosomes during cell division. This measurement governs the transition to anaphase and is used to prevent chromosome loss. We are also trying to understand how cells maintain the length of their primary cilium. This is a microtubule-based organelle that has been implicated in a variety of human disease syndromes such as polycystic kidney disease and retinal degeneration. How the primary cilium is assembled and maintained is central to understanding its role in the pathogenesis of disease. Lastly, we are investigating how cells orient and move in a chemical gradient – the process of chemotaxis. Here we are making extensive use of microfluidics technology to precisely control the local environment of the chemotaxing cells and simultaneously monitor their internal signaling pathways.



Last Update: 8/22/2013



Publications

For a complete listing of publications click here.

 


 

Besschetnova, T. Y., E. Kolpakova-Hart, Y. Guan, J. Zhou, B. R. Olsen, and J. V. Shah. 2010. Identification of signaling pathways regulating primary cilium length and flow-mediated adaptation. Curr Biol 20:182-187.

Albrecht, D. R., G. H. Underhill, J. Resnikoff, A. Mendelson, S. N. Bhatia, and J. V. Shah. 2010. Microfluidics-integrated time-lapse imaging for analysis of cellular dynamics. Integr. Biol. 2:278-287.

Kops, G. J. P. L., M. van der Voet, M. S. Manak, M. H. J. van Osch, S. M. Naini, A. Brear, I. X. McLeod, D. M. Hentschel, J. R. Yates, S. Van Den Heuvel, and J. V. Shah. 2010. APC16 is a conserved subunit of the anaphase-promoting complex/cyclosome. J Cell Sci 123:1623-1633.

Ciliberto, A., and J. V. Shah. 2009. A quantitative systems view of the spindle assembly checkpoint. EMBO J 28:2162-2173.



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