Associate Professor of Systems Biology and of Medicine and of Health Sciences and Technology
Harvard Institutes of Medicine
4 Blackfan Circle
Boston, MA 02115
Lab Size: Between 5 and 10
Jagesh's lab is interested in the general principles of how cells make measurements. Unlike modern day engineered devices, cells make measurements with exquisite precision in an environment of poor signal to noise. Understanding these principles means looking at a variety of systems. His lab focuses on a number of intracellular and extracellular measurement systems.
1) Spindle assembly checkpoint: Watching cells go through mitosis is a mind-boggling event. So many chemical and physical events must be carefully orchestrated to properly segregate the genome. We are interested in the events leading up to the segregation of the chromosomes. How does the cell know that the chromosomes, floating around in the cytoplasm, have all become attached to the mitotic spindle before activating the segregation machinery, also know as anaphase? We are using microscopic imaging, fluorescence correlation spectroscopy and computational modeling to dissect how the cell measures the kinetochore attachment state and makes the decision to execute anaphase.
2) Neutrophil Chemotaxis: The classic cellular measurement problem. How do cells orient themselves in a chemical gradient ? We are using microfluidics to generate quantitative environments for chemotaxing cells. Through microscopy and modeling, we are beginning to understand how cells can make measurements of their environment and compute the direction of travel.
3) Primary Cilia: Almost every one of your cells has a single solitary microtubule-based cilium. It does not move, but without it many of the classical signaling pathways don't function correctly. We are studying the role this organelle plays in determining left-right asymmetry in vertebrates and polycystic kidney disease in humans. How do defects in this organelle lead to defective measurement and disease? Using our favorite tool - microscopy - we are monitoring the signaling events in the cilium and building models for understand signal amplification and integration through this unique organelle.
Czarnecki, P.G. & Shah, J.V. (2012). The ciliary transition zone: from morphology and molecules to medicine. Trends in Cell Biology, 22(4), 201-10. PMID: 22401885.
Hagan, R.S., Manak, M.S., Buch, H.K., Meier, M.G., Meraldi, P., Shah, J.V., & Sorger, P.K. (2011). p31comet acts to ensure timely spindle checkpoint silencing subsequent to kinetochore attachment. Molecular Cell Biology, Epub ahead of print. PMID: 21965286 .
Aboualaiwi, W.A., Ratnam, S., Booth, R.L., Shah, J.V., & Nauli, S.M. (2011). Endothelial cells from humans and mice with polycystic kidney disease are characterized by polyploidy and chromosome segregation defects through survivin down-regulation. Human Molecular Genetics, 20(2), 354-67. PMID: 21041232. PMCID: PMC3005905.
Kwiatkowski, N., Jelluma, N., Filippakopoulos, P., Soundararajan, M., Manak, M.S., Kwon, M., Choi, H.G., Sim, T., Deveraux, Q.L., Rottmann, S., Pellman, D., Shah, J.V., Kops, G.J.P.L., Knapp, S., & Gray, N.S. (2010). Small Molecule Kinase Inhibitors Provide Novel Insight into Mps1 Cell Cycle Function. Nature Chemical Biology, 6(5), 359-68.