Photo of Jagesh V. Shah,  PhD

Jagesh V. Shah, PhD

Harvard Medical School

Harvard Medical School
Phone: (617) 525-5912
Fax: (617) 525-5965


Jagesh_shah@hms.harvard.edu

Jagesh V. Shah, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • Associate Professor, Health Sciences and Technology, Harvard Medical School
  • Associate Professor, Medicine, Harvard Medical School
  • Associate Professor, Systems Biology, Harvard Medical School
  • Assistant Professor, Renal Division, Brigham And Women's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our lab uses a set of interdisciplinary approaches to observe and measure molecular events that control cell division, or mitosis, and cell polarity – two fundamental processes that are deranged in transformed cells. During mitosis, the control of chromosome segregation is governed by the mitotic checkpoint that prevents aneuploidy and may meditate tumorigenesis. We use fluorescent proteins tagging technologies and microscope-based measurements of protein dynamics in living cells (such as fluorescence correlation spectroscopy and photobleaching methods) to quantitatively dissect checkpoint signaling in mitotic cells. These data have been used to generate a number of experimentally-testable computational hypotheses as to how the checkpoint may function in normal and perturbed states.

The division process is also spatially oriented, particularly in epithelial ductal structures such as the renal tubule and hepatobiliary system. Disturbances in this orientation (i.e. planar cell polarity) have been linked to cilium-based signaling and underlie cystic disease and tumorigenesis (e.g. VHL-mediated RCC). We are studying the links between the primary cilium and mitotic orientation through the development of microtechnology-based in vitro cell culture models to mimic the ductal microenvironment. To this end we have generated a large number of cell lines stably expressing genes involved in cilium-based transport and signaling permitting detailed real-time microscopic analysis of the signaling events in living cells.

Publications

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  • Goldmacher VS, Audette CA, Guan Y, Sidhom EH, Shah JV, Whiteman KR, Kovtun YV. High-affinity accumulation of a maytansinoid in cells via weak tubulin interaction. PLoS ONE 2015; 10:e0117523. PubMed
  • Silva BA, Stambaugh JR, Yokomori K, Shah JV, Berns MW. DNA damage to a single chromosome end delays anaphase onset. J Biol Chem 2014; 289:22771-84. PubMed
  • Courtis AM, Santos SA, Guan Y, Hendricks JA, Ghosh B, Szantai-Kis DM, Reis SA, Shah JV, Mazitschek R. Monoalkoxy BODIPYs-A Fluorophore Class for Bioimaging. Bioconjug Chem 2014. PubMed
  • Lee DH, Acharya SS, Kwon M, Drane P, Guan Y, Adelmant G, Kalev P, Shah J, Pellman D, Marto JA, Chowdhury D. Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks. Mol Cell 2014. PubMed
  • Rodriguez-Bravo V, Maciejowski J, Corona J, Buch HK, Collin P, Kanemaki MT, Shah JV, Jallepalli PV. Nuclear pores protect genome integrity by assembling a premitotic and mad1-dependent anaphase inhibitor. Cell 2014; 156:1017-31. PubMed
  • Bodor DL, Mata JF, Sergeev M, David AF, Salimian KJ, Panchenko T, Cleveland DW, Black BE, Shah JV, Jansen LE. The quantitative architecture of centromeric chromatin. Elife 2014; 3:e02137. PubMed
  • Prentice-Mott HV, Chang CH, Mahadevan L, Mitchison TJ, Irimia D, Shah JV. Biased migration of confined neutrophil-like cells in asymmetric hydraulic environments. Proc Natl Acad Sci U S A 2013; 110:21006-11. PubMed
  • Jin X, Mohieldin AM, Muntean BS, Green JA, Shah JV, Mykytyn K, Nauli SM. Cilioplasm is a cellular compartment for calcium signaling in response to mechanical and chemical stimuli. Cell Mol Life Sci 2013. PubMed
  • Gaglia G, Guan Y, Shah JV, Lahav G. Activation and control of p53 tetramerization in individual living cells. Proc Natl Acad Sci U S A 2013; 110:15497-501. PubMed
  • Kops GJ, Shah JV. Connecting up and clearing out: how kinetochore attachment silences the spindle assembly checkpoint. Chromosoma 2012; 121:509-25. PubMed
  • Hartlerode AJ, Guan Y, Rajendran A, Ura K, Schotta G, Xie A, Shah JV, Scully R. Impact of histone H4 lysine 20 methylation on 53BP1 responses to chromosomal double strand breaks. PLoS ONE 2012; 7:e49211. PubMed
  • Shah JV. Cells in tight spaces: the role of cell shape in cell function. J Cell Biol 2010; 191:233-6. PubMed
  • Albrecht DR, Underhill GH, Resnikoff J, Mendelson A, Bhatia SN, Shah JV. Microfluidics-integrated time-lapse imaging for analysis of cellular dynamics. Integr Biol (Camb) 2010; 2:278-87. PubMed
  • Kops GJ, van der Voet M, Manak MS, van Osch MH, Naini SM, Brear A, McLeod IX, Hentschel DM, Yates JR, van den Heuvel S, Shah JV. APC16 is a conserved subunit of the anaphase-promoting complex/cyclosome. J Cell Sci 2010; 123:1623-33. PubMed
  • Kwiatkowski N, Jelluma N, Filippakopoulos P, Soundararajan M, Manak MS, Kwon M, Choi HG, Sim T, Deveraux QL, Rottmann S, Pellman D, Shah JV, Kops GJ, Knapp S, Gray NS. Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function. Nat Chem Biol 2010; 6:359-68. PubMed
  • Besschetnova TY, Kolpakova-Hart E, Guan Y, Zhou J, Olsen BR, Shah JV. Identification of signaling pathways regulating primary cilium length and flow-mediated adaptation. Curr Biol 2010; 20:182-7. PubMed
  • Hardwick KG, Shah JV. Spindle checkpoint silencing: ensuring rapid and concerted anaphase onset. F1000 Biol Rep 2010; 2:55. PubMed
  • Ciliberto A, Shah JV. A quantitative systems view of the spindle assembly checkpoint. EMBO J 2009; 28:2162-2173. PubMed
  • Besschetnova TY, Roy B, Shah JV. Imaging intraflagellar transport in mammalian primary cilia. Methods Cell Biol. 2010; 93:331-46. PubMed
  • Tran PV, Haycraft CJ, Besschetnova TY, Turbe-Doan A, Stottmann RW, Herron BJ, Chesebro AL, Qiu H, Scherz PJ, Shah JV, Yoder BK, Beier DR. THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nat Genet 2008; 40:403-10. PubMed
  • Sabath E, Negoro H, Beaudry S, Paniagua M, Angelow S, Shah J, Grammatikakis N, Yu AS, Denker BM. G{alpha}12 regulates protein interactions within the MDCK cell tight junction and inhibits tight-junction assembly. J Cell Sci 2008; 121:814-24. PubMed
  • Black BE, Jansen LE, Maddox PS, Foltz DR, Desai AB, Shah JV, Cleveland DW. Centromere identity maintained by nucleosomes assembled with histone H3 containing the CENP-A targeting domain. Mol Cell 2007; 25:309-22. PubMed
  • Wang Z, Shah JV, Berns MW, Cleveland DW. In vivo quantitative studies of dynamic intracellular processes using fluorescence correlation spectroscopy. Biophys J 2006; 91:343-51. PubMed
  • Bomont P, Maddox P, Shah JV, Desai AB, Cleveland DW. Unstable microtubule capture at kinetochores depleted of the centromere-associated protein CENP-F. EMBO J 2005; 24:3927-39. PubMed
  • Botvinick EL, Venugopalan V, Shah JV, Liaw LH, Berns MW. Controlled ablation of microtubules using a picosecond laser. Biophys J 2004; 87:4203-12. PubMed
  • Shah JV, Botvinick E, Bonday Z, Furnari F, Berns M, Cleveland DW. Dynamics of centromere and kinetochore proteins; implications for checkpoint signaling and silencing. Curr Biol 2004; 14:942-52. PubMed
  • Wang Z, Shah JV, Chen Z, Sun CH, Berns MW. Fluorescence correlation spectroscopy investigation of a GFP mutant-enhanced cyan fluorescent protein and its tubulin fusion in living cells with two-photon excitation. J Biomed Opt 2004; 9:395-403. PubMed
  • Shah JV, Cleveland DW. Slow axonal transport: fast motors in the slow lane. Curr Opin Cell Biol 2002; 14:58-62. PubMed
  • Tang JX, K. Counterion-induced actin ring formation. Eur Biophys J 2002; 30:477-84. PubMed
  • Janmey PA, Shah JV, Tang JX, Stossel TP. Actin filament networks. Results Probl Cell Differ 2000; 32:181-99. PubMed
  • Shah JV, Cleveland DW. Waiting for anaphase: Mad2 and the spindle assembly checkpoint. Cell 2001; 103:997-1000. PubMed
  • Shah JV, Flanagan LA, Janmey PA, Leterrier JF. Bidirectional translocation of neurofilaments along microtubules mediated in part by dynein/dynactin. Mol Biol Cell 2000; 11:3495-508. PubMed
  • Shah JV, Goldstein LS. Does motor protein intelligence contribute to neuronal polarity? Neuron 2000; 26:281-2. PubMed
  • Allen PG, Shah JV. Brains and brawn: plectin as regulator and reinforcer of the cytoskeleton. Bioessays 1999; 21:451-4. PubMed
  • Janmey PA, Kas J, Shah JV, Allen PG, Tang JX. Cytoskeletal networks and filament bundles: regulation by proteins and polycations. Biol Bull 2001; 194:334-5; discussion 335-6. PubMed
  • Shah JV, Wang LZ, Traub P, Janmey PA. Interaction of vimentin with actin and phospholipids. Biol Bull 1998; 194:402-5. PubMed
  • Poon CS, Shah JV. Hebbian learning in parallel and modular memories. Biol Cybern 1998; 78:79-86. PubMed
  • Janmey PA, Shah JV, Janssen KP, Schliwa M. Viscoelasticity of intermediate filament networks. Subcell Biochem 1999; 31:381-97. PubMed
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