DF/HCC Program Affiliation

Cancer Cell Biology
Kidney Cancer

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

• Wang Z, Shah JV, Berns MW, Cleveland DW.In vivo quantitative studies of dynamic intracellular processes using fluorescence correlation spectroscopy.Biophys J 2006 Jul 1;91(1):343-51.
  16603490
• 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 Nov 16;24(22):3927-39.
  16252009
• Botvinick EL, Venugopalan V, Shah JV, Liaw LH, Berns MW.Controlled ablation of microtubules using a picosecond laser.Biophys J 2004 Dec;87(6):4203-12.
  15454403
• 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 Jun 8;14(11):942-52.
  15182667
• Shah JV, Cleveland DW.Waiting for anaphase: Mad2 and the spindle assembly checkpoint.Cell 2000 Dec 22;103(7):997-1000.
  11163175
• 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
  18327258
• 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 Mar 15;121(Pt 6):814-24.
  18285450
• 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 Jan 26;25(2):309-22.
  17244537
• 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 Mar-Apr;9(2):395-403.
  15065907
• Tang JX, Käs JA, Shah JV, Janmey PA.Counterion-induced actin ring formation.Eur Biophys J 2001 Dec;30(7):477-84.
  11820391
• Shah JV, Cleveland DW.Slow axonal transport: fast motors in the slow lane.Curr Opin Cell Biol 2002 Feb;14(1):58-62.
  11792545
• Janmey PA, Kas J, Shah JV, Allen PG, Tang JX.Cytoskeletal networks and filament bundles: regulation by proteins and polycations.Biol Bull 1998 Jun;194(3):334-5; discussion 335-6.
  11536877
• Janmey PA, Shah JV, Tang JX, Stossel TP.Actin filament networks.Results Probl Cell Differ 2001;32:181-99.
  11131831
• Shah JV, Flanagan LA, Janmey PA, Leterrier JF.Bidirectional translocation of neurofilaments along microtubules mediated in part by dynein/dynactin.Mol Biol Cell 2000 Oct;11(10):3495-508.
  11029051
• Shah JV, Goldstein LS.Does motor protein intelligence contribute to neuronal polarity?.Neuron 2000 May;26(2):281-2.
  10839344
• Allen PG, Shah JV.Brains and brawn: plectin as regulator and reinforcer of the cytoskeleton.Bioessays 1999 Jun;21(6):451-4.
  10402951
• Janmey PA, Shah JV, Janssen KP, Schliwa M.Viscoelasticity of intermediate filament networks.Subcell Biochem 1998;31:381-97.
  9932499
• Shah JV, Wang LZ, Traub P, Janmey PA.Interaction of vimentin with actin and phospholipids.Biol Bull 1998 Jun;194(3):402-5.
  9664674
• Poon CS, Shah JV.Hebbian learning in parallel and modular memories.Biol Cybern 1998 Feb;78(2):79-86.
  9525034