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.
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• 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.
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