Derek K. Toomre, Ph.D

Associate Professor of Cell Biology Director of Yale CINEMA Lab Cellular mechanisms that regulate the dynamics of vesicle tethering, docking and fusion and related role in cancer and diabetes.
Phone: (203) 785-4319 Lab: (203) 785-5057 CINEMA Lab: (203) 785-7371 Fax: (203) 785-3559 e-mail: derek.toomre@yale.edu		Department of Cell Biology Yale University School of Medicine 333 Cedar Street PO Box 208002 New Haven, CT 06520-8002 <Courier Address> 333 Cedar Street, SHM C-227 (Lab: SHM C-229) New Haven, CT 06510-3206

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A major focus of our lab is on the spatial-temporal control of exo-endocytosis and the cellular and molecular mechanisms that regulate it. We are studying constitutive and regulated secretion in a variety of cellular processes including: i) insulin-stimulated secretion of Glut4 vesicles, ii) cytokinesis, and iii) cell migration with the long-term aim of helping understand the pathology of diabetes and cancer. A major emphasis is on the spatial-temporal regulation of vesicle tethering, docking and fusion using live 3D imaging of single vesicles and even single molecules. Cellular machinery of particular interest are the exocyst complex, GTPases, and microtubules.

To achieve these goals we develop and exploit state-of-the-art live cell microscopy with quantitative image analysis and modeling, genetic manipulation (RNAi) and complementary biochemical assays. Live cell imaging is realized in the Yale CINEMA Lab which is under my directorship and utilizes novel multi-angle TIRF microscopy (patents pending), spinning-disk confocal microscopy and super-resolution microscopy.

Figure 1: New Views and Insights with Fluorescent Imaging of Cells and Tissue.
Top left: Complex structural organization of tissue as seen in from section of human colon using A33, an antibody developed by the LICR and further characterized here.
Top Right: Multispectral imaging of a cell with markers for the nucleus (blue), clustered lipid raft marker (green) and actin (red).
Bottom left: Red tracks of vesicles as they move along microtubules (green) in living cells (see Toomre et al, 1999 [PDF] ).
Bottom right: High resolution view of a single vesicle (only ~100 nanometers across) fusing with the cell surface, using a specialized TIRFM imaging. The time-lapse series is shown in 1 second intervals (left-to-right) and when the vesicle fuses an enormous flash is seen (see Toomre et eal., 2000 [PDF]).

Link: The CINEMA Lab "Cinema Imaging Using New Microscopy Approaches"

Press Releases

The Endocytic Ballet of Traffic and Signalling

NIH New Innovator Award Support of New Microscopy
Yale News NIH New Innovator Award

Selected Publications

Letinic K, Sebastian R, Toomre D, Rakic P. Exocyst is involved in polarized
cell migration and cerebral cortical development. Proc Natl Acad Sci U S A. 2009
Jul 7;106(27):11342-7.

Zoncu R, Perera RM, Balkin DM, Pirruccello M, Toomre D, De Camilli P. A
phosphoinositide switch controls the maturation and signaling properties of APPL
endosomes. Cell. 2009 Mar 20;136(6):1110-21.

Goss JW, Toomre DK. Both daughter cells traffic and exocytose membrane at the
cleavage furrow during mammalian cytokinesis. J Cell Biol. 2008 181(7):1047-54.

Krylyshkina O, Anderson KI, Kaverina I, Upmann I, Manstein DJ, Small JV, Toomre DK. Nanometer targeting of microtubules to focal adhesions. J. Cell Biol. 161(5): 853-9, 2003.

Toomre D, Steyer JA, Keller P, Almers W, Simons K. Fusion of constitutive
membrane traffic with the cell surface observed by evanescent wave microscopy. J
Cell Biol. 2000 Apr 3;149(1):33-40.

Toomre D, Manstein DJ. Lighting up the cell surface with evanescent wave microscopy. Trends Cell Biol. 2001.

Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9.

Toomre, D.*, Keller, P.*, White, J., Olivo, J.C., and Simons, K. Dual-color visualization of trans-Golgi network to plasma membrane traffic along microtubules in living cells. J. Cell Sci. 112: 21-33, 1999.