Adhesion, Migration, Cytoskeleton

Focal adhesions and related adherens-type junctions are tightly associated with the actin cytoskeleton and display a complex interplay between them. Both are mechanosensitive structures, and play key roles in maintaining tissue integrity and functionality. Work conducted in the Geiger laboratory addressed diverse biological principles related to the environmental sensing properties of matrix adhesions (like focal adhesions) and cell-cell adhesions (tight junctions (see images below) and adherens-type junctions). Topics addressed in the laboratory over the years include (Key Recent Publications).

  • Characterization of the cadherin family of cell-cell adhesions
  • Relationships of tight junctions and adherens-type junctions
  • Negative interplay between cell-matrix and cell-cell adhesions (image 2)
  • Roles of microfilaments and microtubules in regulating adhesive interactions
  • Barrier function in the intestinal epithelium
  • Adhesive interactions of cancer cells

Perturbation of tight junctions by environmental perturbations

 

3-Dimensional organization of matrix adhesions (basal and apical cell-cell adhesions)

 

Key collaborations: Werner Franke, Sasha Bershasky, Avri Ben-Ze’ev, Eran Elinav,

Selected Publications

  1. Grosheva I., Zheng D., Levy M., Polansky O., Lichtenstein A., Golani O., Dori-Bachash M., Moresi C., Shapiro H., Del Mare-Roumani S., Valdes-Mas R., He Y., Karbi H., Chen M., Hermalin A., Straussman D., Yissachar N., Elinav E., Geiger B. High-Throughput Screen Identifies Host and Microbiota Regulators of Intestinal Barrier Function. Gastroenterology, S0016-5085(20)34921-0 (2020)
  2. Thaiss C.A, Levy M, Grosheva I, Zheng D, Soffer E, Blacher E, Braverman S, Zengeler A.C, Barak O, Elazar M, Ben-Zeev R, Lehavi-Regev D, Katz M.N, Pevsner-Fischer M, Gertler A, Halpern Z, Harmelin A, Aamar A, Serradas P, Grosfeld A, Shapiro H, Geiger B, Elinav E. Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection. Science 359(6382):1376-1383 (2018)
  3. Small JV, Geiger B, Kaverina I and Bershadsky A. Microtubules guide migrating cells by modulating adhesion site dynamics. Nature Rev Mol Cell Biol. 3(12): 957-64 (2002)
  4. Sadot E, Conacci-Sorrell M, Zhurinsky J, Shnizer D, Lando Z, Zharhary D, Kam Z, Ben-Ze'ev A and Geiger B. Regulation of S33/S37 phosphorylated beta-catenin in normal and transformed cells. J Cell Sci. 115(Pt 13): 2771-80 (2002).
  5. Geiger B, Bershadsky A, Pankov R and Yamada K. Transmembrane crosstalk between the extracellular  matrix-cytoskeleton. Nature Rev Mol Cell Biol. 2(11): 793-805 (2001)
  6. Sadot E, Simcha I, Iwai K, Ciechanover A, Geiger B and Ben-Ze’ev A. Differential interaction of plakoglobin and beta-catenin with the ubiquitin-proteasome system. Oncogene 19(16): 1992-2001 (2000)
  7. Katz B-Z, Zamir E, Bershadsky A, Kam Z, Yamada KM and Geiger B.  Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions. Mol Biol Cell 11: 1047-60 (2000)