Alan F. Horwitz

Education

  • PhD, Stanford University, Stanford, CA
  • BA, University of Wisconsin, Madison
  • Postdoc, University of California, Berkeley, CA

Primary Appointment

  • Professor, Cell Biology

Contact

Research Interest(s)

Synapse Formation and Cell Migration in Normal and Pathobiology-Adhesion, Signaling, Imaging and Proteomics

Research Description

Our major research goal is to elucidate the mechanisms that underlie directed cell migration from its initiation to its termination. This interest stems from the pivotal role of migration in a variety of normal and pathological processes extending from the development to the adult. During development, for example, cells migrate from their birthplaces to distant locations where they then differentiate. While this process is repeated throughout the embryo, it plays out spectacularly in the nervous system. Neuronal precursors migrate from their birthplaces to their final residences and then proceed to extend neuronal growth cones to their targets, where they form synaptic connections with appropriate target cells. In this context, it is no surprise that a large fraction of the congenital brain and heart defects arise from perturbed cell migration. Migration contributes to numerous pathological phenomena as well. It plays a pivotally role in the formation of tumors, which requires the invasion of vasculature as well as in metastasis, the spread of tumors from the primary tumor mass to distant sites where secondary tumors form. Migration also contributes to other disease processes including chronic inflammatory diseases, via leukocyte invasion and vascular disease via smooth muscle migration. Finally, migration participates centrally in normal tissue regeneration and wound repair.

Current research projects include: a) the assembly and disassembly of adhesions, b) the trafficking of adhesion components, c) characterizing the migration proteome d) developing in vivo systems for studying migration e) developing new imaging technologies for migration studies, and f) studying mechanisms of synapse formation and spine dynamics. While most of our studies utilize migrating fibroblasts and neuronal cells, we are interested in any aspect of migration and migration related phenomena - from embryonic development to cancer and regeneration.

Selected Publications

  • Chen L, Vicente-Manzanares M, Potvin-Trottier L, Wiseman P, Horwitz A. The integrin-ligand interaction regulates adhesion and migration through a molecular clutch. PloS one. 2012;7(7): e40202. PMID: 22792239 | PMCID: PMC3391238
  • Choi C, Zareno J, Digman M, Gratton E, Horwitz A. Cross-correlated fluctuation analysis reveals phosphorylation-regulated paxillin-FAK complexes in nascent adhesions. Biophysical journal. 2011;100(3): 583-92. PMID: 21281572 | PMCID: PMC3030238
  • Hodges J, Newell-Litwa K, Asmussen H, Vicente-Manzanares M, Horwitz A. Myosin IIb activity and phosphorylation status determines dendritic spine and post-synaptic density morphology. PloS one. 2011;6(8): e24149. PMID: 21887379 | PMCID: PMC3162601
  • Newell-Litwa K, Horwitz A. Cell migration: PKA and RhoA set the pace. Current biology : CB. 2011;21(15): R596-8. PMID: 21820627
  • Vicente-Manzanares M, Newell-Litwa K, Bachir A, Whitmore L, Horwitz A. Myosin IIA/IIB restrict adhesive and protrusive signaling to generate front-back polarity in migrating cells. The Journal of cell biology. 2011;193(2): 381-96. PMID: 21482721 | PMCID: PMC3080254
  • Parsons J, Horwitz A, Schwartz M. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nature reviews. Molecular cell biology. 2010;11(9): 633-43. PMID: 20729930 | PMCID: PMC2992881
  • Vicente-Manzanares M, Horwitz A. Myosin light chain mono- and di-phosphorylation differentially regulate adhesion and polarity in migrating cells. Biochemical and biophysical research communications. 2010;402(3): 537-42. PMID: 20971064 | PMCID: PMC2991406
  • The matrix revolutions. Nature reviews. Molecular cell biology. 2009;10(10): 653. PMID: 19780224
  • Choi C, Vicente-Manzanares M, Zareno J, Whitmore L, Mogilner A, Horwitz A. Actin and alpha-actinin orchestrate the assembly and maturation of nascent adhesions in a myosin II motor-independent manner. Nature cell biology. 2009;10(9): 1039-50. PMID: 19160484 | PMCID: PMC2827253
  • Vicente-Manzanares M, Choi C, Horwitz A. Integrins in cell migration--the actin connection. Journal of cell science. 2009;122 199-206. PMID: 19118212 | PMCID: PMC2714416
  • Vicente-Manzanares M, Ma X, Adelstein R, Horwitz A. Non-muscle myosin II takes centre stage in cell adhesion and migration. Nature reviews. Molecular cell biology. 2009;10(11): 778-90. PMID: 19851336 | PMCID: PMC2834236
  • Brown C, Dalal R, Hebert B, Digman M, Horwitz A, Gratton E. Raster image correlation spectroscopy (RICS) for measuring fast protein dynamics and concentrations with a commercial laser scanning confocal microscope. Journal of microscopy. 2008;229 78-91. PMID: 18173647
  • Digman M, Brown C, Horwitz A, Mantulin W, Gratton E. Paxillin dynamics measured during adhesion assembly and disassembly by correlation spectroscopy. Biophysical journal. 2007;94(7): 2819-31. PMID: 17993500 | PMCID: PMC2267137
  • Huttenlocher A, Horwitz A. Wound healing with electric potential. The New England journal of medicine. 2007;356(3): 303-4. PMID: 17229960
  • Brown C, Hebert B, Kolin D, Zareno J, Whitmore L, Horwitz A, Wiseman P. Probing the integrin-actin linkage using high-resolution protein velocity mapping. Journal of cell science. 2006;119 5204-14. PMID: 17158922
  • Nayal A, Webb D, Brown C, Schaefer E, Vicente-Manzanares M, Horwitz A. Paxillin phosphorylation at Ser273 localizes a GIT1-PIX-PAK complex and regulates adhesion and protrusion dynamics. The Journal of cell biology. 2006;173(4): 587-9. PMID: 16717130 | PMCID: PMC2063867