Alan K. Howe, Ph.D.
Assistant Professor, Department of Pharmacology
Vermont
Cancer Center
University
of Vermont College of Medicine
Burlington, VT 05405
Ph: (802) 656-9521
Fax: (802) 656-8788
The growth and development of cells into tissues and organs, and the maintenance
of tissue and organ health, is completely dependent on the successful integration
of signals arising from soluble factors and positional and morphological signals
arising from cell adhesion to extracellular matrix (ECM). An archetypal example
of this regulation is the phenomenon of anchorage-dependent growth, a fundamental
characteristic of most normal cells whereby proliferation is restricted and
survival compromised in the absence of adhesion to an appropriate ECM. Subversion
of normal adhesion-regulated signaling mechanisms directly contributes to the
uncontrolled growth and aggressive migration of malignant tumor cells.
Research in my laboratory focuses on understanding how cell adhesion to ECM regulates and specifies the signal transduction processes leading to cell movement and cell division. Specifically, we study the cAMP-dependent protein kinase (or PKA), how it is regulated by cell adhesion, and how it contributes to regulation of the actin cytoskeleton. The laboratory uses a combination of biochemical techniques and multi-dimensional microscopy to analyze the subcellular distribution and spatial regulation of PKA, its upstream regulators, and its downstream targets involved in cytoskeletal organization. The lab also has burgeoning interests in the identification & characterization of changes in protein phosphorylation on a proteome-wide scale (phosphoproteomics), and the development of experimentally tractable cell culture systems for modeling metastasis and analyzing adhesion-related signaling events during metastatic cell migration.
Click here for a more detailed description, including a few figures.
Select Publications
Deming PB, Campbell SL, Baldor LC, and Howe AK. Protein Kinase A regulates 3' phosphatidylinositide dynamics during PDGF-induced membrane ruffling and chemotaxis. J. Biol. Chem. (in press)
Phalen TJ, Weirather K, Deming PB, Anathy V, Howe AK, van der Vliet A, Jonsson T, Poole L, and Heintz NH. Hyper-oxidation governs structural transitions in peroxiredoxin II oligomers that correlate with cell cycle arrest and recovery. J. Cell Biol. 2006. 175:779-789 (cover article).
Langevin HM, Bouffard NA, Badger GJ, Churchill DL, Howe AK. 2006. Subcutaneous tissue fibroblast cytoskeletal remodeling induced by acupuncture: Evidence for a mechanotransduction-based mechanism. J. Cell Physiol. 2006. 207:767-774.
Langevin HM, Bouffard NA, Badger GJ, Iatridis JC, and Howe AK. 2005 Dynamic fibroblast cytoskeletal response to subcutaneous tissue stretch ex vivo and in vivo. Am. J. Physiol. Cell Physiol. 2005. 288:C747-756.
Howe AK, Baldor LC, and Hogan BP. Spatial regulation of cAMP-dependent protein kinase during chemotaxis. Proc. Natl. Acad. Sci. USA 2005. 104:14320-14325.
Howe AK. 2004. Regulation of actin-based cell migration by cAMP and PKA (Review). Biochim. Biophys. Acta 2004. 1692:159-174.
Goldfinger LE, Han J, Kiosses WB, Howe AK, and Ginsberg MH. Spatial restriction of alpha4-integrin phosphorylation regulates lamellipodial stability and alpha4 beta1-dependent cell migration. J. Cell. Biol. 2003. 162:731-741.
Howe AK, Hogan BP, Juliano RL. Regulation of vasodilator-stimulated phosphoprotein phosphorylation and interaction with Abl by protein kinase A and cell adhesion. J. Biol. Chem. 2002. 277: 38121-38126
Howe AK. Cell adhesion regulates the interaction between Nck and p21-activated kinase. J. Biol. Chem. 2001. 276:14541-14544.
Edin M, Howe AK, Juliano RL. Inhibition of PKA negatively regulates fibroblast motility. Exp. Cell Res. 2001. 270:214-222.
Howe AK, Juliano RL. Regulation of anchorage-dependent signal transduction by protein kinase A and p21-activated kinase. Nature Cell Biol. 2000. 2:593-600.
Howe A, Aplin AE, Alahari S, Juliano RL. Integrin signaling and cell growth
control. Curr. Opin. Cell Biol. 1998. 10:220-231.
Dr. Howe's CV (NIH Biosketch)
Last modified October 22 2008 01:18 PM
