Denise Carol Hocking, Ph.D.

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Research in the Hocking lab focuses on understanding the mechanisms by which the extracellular matrix protein, fibronectin, affects cell and tissue functions that are critical for wound repair. We study both the structural mechanisms and intracellular signaling events that mediate cell and tissue responses to matrix fibronectin. In turn, we are using this information to develop novel technologies for tissue engineering, and therapeutic approaches to promote tissue regeneration in chronic wounds.

The Extracellular Matrix: What is it? The extracellular matrix (ECM) is a complex, three-dimensional network comprised of collagens, glycoproteins, and proteoglycans that provides an adhesive substrate for the organization of cells into tissues. In the adult, dynamic interactions between cells and their surrounding ECM proteins regulate most, if not all, cell and tissue functions. ECM proteins also contribute to the mechanical and permeability properties of the skin, vasculature, lungs, and other organs. Fibronectin is a principal component of the ECM, where it is organized into elongated, branching fibrils. Mechanical forces influence the deposition, organization, and structure of ECM fibronectin fibrils, which in turn, affect cell function, ECM organization and stability, vascular perfusion, blood vessel permeability, and tissue strength. Fibronectin is initially secreted by cells in a soluble, protomeric form. Soluble fibronectins are then polymerized into ECM fibrils by means of a tightly-regulated, cell-dependent mechanism that can be rapidly up- or down-regulated. Fibronectin matrix polymerization is increased in response to tissue injury; altered fibronectin matrix deposition is associated with abnormal tissue repair in a number of chronic inflammatory states, including non-healing wounds, asthma, pulmonary fibrosis, and atherosclerosis. In the body, fibronectin polymerization is a continuous process, with as much as 50% of the fibronectin matrix undergoing turnover every 24 hours. In spite of this remarkable information, the mechanisms of fibronectin matrix polymerization and the function of ECM fibronectin fibrils in vivo is not well understood.

Studies from the Hocking Lab: What have we learned about fibronectin? Research in the Hocking lab has been directed at determining whether and how this three-dimensional fibronectin matrix regulates cell behaviors that are essential to tissue repair. Our studies have firmly established that cells respond differently to soluble versus ECM fibronectin, and that the ECM form is the primary functional form of fibronectin. We have shown that the conversion of fibronectin into the ECM form specifically stimulates cell spreading, cell migration, and collagen matrix contraction – all cellular events critical to tissue regeneration. We have also shown that the assembly of a fibronectin matrix promotes the co-polymerization of collagen I and enhances the tensile strength of model tissue, thus demonstrating that the organization and functional properties of the ECM are also dependent on fibronectin matrix polymerization. We have localized several of the ECM-specific effects of fibronectin to a single, cryptic heparin-binding site in the first type III module of fibronectin (FNIII-1). This conformation-dependent, or "matricryptic" site is not exposed in soluble fibronectin, but becomes unmasked during fibronectin matrix formation or as cells and tissues exert tension on ECM fibronectin fibrils. Our exciting new studies, conducted in collaboration with the laboratory of Dr. Ingrid Sarelius, demonstrate that exposure of this matricryptic site in vivo mechanically couples skeletal muscle contraction with local vasodilation. These were the first studies to demonstrate a role for fibronectin fibrils in adult connective tissue in vivo.

Current Appointments

• Associate Professor - Department of Pharmacology and Physiology (SMD)

Education
PhD Physiology	Albany Medical College	1992
MS Physiology	Albany Medical College	1990
BS Medical Technology	Hartwick College	1983

Post-Doctoral Training & Residency
Postdoctoral Research Fellow; Albany Medical College, Albany, NY. Topic: "Mechanisms of extracellular matrix fibronectin deposition". Advisor: Paula J. McKeown-Longo, Ph.D.	1992 - 1996

Fellowship Awards
Henry Schaffer Biomedical Science Fellowship Award; Albany Medical College, Albany, NY. "Mechanisms and Consequences of Fibronectin Matrix Deposition.	1996 - 1998
American Heart Association Postdoctoral Fellowship #950210, New York State Affiliate, "Regulation of Fibronectin Polymerization by Cells".	1995 - 1996
NIH Institutional Postdoctoral Fellowship, Dept. of Physiology and Cell Biology, Albany Medical College, Albany, NY.	1992 - 1995
NIH Institutional Predoctoral Fellowship, Dept. of Physiology and Cell Biology, Albany Medical College, Albany, NY.	1988 - 1991

Lab Website

http://www.urmc.rochester.edu/phph/projects/hocking/

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Recent Journal Articles
Showing the 5 most recent journal articles. (20 available)
Hocking DC; Titus PA; Sumagin R; Sarelius IH. "Extracellular matrix fibronectin mechanically couples skeletal muscle contraction with local vasodilation." Circulation research. 2008; 102(3):372-9. Epub 2007 Nov 21.
Gui L; Wojciechowski K; Gildner CD; Nedelkovska H; Hocking DC. "Identification of the heparin-binding determinants within fibronectin repeat III1: role in cell spreading and growth." The Journal of biological chemistry. 2006; 281(46):34816-25. Epub 2006 Sep 18.
Gildner CD; Lerner AL; Hocking DC. "Fibronectin matrix polymerization increases tensile strength of model tissue." American journal of physiology. Heart and circulatory physiology. 2004; 287(1):H46-53. Epub 2004 Mar 04.
Wojciechowski K; Chang CH; Hocking DC. "Expression, production, and characterization of full-length vitronectin in Escherichia coli." Protein expression and purification. 2004; 36(1):131-8.
Hocking DC; Chang CH. "Fibronectin matrix polymerization regulates small airway epithelial cell migration." American journal of physiology. Lung cellular and molecular physiology. 2003; 285(1):L169-79. Epub 2003 Mar 14.