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Denise Hocking

TitleAssociate Professor
InstitutionSchool of Medicine and Dentistry
DepartmentPharmacology and Physiology
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 711
Rochester NY 14642
Other Positions
TitleAssociate Professor
InstitutionSchool of Medicine and Dentistry
DepartmentBiomedical Engineering

 
 Awards And Honors
1990     Proctor and Gamble Career Opportunity Award, American Physiological Society.
 
 Overview
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.

 
 Selected Publications
List All   |   Timeline
  1. Sevilla CA, Dalecki D, Hocking DC. Regional fibronectin and collagen fibril co-assembly directs cell proliferation and microtissue morphology. PLoS One. 2013; 8(10):e77316.
    View in: PubMed
  2. Roy DC, Mooney NA, Raeman CH, Dalecki D, Hocking DC. Fibronectin matrix mimetics promote full-thickness wound repair in diabetic mice. Tissue Eng Part A. 2013 Nov; 19(21-22):2517-26.
    View in: PubMed
  3. Garvin KA, Dalecki D, Yousefhussien M, Helguera M, Hocking DC. Spatial patterning of endothelial cells and vascular network formation using ultrasound standing wave fields. J Acoust Soc Am. 2013 Aug; 134(2):1483-90.
    View in: PubMed
  4. Garvin KA, Vanderburgh J, Hocking DC, Dalecki D. Controlling collagen fiber microstructure in three-dimensional hydrogels using ultrasound. J Acoust Soc Am. 2013 Aug; 134(2):1491-502.
    View in: PubMed
  5. Roy DC, Hocking DC. Recombinant fibronectin matrix mimetics specify integrin adhesion and extracellular matrix assembly. Tissue Eng Part A. 2013 Feb; 19(3-4):558-70.
    View in: PubMed
  6. Garvin KA, Dalecki D, Hocking DC. Vascularization of three-dimensional collagen hydrogels using ultrasound standing wave fields. Ultrasound Med Biol. 2011 Nov; 37(11):1853-64.
    View in: PubMed
  7. Roy DC, Wilke-Mounts SJ, Hocking DC. Chimeric fibronectin matrix mimetic as a functional growth- and migration-promoting adhesive substrate. Biomaterials. 2011 Mar; 32(8):2077-87.
    View in: PubMed
  8. Lefort CT, Wojciechowski K, Hocking DC. N-cadherin cell-cell adhesion complexes are regulated by fibronectin matrix assembly. J Biol Chem. 2011 Jan 28; 286(4):3149-60.
    View in: PubMed
  9. Garvin KA, Hocking DC, Dalecki D. Controlling the spatial organization of cells and extracellular matrix proteins in engineered tissues using ultrasound standing wave fields. Ultrasound Med Biol. 2010 Nov; 36(11):1919-32.
    View in: PubMed
  10. Sevilla CA, Dalecki D, Hocking DC. Extracellular matrix fibronectin stimulates the self-assembly of microtissues on native collagen gels. Tissue Eng Part A. 2010 Dec; 16(12):3805-19.
    View in: PubMed
  11. Hocking DC, Titus PA, Sumagin R, Sarelius IH. Extracellular matrix fibronectin mechanically couples skeletal muscle contraction with local vasodilation. Circ Res. 2008 Feb 15; 102(3):372-9.
    View in: PubMed
  12. 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. J Biol Chem. 2006 Nov 17; 281(46):34816-25.
    View in: PubMed
  13. Wojciechowski K, Chang CH, Hocking DC. Expression, production, and characterization of full-length vitronectin in Escherichia coli. Protein Expr Purif. 2004 Jul; 36(1):131-8.
    View in: PubMed
  14. Gildner CD, Lerner AL, Hocking DC. Fibronectin matrix polymerization increases tensile strength of model tissue. Am J Physiol Heart Circ Physiol. 2004 Jul; 287(1):H46-53.
    View in: PubMed
  15. Hocking DC, Chang CH. Fibronectin matrix polymerization regulates small airway epithelial cell migration. Am J Physiol Lung Cell Mol Physiol. 2003 Jul; 285(1):L169-79.
    View in: PubMed
  16. Hocking DC. Fibronectin matrix deposition and cell contractility: implications for airway remodeling in asthma. Chest. 2002 Dec; 122(6 Suppl):275S-278S.
    View in: PubMed
  17. Sottile J, Hocking DC. Fibronectin polymerization regulates the composition and stability of extracellular matrix fibrils and cell-matrix adhesions. Mol Biol Cell. 2002 Oct; 13(10):3546-59.
    View in: PubMed
  18. Hocking DC, Kowalski K. A cryptic fragment from fibronectin's III1 module localizes to lipid rafts and stimulates cell growth and contractility. J Cell Biol. 2002 Jul 8; 158(1):175-84.
    View in: PubMed
  19. Pereira M, Rybarczyk BJ, Odrljin TM, Hocking DC, Sottile J, Simpson-Haidaris PJ. The incorporation of fibrinogen into extracellular matrix is dependent on active assembly of a fibronectin matrix. J Cell Sci. 2002 Feb 1; 115(Pt 3):609-17.
    View in: PubMed
  20. Sottile J, Hocking DC, Langenbach KJ. Fibronectin polymerization stimulates cell growth by RGD-dependent and -independent mechanisms. J Cell Sci. 2000 Dec; 113 Pt 23:4287-99.
    View in: PubMed
  21. Hocking DC, Sottile J, Langenbach KJ. Stimulation of integrin-mediated cell contractility by fibronectin polymerization. J Biol Chem. 2000 Apr 7; 275(14):10673-82.
    View in: PubMed
  22. Hocking DC, Sottile J, Reho T, Fässler R, McKeown-Longo PJ. Inhibition of fibronectin matrix assembly by the heparin-binding domain of vitronectin. J Biol Chem. 1999 Sep 17; 274(38):27257-64.
    View in: PubMed
  23. Sottile J, Hocking DC, Swiatek PJ. Fibronectin matrix assembly enhances adhesion-dependent cell growth. J Cell Sci. 1998 Oct; 111 ( Pt 19):2933-43.
    View in: PubMed
  24. Hocking DC, Sottile J, McKeown-Longo PJ. Activation of distinct alpha5beta1-mediated signaling pathways by fibronectin's cell adhesion and matrix assembly domains. J Cell Biol. 1998 Apr 6; 141(1):241-53.
    View in: PubMed
  25. Hocking DC, Smith RK, McKeown-Longo PJ. A novel role for the integrin-binding III-10 module in fibronectin matrix assembly. J Cell Biol. 1996 Apr; 133(2):431-44.
    View in: PubMed
  26. Hocking DC, Sottile J, McKeown-Longo PJ. Fibronectin's III-1 module contains a conformation-dependent binding site for the amino-terminal region of fibronectin. J Biol Chem. 1994 Jul 22; 269(29):19183-7.
    View in: PubMed
  27. Ferro TJ, Hocking DC, Johnson A. Tumor necrosis factor-alpha alters pulmonary vasoreactivity via neutrophil-derived oxidants. Am J Physiol. 1993 Nov; 265(5 Pt 1):L462-71.
    View in: PubMed
  28. Webb E, Tkalcevic J, Edwards S, Hocking D, Nisbet I. Expression of biologically active human factor VIII using a baculovirus vector. Biochem Biophys Res Commun. 1993 Jan 29; 190(2):536-43.
    View in: PubMed
  29. Hocking D, Ferro TJ, Johnson A. Dextran sulfate and heparin sulfate inhibit platelet-activating factor-induced pulmonary edema. J Appl Physiol. 1992 Jan; 72(1):179-85.
    View in: PubMed
  30. Johnson A, Hocking DC, Ferro TJ. Tumor necrosis factor-alpha primes pulmonary hemodynamic response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine. Am J Physiol. 1991 Oct; 261(4 Pt 2):H996-1004.
    View in: PubMed
  31. Hocking DC, Ferro TJ, Johnson A. Dextran sulfate inhibits PMN-dependent hydrostatic pulmonary edema induced by tumor necrosis factor. J Appl Physiol. 1991 Mar; 70(3):1121-8.
    View in: PubMed
  32. Hocking DC, Phillips PG, Ferro TJ, Johnson A. Mechanisms of pulmonary edema induced by tumor necrosis factor-alpha. Circ Res. 1990 Jul; 67(1):68-77.
    View in: PubMed
  33. Johnson A, Hocking DC, Ferro TJ. Mechanisms of pulmonary edema induced by a diacylglycerol second messenger. Am J Physiol. 1990 Jan; 258(1 Pt 2):H85-91.
    View in: PubMed
  34. Johnson A, Phillips P, Hocking D, Tsan MF, Ferro T. Protein kinase inhibitor prevents pulmonary edema in response to H2O2. Am J Physiol. 1989 Apr; 256(4 Pt 2):H1012-22.
    View in: PubMed

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