Jay W. Fox

Education

  • BA, Monmouth College, Monmouth, IL
  • PhD, Colorado State University, Ft. Collins, CO
  • Postdoc, University of CO Med. School, Denver, CO

Primary Appointment

  • Professor, Microbiology, Immunology, and Cancer Biology

Contact

Research Interest(s)

Basement Membrane Structure and Metalloproteinases

Research Description

My laboratory, in collaboration with my colleague Dr. Jon Bjarnason, was one of the first to identify and characterize the metalloproteinases present in numerous snake venoms. These Snake Venom Metalloproteinases; SVMPs are responsible for many of the pathologies associated with snake envenoming. Our research has elucidated the structures of these toxins and identified the biochemical and cellular mechanisms by which the toxins function to give rise to their noted pathologies. Specifically my research interests have been centered on metalloproteinases and extracellular matrix and the processes they regulate in normal and pathological circumstances. Our recent focus has expanded to include the interaction of host and tumor in carcinogenesis and metastasis and the role of stromal microenvironment, inflammation in cancer metastasis and invasion. We are also carrying out research on the discovery and validation of biomarkers associated with normal and chronic wound healing. Our longstanding interest in snake venom toxinology continues with studies aimed at elucidating novel molecular mechanisms associated with venom induced wound morbidity. We also are working on the identification of novel therapeutics from natural product libraries.

Selected Publications

  • Aramadhaka L, Prorock A, Dragulev B, Bao Y, Fox J. Connectivity maps for biosimilar drug discovery in venoms: the case of Gila monster venom and the anti-diabetes drug Byetta®. Toxicon : official journal of the International Society on Toxinology. 2013;69 160-7. PMID: 23602926
  • Mikesh L, Aramadhaka L, Moskaluk C, Zigrino P, Mauch C, Fox J. Proteomic anatomy of human skin. Journal of proteomics. 2013;84 190-200. PMID: 23563204
  • Abety A, Fox J, Schönefuss A, Zamek J, Landsberg J, Krieg T, Blobel C, Mauch C, Zigrino P. Stromal fibroblast-specific expression of ADAM-9 modulates proliferation and apoptosis in melanoma cells in vitro and in vivo. The Journal of investigative dermatology. 2012;132(10): 2451-8. PMID: 22622419
  • Aragão A, Belloni M, Simabuco F, Zanetti M, Yokoo S, Domingues R, Kawahara R, Pauletti B, Gonçalves A, Agostini M, Graner E, Coletta R, Fox J, Leme A. Novel processed form of syndecan-1 shed from SCC-9 cells plays a role in cell migration. PloS one. 2012;7(8): e43521. PMID: 22905270
  • Grigera P, Ma L, Borgman C, Pinto A, Sherman N, Parsons J, Fox J. Mass spectrometric analysis identifies a cortactin-RCC2/TD60 interaction in mitotic cells. Journal of proteomics. 2012;75(7): 2153-9. PMID: 22282019 | PMCID: PMC3312979
  • Tilghman R, Blais E, Cowan C, Sherman N, Grigera P, Jeffery E, Fox J, Blackman B, Tschumperlin D, Papin J, Parsons J. Matrix rigidity regulates cancer cell growth by modulating cellular metabolism and protein synthesis. PloS one. 2012;7(5): e37231. PMID: 22623999 | PMCID: PMC3356407
  • Escalante T, Ortiz N, Rucavado A, Sanchez E, Richardson M, Fox J, Gutiérrez J. Role of collagens and perlecan in microvascular stability: exploring the mechanism of capillary vessel damage by snake venom metalloproteinases. PloS one. 2011;6(12): e28017. PMID: 22174764
  • Kim J, Sherman N, Fox J, Ginsberg M. Phosphorylation sites in the cerebral cavernous malformations complex. Journal of cell science. 2011;124 3929-32. PMID: 22194303 | PMCID: PMC3244978
  • Rucavado A, Escalante T, Shannon J, Ayala-Castro C, Villalta M, Gutiérrez J, Fox J. Efficacy of IgG and F(ab')2 antivenoms to neutralize snake venom-induced local tissue damage as assessed by the proteomic analysis of wound exudate. Journal of proteome research. 2011;11(1): 292-305. PMID: 22004524
  • Rucavado A, Escalante T, Shannon J, Gutiérrez J, Fox J. Proteomics of wound exudate in snake venom-induced pathology: search for biomarkers to assess tissue damage and therapeutic success. Journal of proteome research. 2011;10(4): 1987-2005. PMID: 21306181
  • Eming S, Koch M, Krieger A, Brachvogel B, Kreft S, Bruckner-Tuderman L, Krieg T, Shannon J, Fox J. Differential proteomic analysis distinguishes tissue repair biomarker signatures in wound exudates obtained from normal healing and chronic wounds. Journal of proteome research. 2010;9(9): 4758-66. PMID: 20666496
  • Mauch C, Zamek J, Abety A, Grimberg G, Fox J, Zigrino P. Accelerated wound repair in ADAM-9 knockout animals. The Journal of investigative dermatology. 2010;130(8): 2120-30. PMID: 20376065
  • Paes Leme A, Escalante T, Pereira J, Oliveira A, Sanchez E, Gutiérrez J, Serrano S, Fox J. High resolution analysis of snake venom metalloproteinase (SVMP) peptide bond cleavage specificity using proteome based peptide libraries and mass spectrometry. Journal of proteomics. 2010;74(4): 401-10. PMID: 21156218
  • Guerreiro J, Lameu C, Oliveira E, Klitzke C, Melo R, Linares E, Augusto O, Fox J, Lebrun I, Serrano S, Camargo A. Argininosuccinate synthetase is a functional target for a snake venom anti-hypertensive peptide: role in arginine and nitric oxide production. The Journal of biological chemistry. 2009;284(30): 20022-33. PMID: 19491403
  • Li L, Dragulev B, Zigrino P, Mauch C, Fox J. The invasive potential of human melanoma cell lines correlates with their ability to alter fibroblast gene expression in vitro and the stromal microenvironment in vivo. International journal of cancer. Journal international du cancer. 2009;125(8): 1796-804. PMID: 19569239
  • Zigrino P, Kuhn I, Bäuerle T, Zamek J, Fox J, Neumann S, Licht A, Schorpp-Kistner M, Angel P, Mauch C. Stromal expression of MMP-13 is required for melanoma invasion and metastasis. The Journal of investigative dermatology. 2009;129(11): 2686-93. PMID: 19516266
  • Fox J, Serrano S. Exploring snake venom proteomes: multifaceted analyses for complex toxin mixtures. Proteomics. 2008;8(4): 909-20. PMID: 18203266
  • Fox J, Serrano S. Approaching the golden age of natural product pharmaceuticals from venom libraries: an overview of toxins and toxin-derivatives currently involved in therapeutic or diagnostic applications. Current pharmaceutical design. 2007;13(28): 2927-34. PMID: 17979737
  • Mayhew M, Jeffery E, Sherman N, Nelson K, Polefrone J, Pratt S, Shabanowitz J, Parsons J, Fox J, Hunt D, Horwitz A. Identification of phosphorylation sites in betaPIX and PAK1. Journal of cell science. 2007;120 3911-8. PMID: 17989089
  • Serrano S, Wang D, Shannon J, Pinto A, Polanowska-Grabowska R, Fox J. Interaction of the cysteine-rich domain of snake venom metalloproteinases with the A1 domain of von Willebrand factor promotes site-specific proteolysis of von Willebrand factor and inhibition of von Willebrand factor-mediated platelet aggregation. The FEBS journal. 2007;274(14): 3611-21. PMID: 17578514
  • Zigrino P, Steiger J, Fox J, Löffek S, Schild A, Nischt R, Mauch C. Role of ADAM-9 disintegrin-cysteine-rich domains in human keratinocyte migration. The Journal of biological chemistry. 2007;282(42): 30785-93. PMID: 17704059
  • Dragulev B, Bao Y, Ramos-Cerrillo B, Vazquez H, Olvera A, Stock R, Algaron A, Fox J. Upregulation of IL-6, IL-8, CXCL1, and CXCL2 dominates gene expression in human fibroblast cells exposed to Loxosceles reclusa sphingomyelinase D: insights into spider venom dermonecrosis. The Journal of investigative dermatology. 2006;127(5): 1264-6. PMID: 17139265
  • Serrano S, Kim J, Wang D, Dragulev B, Shannon J, Mann H, Veit G, Wagener R, Koch M, Fox J. The cysteine-rich domain of snake venom metalloproteinases is a ligand for von Willebrand factor A domains: role in substrate targeting. The Journal of biological chemistry. 2006;281(52): 39746-56. PMID: 17040908
  • Fox J, Serrano S. Structural considerations of the snake venom metalloproteinases, key members of the M12 reprolysin family of metalloproteinases. Toxicon : official journal of the International Society on Toxinology. 2005;45(8): 969-85. PMID: 15922769
  • Gallagher P, Bao Y, Prorock A, Zigrino P, Nischt R, Politi V, Mauch C, Dragulev B, Fox J. Gene expression profiling reveals cross-talk between melanoma and fibroblasts: implications for host-tumor interactions in metastasis. Cancer research. 2005;65(10): 4134-46. PMID: 15899804