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Laurie, Gordon

Gordon Laurie

Primary Appointment

Cell Biology

Contact Information

PO Box 800732
Charlottesville, VA 22908-0732
Telephone: 434-924-5250
Fax: 434-982-3912
Email: gwl6s@virginia.edu
Website: http://people.virginia.edu/~gwl6s/

Research Interests

Role of Prosecretory Mitogen 'Lacritin' in Epithelial Homeostasis, Secretion and Innate Defense

Research Description

My lab is interested in epithelial homeostasis, secretion and innate defense. We focus on the human prosecretory mitogen 'lacritin' that we discovered and named out of an unbiased screen for factors regulating ocular tearing (Sanghi et al, J Mol Biol '01). Tears are responsible for homeostasis of the surface of the eye and are essential for innate defense (Karnati et al, Exp Eye Res '13). Both functions are in whole or part contributed by lacritin (Wang et al, J Biol Chem ?13) or by cleavage potentiated fragments of lacritin (McKown et al, J Biol Chem, '14). Truncation and point mutational analysis narrowed the active site in lacritin to an amphipathic alpha helix (Wang et al, J Cell Biol ?06; J Biol Chem ?13), represented by the nineteen amino acid synthetic peptide 'N-94/C-6' - now the subject of a 201 patient, 25 site randomized, placebo controlled phase 2 clinical trial in 'dry eye', the most common eye disease. The trial is sponsored by 'TearSolutions, Inc.' that I cofounded in 2013. Mass spec reveals that N-94/C-6-containing peptides are in plasma and cerebral spinal fluid, implying a potentially very broad hormone-like benefit. New areas of research under exploration include: (i) the lacritin signaling receptor and associated mediators via APEX2 labeling, and via a CRISPR/Cas9 genome-wide screen in collaboration with the Broad Institute, (ii) pro-homeostatic, and sensitivity targeting of IPSC-derived sensory neurons, (iii) lacritin?s cleavage-potentiated bactericidal activity (McKown et al, J Biol Chem '14) represented by the lacritin peptide N-104 (the subject of this application), and (iv) a potential benefit in restoring pancreatic islet function in type 1 diabetes. In 2002, I organized the multi-institutional Lacritin Consortium of collaborating labs (UVa, James Madison University, Eastern Virginia Medical School, Harvard University, University of Illinois at Chicago, Johns Hopkins, UCSF, UC-Berkeley, US Army at Fort Belvoir and others). The Consortium has continuously at least two times a year since to share data and explore new projects.

Selected Publications

Wang W, Lee C, Pastuszka M, Laurie GW, MacKay JA, Thermally-Responsive Loading and Release of Elastin-Like Polypeptides from Contact Lenses., 2019; Pharmaceutics. 11(5) PMID: 31067782 |

Rao P, McKown RL, Laurie GW, Suvas S, Development of lacrimal gland inflammation in the mouse model of herpes stromal keratitis., 2019; Experimental eye research. 184() 101-106 PMID: 31009613 |

Willcox MDP, Arg?eso P, Georgiev GA, Holopainen JM, Laurie GW, Millar TJ, Papas EB, Rolland JP, Schmidt TA, Stahl U, Suarez T, Subbaraman LN, U?akhan O?, Jones L, TFOS DEWS II Tear Film Report., 2017; The ocular surface. 15(3) 366-403 PMID: 28736338 | PMCID: PMC6035753

Laurie GW, Leblond CP, What is Known of the Production of Basement Membrane Components 12., 2017; The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 31(1) 159-163 PMID: 28054851 |

Wang W, Jashnani A, Aluri SR., Gustafson JA., Hsueh PY., Yarber F, McKown RL., Laurie GW., Hamm-Alvarez SF., MacKay JA., A thermo-responsive protein treatment for dry eyes, ; J Control Release. 199() 156-167 | PMCID: PMC4456095

Ferguson TA, Laurie GW, Introduction to Autophagy in the Eye (or "What's Eatin' You?")., 2015; Experimental eye research. 144() 1-3 PMID: 26348132 | PMCID: PMC4777279

Karnati R, Talla V, Peterson K, Laurie GW, Lacritin and other autophagy associated proteins in ocular surface health., 2015; Experimental eye research. 144() 4-13 PMID: 26318608 | PMCID: PMC4698016

Wang W, Jashnani A, Aluri SR, Gustafson JA, Hsueh PY, Yarber F, McKown RL, Laurie GW, Hamm-Alvarez SF, MacKay JA, A thermo-responsive protein treatment for dry eyes., 2014; Journal of controlled release : official journal of the Controlled Release Society. 199() 156-67 PMID: 25481446 | PMCID: PMC4456095

McKown RL, Coleman Frazier EV, Zadrozny KK, Deleault AM, Raab RW, Ryan DS, Sia RK, Lee JK, Laurie GW, A cleavage-potentiated fragment of tear lacritin is bactericidal., 2014; The Journal of biological chemistry. 289(32) 22172-82 PMID: 24942736 | PMCID: PMC4139230

Vijmasi T, Chen FY, Balasubbu S, Gallup M, McKown RL, Laurie GW, McNamara NA, Topical administration of lacritin is a novel therapy for aqueous-deficient dry eye disease., 2014; Investigative ophthalmology & visual science. 55(8) 5401-9 PMID: 25034600 | PMCID: PMC4148924

Feng MM, Baryla J, Liu H, Laurie GW, McKown RL, Ashki N, Bhayana D, Hutnik CM, Cytoprotective effect of lacritin on human corneal epithelial cells exposed to benzalkonium chloride in vitro., 2014; Current eye research. 39(6) 604-10 PMID: 24401093 | PMCID: PMC4371594

McKown RL, Raab RW, Kachelries P, Caldwell S, Laurie GW, Conserved regional 3' grouping of rare codons in the coding sequence of ocular prosecretory mitogen lacritin., 2013; Investigative ophthalmology & visual science. 54(3) 1979-87 PMID: 23422824 | PMCID: PMC3604909

Velez V F, Romano JA, McKown RL, Green K, Zhang L, Raab RW, Ryan DS, Hutnik CM, Frierson HF, Laurie GW, Tissue transglutaminase is a negative regulator of monomeric lacritin bioactivity., 2013; Investigative ophthalmology & visual science. 54(3) 2123-32 PMID: 23425695 | PMCID: PMC3621506

Zhang Y, Wang N, Raab RW, McKown RL, Irwin JA, Kwon I, van Kuppevelt TH, Laurie GW, Targeting of heparanase-modified syndecan-1 by prosecretory mitogen lacritin requires conserved core GAGAL plus heparan and chondroitin sulfate as a novel hybrid binding site that enhances selectivity., 2013; The Journal of biological chemistry. 288(17) 12090-101 PMID: 23504321 | PMCID: PMC3636894

Wang N, Zimmerman K, Raab RW, McKown RL, Hutnik CM, Talla V, Tyler MF, Lee JK, Laurie GW, Lacritin rescues stressed epithelia via rapid forkhead box O3 (FOXO3)-associated autophagy that restores metabolism., 2013; The Journal of biological chemistry. 288(25) 18146-61 PMID: 23640897 | PMCID: PMC3689958

Karnati R, Laurie DE, Laurie GW, Lacritin and the tear proteome as natural replacement therapy for dry eye., 2013; Experimental eye research. 117() 39-52 PMID: 23769845 | PMCID: PMC3844047

Laurie DE, Splan RK, Green K, Still KM, McKown RL, Laurie GW, Detection of prosecretory mitogen lacritin in nonprimate tears primarily as a C-terminal-like fragment., 2012; Investigative ophthalmology & visual science. 53(10) 6130-6 PMID: 22871838 | PMCID: PMC3441044

Seifert K, Gandia NC, Wilburn JK, Bower KS, Sia RK, Ryan DS, Deaton ML, Still KM, Vassilev VC, Laurie GW, McKown RL, Tear lacritin levels by age, sex, and time of day in healthy adults., 2012; Investigative ophthalmology & visual science. 53(10) 6610-6 PMID: 22918641 | PMCID: PMC3460390

Zhang Y, McKown RL, Raab RW, Rapraeger AC, Laurie GW, Focus on molecules: syndecan-1., 2010; Experimental eye research. 93(4) 329-30 PMID: 20599970 | PMCID: PMC2955988

Zhang Y, Ryan DS, Bower KS, Ilan N, Vlodavsky I, Laurie GW, Focus on molecules: heparanase., 2010; Experimental eye research. 91(4) 476-7 PMID: 20478306 | PMCID: PMC2933305

Samudre S, Lattanzio FA, Lossen V, Hosseini A, Sheppard JD, McKown RL, Laurie GW, Williams PB, Lacritin, a novel human tear glycoprotein, promotes sustained basal tearing and is well tolerated., 2010; Investigative ophthalmology & visual science. 52(9) 6265-70 PMID: 21087963 | PMCID: PMC3176019

McKown RL, Wang N, Raab RW, Karnati R, Zhang Y, Williams PB, Laurie GW, Lacritin and other new proteins of the lacrimal functional unit., 2008; Experimental eye research. 88(5) 848-58 PMID: 18840430 | PMCID: PMC2712882

Laurie GW, Olsakovsky LA, Conway BP, McKown RL, Kitagawa K, Nichols JJ, Dry eye and designer ophthalmics., 2008; Optometry and vision science : official publication of the American Academy of Optometry. 85(8) 643-52 PMID: 18677231 | PMCID: PMC2815326

Ma P, Wang N, McKown RL, Raab RW, Laurie GW, Focus on molecules: lacritin., 2007; Experimental eye research. 86(3) 457-8 PMID: 17412322 | PMCID: PMC2277456

Ma P, Beck SL, Raab RW, McKown RL, Coffman GL, Utani A, Chirico WJ, Rapraeger AC, Laurie GW, Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin., 2006; The Journal of cell biology. 174(7) 1097-106 PMID: 16982797 | PMCID: PMC1666580

Wang J, Wang N, Xie J, Walton SC, McKown RL, Raab RW, Ma P, Beck SL, Coffman GL, Hussaini IM, Laurie GW, Restricted epithelial proliferation by lacritin via PKCalpha-dependent NFAT and mTOR pathways., 2006; The Journal of cell biology. 174(5) 689-700 PMID: 16923831 | PMCID: PMC1761701

Ozyildirim AM, Wistow GJ, Gao J, Wang J, Dickinson DP, Frierson HF, Laurie GW, The lacrimal gland transcriptome is an unusually rich source of rare and poorly characterized gene transcripts., 2005; Investigative ophthalmology & visual science. 46(5) 1572-80 PMID: 15851553 |

Wang J, Laurie GW, Organogenesis of the exocrine gland., 2004; Developmental biology. 273(1) 1-22 PMID: 15302594 |

Kumar R, Huebner A, Laurie GW, Genetic separation of the human lacritin gene ("LACRT") and triple A (Allgrove) syndrome on 12q13., 2003; Advances in experimental medicine and biology. 506(0) 167-74 PMID: 12613904 |

Faisal Khan KM, Laurie GW, McCaffrey TA, Falcone DJ, Exposure of cryptic domains in the alpha 1-chain of laminin-1 by elastase stimulates macrophages urokinase and matrix metalloproteinase-9 expression., 2002; The Journal of biological chemistry. 277(16) 13778-86 PMID: 11827968 |

Kumar R, Eastwood AL, Brown ML, Laurie GW, Human genome search in celiac disease: mutated gliadin T-cell-like epitope in two human proteins promotes T-cell activation., 2002; Journal of molecular biology. 319(3) 593-602 PMID: 12054857 |

Pog?ny G, Tim?r F, Ol?h J, Harisi R, Polony G, Paku S, Bocsi J, Jeney A, Laurie GW, Role of the basement membrane in tumor cell dormancy and cytotoxic resistance., 2001; Oncology. 60(3) 274-81 PMID: 11340380 |

Edlund M, Miyamoto T, Sikes RA, Ogle R, Laurie GW, Farach-Carson MC, Otey CA, Zhau HE, Chung LW, Integrin expression and usage by prostate cancer cell lines on laminin substrata., 2001; Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research. 12(2) 99-107 PMID: 11243469 |

Sanghi S, Kumar R, Lumsden A, Dickinson D, Klepeis V, Trinkaus-Randall V, Frierson HF, Laurie GW, cDNA and genomic cloning of lacritin, a novel secretion enhancing factor from the human lacrimal gland., 2001; Journal of molecular biology. 310(1) 127-39 PMID: 11419941 |

Kumar R, Lumsden A, Ciclitira PJ, Ellis HJ, Laurie GW, Human genome search in celiac disease using gliadin cDNA as probe., 2000; Journal of molecular biology. 300(5) 1155-67 PMID: 10903861 |

Sanghi S, Kumar R, Walton S, Laurie GW, Quantitation of rat lacrimal secretion: a novel sandwich ELISA with high sensitivity., 2000; Experimental eye research. 70(5) 651-8 PMID: 10870523 |

Scholz E, Pogany G, Ganzler K, Laurie GW, Characterization of a basement membrane protein (BM180) using capillary electrophoresis., 1998; Journal of capillary electrophoresis. 4(6) 287-92 PMID: 9827419 |

Chen L, Glass JD, Walton SC, Laurie GW, Role of laminin-1, collagen IV, and an autocrine factor(s) in regulated secretion by lacrimal acinar cells., 1998; The American journal of physiology. 275(1) C278-84 PMID: 9688859 |

Asrani AC, Lumsden AJ, Kumar R, Laurie GW, Gene cloning of BM180, a lacrimal gland enriched basement membrane protein with a role in stimulated secretion., 1998; Advances in experimental medicine and biology. 438() 49-54 PMID: 9634862 |

Chen L, Shick V, Matter ML, Laurie SM, Ogle RC, Laurie GW, Laminin E8 alveolarization site: heparin sensitivity, cell surface receptors, and role in cell spreading., 1997; The American journal of physiology. 272(3) L494-503 PMID: 9124607 |

Matter ML, Laurie GW, A putative sub-10-kDa basement membrane activity required for lung alveolar formation in vitro., 1996; The American journal of physiology. 271(3) L489-94 PMID: 8843800 |

Laurie GW, Glass JD, Ogle RA, Stone CM, Sluss JR, Chen L, "BM180": a novel basement membrane protein with a role in stimulus-secretion coupling by lacrimal acinar cells., 1996; The American journal of physiology. 270(6) C1743-50 PMID: 8764158 |

Laurie GW, Ciclitira PJ, Ellis HJ, Pogany G, Immunological and partial sequence identity of mouse BM180 with wheat alpha-gliadin., 1995; Biochemical and biophysical research communications. 217(1) 10-5 PMID: 8526896 |

Chakravarti S, Horchar T, Jefferson B, Laurie GW, Hassell JR, Recombinant domain III of perlecan promotes cell attachment through its RGDS sequence., 1995; The Journal of biological chemistry. 270(1) 404-9 PMID: 7814401 |

Laurie GW, Stone CM, Glass JD, Serum-free primary culture of harderian acinar cells., 1994; Experimental eye research. 58(3) 375-8 PMID: 8174657 |

Matter ML, Laurie GW, A novel laminin E8 cell adhesion site required for lung alveolar formation in vitro., 1994; The Journal of cell biology. 124(6) 1083-90 PMID: 8132708 | PMCID: PMC2119975

Laurie GW, Glass JD, Ogle RA, Basement membrane modulation of stimulated secretion by lacrimal acinar cells., 1994; Advances in experimental medicine and biology. 350() 37-44 PMID: 8030505 |

Stone CM, Laurie GW, Cell-specific expression of LBP-32 mRNA in retina and other locations of newborn mouse eye as revealed by in situ hybridization., 1992; Current eye research. 11(9) 923-7 PMID: 1424732 |

Stone CM, Laurie GW, Cellular expression of collagen IV mRNA in eye., 1991; Experimental eye research. 53(5) 677-80 PMID: 1743266 |

Laurie GW, Stone CM, Yamada Y, Elevated 32-kDa LBP and low laminin mRNA expression in developing mouse cerebrum., 1991; Differentiation; research in biological diversity. 46(3) 173-9 PMID: 1833253 |

Taub M, Laurie GW, Martin GR, Kleinman HK, Altered basement membrane protein biosynthesis by primary cultures of cpk/cpk mouse kidney., 1990; Kidney international. 37(4) 1090-7 PMID: 2160557 |

Laurie GW, Horikoshi S, Killen PD, Segui-Real B, Yamada Y, In situ hybridization reveals temporal and spatial changes in cellular expression of mRNA for a laminin receptor, laminin, and basement membrane (type IV) collagen in the developing kidney., 1989; The Journal of cell biology. 109(3) 1351-62 PMID: 2527859 | PMCID: PMC2115755

Ebihara I, Killen PD, Laurie GW, Huang T, Yamada Y, Martin GR, Brown KS, Altered mRNA expression of basement membrane components in a murine model of polycystic kidney disease., 1988; Laboratory investigation; a journal of technical methods and pathology. 58(3) 262-9 PMID: 3279260 |

Laurie GW, Inoue S, Bing JT, Hassell JR, Visualization of the large heparan sulfate proteoglycan from basement membrane., 1988; The American journal of anatomy. 181(3) 320-6 PMID: 2452565 |

Chandrasekhar S, Laurie GW, Cannon FB, Martin GR, Kleinman HK, In vitro regulation of cartilage matrix assembly by a Mr 54,000 collagen-binding protein., 1986; Proceedings of the National Academy of Sciences of the United States of America. 83(14) 5126-30 PMID: 3014533 | PMCID: PMC323903

Laurie GW, Bing JT, Kleinman HK, Hassell JR, Aumailley M, Martin GR, Feldmann RJ, Localization of binding sites for laminin, heparan sulfate proteoglycan and fibronectin on basement membrane (type IV) collagen., 1986; Journal of molecular biology. 189(1) 205-16 PMID: 2946868 |

Kleinman HK, McGarvey ML, Hassell JR, Star VL, Cannon FB, Laurie GW, Martin GR, Basement membrane complexes with biological activity., 1986; Biochemistry. 25(2) 312-8 PMID: 2937447 |

Hassell JM, Noonan DM, Ledbetter SR, Laurie GW, Biosynthesis and structure of the basement membrane proteoglycan containing heparan sulphate side-chains., 1986; Ciba Foundation symposium. 124() 204-22 PMID: 2949947 |

Bohnsack JF, Tenner AJ, Laurie GW, Kleinman HK, Martin GR, Brown EJ, The C1q subunit of the first component of complement binds to laminin: a mechanism for the deposition and retention of immune complexes in basement membrane., 1985; Proceedings of the National Academy of Sciences of the United States of America. 82(11) 3824-8 PMID: 2987948 | PMCID: PMC397880

Laurie GW, Lack of heparan sulfate proteoglycan in a discontinuous and irregular placental basement membrane., 1985; Developmental biology. 108(2) 299-309 PMID: 2934285 |

Laurie GW, Leblond CP, Basement membrane nomenclature., 1985; Nature. 313(6000) 272 PMID: 3969140 |

Kleinman HK, Cannon FB, Laurie GW, Hassell JR, Aumailley M, Terranova VP, Martin GR, DuBois-Dalcq M, Biological activities of laminin., 1985; Journal of cellular biochemistry. 27(4) 317-25 PMID: 3889019 |

Laurie GW, Leblond CP, Inoue S, Martin GR, Chung A, Fine structure of the glomerular basement membrane and immunolocalization of five basement membrane components to the lamina densa (basal lamina) and its extensions in both glomeruli and tubules of the rat kidney., 1984; The American journal of anatomy. 169(4) 463-81 PMID: 6375342 |

Laurie GW, Leblond CP, Martin GR, Light microscopic immunolocalization of type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin in the basement membranes of a variety of rat organs., 1983; The American journal of anatomy. 167(1) 71-82 PMID: 6346854 |

Laurie GW, Leblond CP, What is known of the production of basement membrane components., 1983; The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 31(1) 159-63 PMID: 6186721 |

Inou? S, Leblond CP, Laurie GW, Ultrastructure of Reichert's membrane, a multilayered basement membrane in the parietal wall of the rat yolk sac., 1983; The Journal of cell biology. 97(5) 1524-37 PMID: 6226670 | PMCID: PMC2112687

Laurie GW, Leblond CP, Martin GR, Silver MH, Intracellular localization of basement membrane precursors in the endodermal cells of the rat parietal yolk sac. III. Immunostaining for laminin and its precursors., 1982; The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 30(10) 991-8 PMID: 6752265 |

Laurie GW, Leblond CP, Martin GR, Intracellular localization of basement membrane precursors in the endodermal cells of the rat parietal yolk sac. II. Immunostaining for type IV collagen and its precursors., 1982; The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 30(10) 983-90 PMID: 6752264 |

Laurie GW, Leblond CP, Intracellular localization of basement membrane precursors in the endodermal cells of the rat parietal yolk sac. I. Ultrastructure and phosphatase activity of endodermal cells., 1982; The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 30(10) 973-82 PMID: 6290565 |

Laurie GW, Leblond CP, Martin GR, Localization of type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin to the basal lamina of basement membranes., 1982; The Journal of cell biology. 95(1) 340-4 PMID: 6216257 | PMCID: PMC2112347

Laurie GW, Leblond CP, Cournil I, Martin GR, Immunohistochemical evidence for the intracellular formation of basement membrane collagen (type IV) in developing tissues., 1980; The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 28(12) 1267-74 PMID: 6164715 |