University of Virginia School of Medicine Cell Biology Associate ProfessorAppointed: 1989 University of Virginia School of Medicine Biotechnology Training Program DirectorAppointed: 2000 |  |
QualificationsPh.D., McGill University, Anatomy, 1982. M.Sc., McGill University, Anatomy, 1979. B.Sc., McMaster University, Biology, 1976. Expertise and Research InterestsMy lab is interested in epithelial renewal, viability and secretion. We focus on the human prosecretory mitogen 'lacritin' (Sanghi et al, '01; Ma et al, `07), now known to be conserved in at least ten other species. As lacritin flows from secretory cells through ducts it may generate a proliferative/secretory field as a different unit of cellular renewal in nongermative epithelia where stem cell niches are not obvious and duplicating cells are diffusely distributed (Wang et al, `06). Lacritin is also expressed by transit amplifying cells of the cornea. Our exploration of lacritin cell targeting has discovered a novel `off/on' switch mechanism in which lacritin binding of the ubiquitous cell surface proteoglycan `syndecan-1' requires prior removal of heparan sulfate chains by `heparanase' (Ma et al, '06). This restricts lacritin activity to sites of heparanase expression, such as regions of exocrine cell migration, secretion, renewal, and inflammation. Binding is mutually specified by lacritin's C-terminal mitogenic domain and syndecan-1's N-terminus. No binding is seen to syndecans-2 or -4. In contrast other growth factors, such as FGF, Wnt, Hh, TGFbeta, amphiregulin and HGF, bind heparan sulfate chains. This is less selective since heparan sulfate chains are common to all syndecans and most other extracellular proteoglycans. Two lacritin alternative splice forms have been discovered (Ma et al, '07). Both are expected to be inactive based on functional analyses with lacritin deletion mutants. Our exploration of lacritin signaling has sketched out diverging G-alpha/PKCalpha/PLC/calcium/NFAT/COX2 and G-alpha/PKCalpha/PLD/mTOR pathways (Wang et al, '06). This implies upstream involvement of a G-protein coupled receptor to which lacritin can bind perhaps at higher affinity when complexed with syndecan-1. Much remains to be learned about NFAT and mTOR signaling in epithelia, and in particular how lacritin's rapid biphasic signaling is transformed into epithelial mitogenesis, and enhanced viability and secretion. The downstream COX2 signaling is intriguing. COX1/COX2 generation of prostaglandin E2 was recently reported by another group to regulate homeostasis in hematopoietic stem cells. A Lacritin Consortium of collaborating labs within Virginia (in Biomedical Engineering and Ophthalmology at UVa; in Biotechnology at JMU; and in Ocular Pharmacology at EVMS) and outside (Walter Reed Ophthalmology) meets several times a year. One area of joint interest is lacritin's potential as a secretogogue in the treatment of the common eye disease `dry eye'. This possible utility is preliminarily suggested by preclinical studies. Other ExpertiseAcademic Experience: - Secretary, Postgraduate Student's Society, McGill University, 1978-1979 - Winner, The C.P. Leblond Research Presentation Award for poster presentation, awarded by Canadian Assoc. of Anatomists, 1981 - Co-winner, The Ralph D. Lillie Award for best student presentation, American Histochemical Society, 1982 - Member, Local Arrangements Committee for 1986 Annual Meeting of American Society for Cell Biology - Organizer, Minisymposium on Basement Membrane for 8th Congress of Histochemistryand Cytochemistry, 1986 - Member, NIH International and Cooperative Projects Ad Hoc Study Section, 1989 and 1990 - Director, Department of Anatomy and Cell Biology Seminar Series, 1991 - 1992 - Organizer, 'Eminent Cell Biologists in Medicine' Seminar Series, 1991 - 1992. Funding Sought and Provided by Markey Center, NEN Dupont, Pfizer, Boehringer Mannheim, Fisher, Amicon, Baxter, Pharmacia, Hyclone and Gibco BRL. Seminar speakers: Drs. Robert Goldman, Marilyn Farquhar, George Palade, Mina Bissell, and Joan Ruderman Executive Committee, JDF Student Research Summer Program; Organizer, Diabetes Summer Research Seminar Series, 1991 - 1993 - Member, Council on Medical Education, 1992 - 1993 - Organizer, Matrix Group seminar series, 1992 - 1999 - Graduate Admissions Committee, Department of Cell Biology, 1997 - present - Faculty Search Committee, Department of Cell Biology, 1998 - 1999 Biopolymers Initiative Committee, Co-Medical School Representative, 1999 - present - Judge, Children's Medical Center Pediatric Research Day, 1993 - Grant Reviewer, Medical Research Council of Canada, 1992 and 1995 - Grant Reviewer, Louisiana Stimulus for Excellence in Research (NSF EPSCoR Program), 1994 - Volunteer in American Society for Cell BiologyLetters to Young People Program, 1994 - present - Session Moderator, Lacrimal Gland and Sjogren's Syndrome, 1994, Annual Meeting of Association for Research in Vision and Ophthalmology - Grant Reviewer, Department of Veterans Affairs, 1995 - Member, International Advisory Committee for the Second International Conference on the Lacrimal Gland, Tear Film and Dry Eye Syndromes Basic Science and Clinical Relevance, 1995-1996 - Member, International Advisory Committee for the Third International Conference on the Lacrimal Gland, Tear Film and Dry Eye Syndromes Basic Science and Clinical Relevance, 1999 - 2000 - Grant Reviewer, NSF, 1996 - Grant Reviewer (Ad hoc), NIH Visual Sciences A Study Section, 1996, 1998, 2003 - Grant Reviewer, Vanderbilt University School of Medicine Diabetes Research and Training Center Pilot Grant Proposal, 1996 - Member, Lacrimal Gland Study Group Steering Committee, May 1996 - 2001; Chair, 1999 - 2000. - Ad Hoc Reviewer, GCRC Advisory Committee, 1996 - present. - Grant Reviewer, Telethon Combatti La Distrofia Musculare E Le Altre Malattie Gentetiche, Rome Italy, 1997 - Member, Peer Reviewing Board, Telethon Combatti La Distrofia Musculare E Le Altre Malattie Gentetiche, Rome Italy, 1997 - present - Reviewer, Italian Ministry for University Research, 2000, 2001 - Elected to University of Virginia Faculty Senate, 1997 - 2001 - Reviewer, NIH Special Emphasis Panel, NIGMS, 1997; NEI, 1999, 2005; NIAR, 2000; NIDR, 2001. - Director and PI, UVa Biotechnology Training Program, 2000 - present. - Member, UVa School of Medicine Graduate Program Executive Committee, 2000 - present. - Guest Editorial Board Member, Investigative Ophthalmology and Visual Science, 2000, 2001. - Member, ARVO Commercial Relations Committee, 2001 - present. - Member, Medical and Scientific Advisory Board, Tear Film & Ocular Surface Society (TFOS), 2001 - 2005. - Visiting Associate Professor, University of Western Sydney, March 2003. - Admissions Chair, UVa Cell and Developmental Biology Program, 2003 - present. - Member, NEIBank Executive Advisory Committee, 2004 - present. - Virginia Biotechnology Educator of the Year Award, Virginia Biotechnology Association, 2004 - Councilor, Governing Board, Tear Film and Ocular Surface Society, 2005 - present. - Reviewer, NIH Anterior Eye Disease Study Section (ad hoc), 2005, 2008. - Member, NSU-NIH/CBBS Planning and Advisory Committee, 2006 - present. - Co-Moderator ARVO Poster Session, `Analysis and Functional Aspects of Tears and the Lacrimal Gland', May 2008. Future ResearchOngoing/new initiatives: Lacritin mutational, signaling and receptor studies. Collaborative preclinical studies. Industrial RelevanceLacritin as a natural topical Dry Eye therapeutic. KeywordsCOS Keywords:Biotechnology, Breast Cancer, Cell Biology, Extracellular Matrix, Gene Regulation, Immunology, Membranes, Monoclonal Antibodies, Morphogenesis, Peptides.Additional Terms:Basement Membrane, Cell Adhesion, Contact Lens, Dry Eye, Epithelial, Extracellular Matrix, Growth Factor, Integrin, Lacrimal, Laminin, Secretion, Sjogren's Syndrome.Languages(Reading, Writing, Speaking)French: (Basic, Basic, Basic) MembershipsAmerican Society for Cell Biology Association for Research in Vision and Ophthalmology Society for Developmental Biology Tear Film and Ocular Surface Society Honors and Awards2007-2008,
Thelma R. Swortzel Collaborative Research Award,
Thelma R. Swortzel Foundation
2007-2008,
NIH Director's Bridge Award,
National Institutes of Health (NIH)
2004-2004,
Virginia Biotechnology Educator of the Year Award,
VABio,
Virginia Biotechnology Association
1982, The Ralph D. Lillie Award,
American Histochemical Society
1981, The C. P. Leblond Research Presentation Award,
Canadian Assoc. of Anatomists
Previous Positions1988-1995, Assistant Professor,
University of Virginia
1986-1988, Visiting Associate,
National Institutes of Health (NIH)
1983-1986, Visiting Fellow,
National Institutes of Health (NIH)
1982-1983, Postdoctoral Fellow,
McGill University
PatentsOcular Tear Growth Factor-Like Protein,
Patent Number: 7320870,
2008,
Institution,
United States of America.
 Lacritin-Syndecan Interactions,
Patent Number: pending,
2006,
United States of America.
 Use of Lacritin in Promoting Ocular Cell Survival,
Patent Number: pending,
2004,
United States of America.
 Diagnostic for Sjogren's Syndrome,
Patent Number: 5895812,
1999,
Institution-owned,
United States of America.
 Polypeptide with laminin cell adhesion and morphogenesis activity,
Patent Number: 5696229,
1997,
Institution-owned,
United States of America.
 Funding Received- National Institutes of Health (NIH):
Modeling Novel Treatments for Dry Eye,
2007
to 2012.
- National Institutes of Health (NIH):
Structure and Function of Ocular Lacritin,
2002
to 2008.
- National Institutes of Health (NIH):
T32 GM08715 Biotechnology Training Program,
2000
to 2010.
Publications- Ma P, Wang N, McKown RL, Raab, RW, Laurie GW (2008) Focus on Molecules: Lacritin., Exp Eye Res., In Press
- Laurie GW, Olsakovsky LA, Conway BP, McKown RL, Kitagawa K, Nichols JJ (2008) Dry Eye and Designer Ophthalmics, OVS, In Press
- Wang, J., Wang, N., Xie, J., Walton, S.C., McKown, R.L., Raab, R.W., Ma, P., Beck, S.L., Coffman, G., Hussaini, I., and Laurie, G.W. (2006) Restricted epithelial proliferation by lacritin via PKCa-dependent NFAT and mTOR pathways., J. Cell Biol., 174 (5), 689-700
- Ma P, Beck SL, Raab R, McKown R, Coffman G, Utani A, Chirico WJ, Rapraeger A, Laurie GW (September, 2006) Heparanase deglycanation of syndecan-1 is required for binding of epithelial-restricted mitogen lacritin, J. Cell Biol., 174 (7), 1097-1106
- Ozyildirim AM, Wistow GJ, Gao J, Wang J, Dickinson DP, Frierson HF Jr, Laurie GW., The Lacrimal Gland Transcriptome Is An Unusually Rich Source of Rare and Poorly Characterized Gene Transcripts., Invest Ophthalmol Vis Sci., 46(5), 1572-80, May 2005
- Wang J, Laurie GW, Organogenesis of the exocrine gland, Developmental Biology, 273(1), 1-22, September 2004
 - 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, Journal of Molecular Biology, 319(3), 593-602, June 2002
 - 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, Journal of Biological Chemistry, 277(16), 13778-86, April 2002
 - Kumar R, Huebner A, Laurie GW, Genetic separation of the human lacritin gene ("LACRT") and triple A
(Allgrove) syndrome on 12q13, Advances in Experimental Medicine and Biology, 506(Pt A), 167-74, 2002
 - Sanghi S, Kumar R, Lumsden A, Dickinson D, Klepeis V, Trinkaus-Randall V, Frierson HF Jr, Laurie GW, cDNA and genomic cloning of lacritin, a novel secretion enhancing factor
from the human lacrimal gland, Journal of Molecular Biology, 310(1), 127-39, June 2001
 - 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, Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research., 12(2), 99-107, February 2001
 - Pogany G, Timar F, Olah 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, Oncology, 60(3), 274-81, 2001
 - Kumar R, Lumsden A, Ciclitira PJ, Ellis HJ, Laurie GW, Human genome search in celiac disease using gliadin cDNA as probe, Journal of Molecular Biology, 300(5), 1155-67, July 2000
 - Sanghi S, Kumar R, Walton S, Laurie GW, Quantitation of rat lacrimal secretion: a novel sandwich ELISA with high
sensitivity, Experimental Eye Research, 70(5), 651-8, May 2000
 - 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, The American Journal of Physiology, 275(1 Pt 1), C278-84, July 1998
 - 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, Advances in Experimental Medicine and Biology, 438, 49-54, 1998
 - Scholz E, Pogany G, Ganzler K, Laurie GW, Characterization of a basement membrane protein (BM180) using capillary electrophoresis, Journal of Capillary Electrophoresis, 4(6), 287-92, 1997
 - 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, The American Journal of Physiology, 272(3 Pt 1), L494-503, March 1997
 - Matter ML, Laurie GW, A putative sub-10-kDa basement membrane activity required for lung
alveolar formation in vitro, The American Journal of Physiology, 271(3 Pt 1), L489-94, September 1996
 - 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, The American Journal of Physiology, 270(6 Pt 1), C1743-50, June 1996
 - Caniggia I, Liu J, Han R, Wang J, Tanswell AK, Laurie G, Post M, Identification of receptors binding fibronectin and laminin on fetal rat
lung cells, The American Journal of Physiology, 270(3 Pt 1), L459-68, March 1996
 - Laurie GW, Ciclitira PJ, Ellis HJ, Pogany G, Immunological and partial sequence identity of mouse BM180 with wheat
alpha-gliadin, Biochemical and Biophysical Research Communications, 217(1), 10-5, December 1995
 - Chakravarti S, Horchar T, Jefferson B, Laurie GW, Hassell JR, Recombinant domain III of perlecan promotes cell attachment through its RGDS sequence, Journal of Biological Chemistry, 270(1), 404-9, January 1995
 - Matter ML, Laurie GW, A novel laminin E8 cell adhesion site required for lung alveolar formation
in vitro, Journal of Cell Biology, 124(6), 1083-90, March 1994
 - Laurie GW, Stone CM, Glass JD, Serum-free primary culture of harderian acinar cells, Experimental Eye Research, 58(3), 375-8, March 1994
 - Laurie GW, Glass JD, Ogle RA, Basement membrane modulation of stimulated secretion by lacrimal acinar
cells, Advances in Experimental Medicine and Biology, 350, 37-44, 1994
 - 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, Current Eye Research, 11(9), 923-7, September 1992
 - Stone C M, Laurie G W, Cellular expression of collagen IV mRNA in eye, Experimental Eye Research, 53(5), 677-80, November 1991
 - Laurie G W, Stone C M, Yamada Y, Elevated 32-kDa LBP and low laminin mRNA expression in developing mouse cerebrum., Differentiation, 46(3), 173-9, April 1991
 - Taub M, Laurie GW, Martin GR, Kleinman HK, Altered basement membrane protein biosynthesis by primary cultures of cpk/cpk mouse kidney, Kidney International, 37(4), 1090-7, April 1990
 - 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, Journal of Cell Biology, 109(3), 1351-62, September 1989
 - Laurie GW, Inoue S, Bing JT, Hassell JR, Visualization of the large heparan sulfate proteoglycan from basement membrane, American Journal of Anatomy, 181(3), 320-6, March 1988
 - 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, Laboratory Investigation, 58(3), 262-9, March 1988
 - 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, Proceedings of the National Academy of Sciences (USA), 83(14), 5126-30, July 1986
 - 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, Journal of Molecular Biology, 189(1), 205-16, May 1986
 - Hassell JM, Noonan DM, Ledbetter SR, Laurie GW, Biosynthesis and structure of the basement membrane proteoglycan containing heparan sulphate side-chains, Ciba Foundation Symposium, 124, 204-22, 1986
 - Kleinman HK, McGarvey ML, Hassell JR, Star VL, Cannon FB, Laurie GW, Martin GR, Basement membrane complexes with biological activity, Biochemistry, 25(2), 312-8, January 1986
 - 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, Proceedings of the National Academy of Sciences (USA), 82(11), 3824-8, June 1985
 - Laurie GW, Lack of heparan sulfate proteoglycan in a discontinuous and irregular placental basement membrane, Developmental Biology, 108(2), 299-309, April 1985
 - Laurie GW, Leblond CP, Basement membrane nomenclature [letter], Nature, 313(6000), 272, January 1985
 - Kleinman HK, Cannon FB, Laurie GW, Hassell JR, Aumailley M, Terranova VP, Martin GR, DuBois-Dalcq M, Biological activities of laminin, Journal of Cellular Biochemistry, 27(4), 317-25, 1985
 - 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 th, American Journal of Anatomy, 169(4), 463-81, April 1984
 - Inoue S, Leblond CP, Laurie GW, Ultrastructure of Reichert's membrane, a multilayered basement membrane in the parietal wall of the rat yolk sac, Journal of Cell Biology, 97(5 Pt 1), 1524-37, November 1983
 - 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, American Journal of Anatomy, 167(1), 71-82, May 1983
 - Laurie GW, Leblond CP, What is known of the production of basement membrane components, Journal of Histochemistry and Cytochemistry, 31(1A Suppl), 159-63, January 1983
 - 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, Journal of Histochemistry and Cytochemistry, 30(10), 973-82, October 1982
 - 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, Journal of Histochemistry and Cytochemistry, 30(10), 983-90, October 1982
 - Laurie GW, Leblond CP, Martin GR, Localization of type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin to the basal lamina of basement membranes, Journal of Cell Biology, 95(1), 340-4, October 1982
 - 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, Journal of Histochemistry and Cytochemistry, 30(10), 991-8, October 1982
 - Laurie GW, Leblond CP, Cournil I, Martin GR, Immunohistochemical evidence for the intracellular formation of basement membrane collagen (type IV) in developing tissues, Journal of Histochemistry and Cytochemistry, 28(12), 1267-74, December 1980

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