Gordon W. Laurie

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Primary Appointment

Professor, Cell Biology

Education

  • BS, Biology, McMaster University
  • MS, Cell Biology, McGill University, Montreal, P.Q., CANADA
  • PhD, Cell Biology, McGill University, Montreal, P.Q., CANADA

Research Disciplines

Biochemistry, Biotechnology, Cell and Developmental Biology, Development, Stem Cells & Regeneration, Metabolism, Molecular Pharmacology, Neuroscience, Translational Science

Research Interests

Restoration of Homeostasis in Disease

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 â13) 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 â06; J Biol Chem â13), 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) lacritinâs 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.

Personal Statement

We focus on homeostasis, particularly epithelial and neuronal homeostasis. 'Dry eye' disease is a disruption of ocular homeostasis. No one has addressed the biological basis of dry eye, except for its downstream inflammation. We did so and discovered/named 'lacritin' out of an unbiased biochemical screen using an in vitro tear secretion end point assay - later replicated in vivo. Independent of its activity as a tear secretagogue, lacritin was also found to counter inflammatory cytokine-induced death by transiently accelerating autophagy and restoring oxidative phosphorylation. Both activities are rationale for a large phase 2 clinical trial nationwide. Interestingly, lacritin's active domain is represented as fragments in plasma and CSF, raising the possibility that other organs may benefit.

Training

  • Biotechnology Training Grant

Selected Publications

2024

Sharifian Gh, M., Norouzi, F., Sorci, M., Zaid, T. S., Pier, G. B., Achimovich, A., . . . Laurie, G. W. (2024). Targeting Iron - Respiratory Reciprocity Promotes Bacterial Death.. bioRxiv. doi:10.1101/2024.03.01.582947

2023

Liton, P. B., Boesze-Battaglia, K., Boulton, M. E., Boya, P., Ferguson, T. A., Ganley, I. G., . . . Zacks, D. N. (2023). AUTOPHAGY IN THE EYE: FROM PHYSIOLOGY TO PATHOPHYSOLOGY.. Autophagy reports, 2(1), 2178996. doi:10.1080/27694127.2023.2178996

2022

Dias-Teixeira, K. L., Sharifian, G. M., Romano, J., Norouzi, F., & Laurie, G. W. (2022). Autophagy in the normal and diseased cornea. EXPERIMENTAL EYE RESEARCH, 225. doi:10.1016/j.exer.2022.109274

Tauber, J., Laurie, G. W., Parsons, E. C., Odrich, M. G., & Lacripep, S. G. (2023). Lacripep for the Treatment of Primary Sjogren-Associated Ocular Surface Disease: Results of the First-In-Human Study. CORNEA, 42(7), 847-857. doi:10.1097/ICO.0000000000003091

2021

Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., . . . Tong, C. -K. (2021). Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). AUTOPHAGY, 17(1), 1-382. doi:10.1080/15548627.2020.1797280

2020

Georgiev, G. A., Gh, M. S., Romano, J., Teixeira, K. L. D., Struble, C., Ryan, D. S., . . . Laurie, G. W. (2021). Lacritin proteoforms prevent tear film collapse and maintain epithelial homeostasis. JOURNAL OF BIOLOGICAL CHEMISTRY, 296. doi:10.1074/jbc.RA120.015833

Lee, C., Edman, M. C., Laurie, G. W., Hamm-Alvarez, S. F., & MacKay, J. A. (2020). Biosynthesized Multivalent Lacritin Peptides Stimulate Exosome Production in Human Corneal Epithelium. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21(17). doi:10.3390/ijms21176157

Justis, B. M., Coburn, C. E., Tyler, E. M., Showalter, R. S., Dissler, B. J., Li, M., . . . McKown, R. L. (2020). Development of a Quantitative Immunoassay for Tear Lacritin Proteoforms. TRANSLATIONAL VISION SCIENCE & TECHNOLOGY, 9(9). doi:10.1167/tvst.9.9.13

Dias-Teixeira, K., Horton, X., McKown, R., Romano, J., & Laurie, G. W. (2020). The Lacritin-Syndecan-1-Heparanase Axis in Dry Eye Disease. HEPARANASE: FROM BASIC RESEARCH TO CLINICAL APPLICATIONS, 1221, 747-757. doi:10.1007/978-3-030-34521-1_31

2019

Wang, W., Lee, C., Pastuszka, M., Laurie, G. W., & MacKay, J. A. (2019). Thermally-Responsive Loading and Release of Elastin-Like Polypeptides from Contact Lenses. PHARMACEUTICS, 11(5). doi:10.3390/pharmaceutics11050221

Rao, P., McKown, R. L., Laurie, G. W., & Suvas, S. (2019). Development of lacrimal gland inflammation in the mouse model of herpes stromal keratitis. EXPERIMENTAL EYE RESEARCH, 184, 101-106. doi:10.1016/j.exer.2019.04.022

2017

Willcox, M. D. P., Argueso, P., Georgiev, G. A., Holopainen, J. M., Laurie, G. W., Millar, T. J., . . . Jones, L. (2017). TFOS DEWS II Tear Film Report. OCULAR SURFACE, 15(3), 366-403. doi:10.1016/j.jtos.2017.03.006

2016

Erratum. (2016). Autophagy, 12(2), 443. doi:10.1080/15548627.2016.1147886

Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Arozena, A. A., . . . Zughaier, S. M. (2016). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). AUTOPHAGY, 12(1), 1-222. doi:10.1080/15548627.2015.1100356

2015

Ferguson, T. A., & Laurie, G. W. (2016). Introduction to Autophagy in the Eye (or "What's Eatin' You?"). EXPERIMENTAL EYE RESEARCH, 144, 1-3. doi:10.1016/j.exer.2015.09.001

Karnati, R., Talla, V., Peterson, K., & Laurie, G. W. (2016). Lacritin and other autophagy associated proteins in ocular surface health. EXPERIMENTAL EYE RESEARCH, 144, 4-13. doi:10.1016/j.exer.2015.08.015

2014

Wang, W., Jashnani, A., Aluri, S. R., Gustafson, J. A., Hsueh, P. -Y., Yarber, F., . . . MacKay, J. A. (2015). A thermo-responsive protein treatment for dry eyes. JOURNAL OF CONTROLLED RELEASE, 199, 156-167. doi:10.1016/j.jconrel.2014.11.016

Vijmasi, T., Chen, F. Y. T., Balasubbu, S., Gallup, M., McKown, R. L., Laurie, G. W., & McNamara, N. A. (2014). Topical Administration of Lacritin Is a Novel Therapy for Aqueous-Deficient Dry Eye Disease. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 55(8), 5401-5409. doi:10.1167/iovs.14-13924

McKown, R. L., Frazier, E. V. C., Zadrozny, K. K., Deleault, A. M., Raab, R. W., Ryan, D. S., . . . Laurie, G. W. (2014). A Cleavage-potentiated Fragment of Tear Lacritin Is Bactericidal. JOURNAL OF BIOLOGICAL CHEMISTRY, 289(32), 22172-22182. doi:10.1074/jbc.M114.570143

Feng, M. M., Baryla, J., Liu, H., Laurie, G. W., McKown, R. L., Ashki, N., . . . Hutnik, C. M. L. (2014). Cytoprotective Effect of Lacritin on Human Corneal Epithelial Cells Exposed to Benzalkonium Chloride In Vitro. CURRENT EYE RESEARCH, 39(6), 604-610. doi:10.3109/02713683.2013.859275

2013

Karnati, R., Laurie, D. E., & Laurie, G. W. (2013). Lacritin and the tear proteome as natural replacement therapy for dry eye. EXPERIMENTAL EYE RESEARCH, 117, 39-52. doi:10.1016/j.exer.2013.05.020

Wang, N., Zimmerman, K., Raab, R. W., McKown, R. L., Hutnik, C. M. L., Talla, V., . . . Laurie, G. W. (2013). Lacritin Rescues Stressed Epithelia via Rapid Forkhead Box O3 (FOXO3)-associated Autophagy That Restores Metabolism. JOURNAL OF BIOLOGICAL CHEMISTRY, 288(25), 18146-18161. doi:10.1074/jbc.M112.436584

Laurie, D. E., Splan, R. K., Still, K. M., McKown, R. L., & Laurie, G. W. (2013). Equine tears contain the prosecretory mitogen lacritin primarily as a C-terminal-like fragment. Journal of Equine Veterinary Science, 33(5), 360-361. doi:10.1016/j.jevs.2013.03.094

McKown, R. L., Raab, R. W., Kachelries, P., Caldwell, S., & Laurie, G. W. (2013). Conserved Regional 3â² Grouping of Rare Codons in the Coding Sequence of Ocular Prosecretory Mitogen Lacritin. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 54(3), 1979-1987. doi:10.1167/iovs.12-10740

Zhang, Y., Wang, N., Raab, R. W., McKown, R. L., Irwin, J. A., Kwon, I., . . . Laurie, G. W. (2013). 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. JOURNAL OF BIOLOGICAL CHEMISTRY, 288(17), 12090-12101. doi:10.1074/jbc.M112.422717

Velez, F. V., Romano, J. A., McKown, R. L., Green, K., Zhang, L., Raab, R. W., . . . Laurie, G. W. (2013). Tissue Transglutaminase Is a Negative Regulator of Monomeric Lacritin Bioactivity. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 54(3), 2123-2132. doi:10.1167/iovs.12-11488

2012

Seifert, K., Gandia, N. C., Wilburn, J. K., Bower, K. S., Sia, R. K., Ryan, D. S., . . . McKown, R. L. (2012). Tear Lacritin Levels by Age, Sex, and Time of Day in Healthy Adults. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 53(10), 6610-6616. doi:10.1167/iovs.11-8729

Laurie, D. E., Splan, R. K., Green, K., Still, K. M., McKown, R. L., & Laurie, G. W. (2012). Detection of Prosecretory Mitogen Lacritin in Nonprimate Tears Primarily as a C-Terminal-Like Fragment. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 53(10), 6130-6136. doi:10.1167/iovs.11-8567

2011

SAMUDRE, S., LATTANZIO, F., WILLIAMS, P., MCKOWN, R., & LAURIE, G. (2011). Effect of lacritin, a novel glycoprotein, on ocular surface and tear film integrity. Acta Ophthalmologica, 89(s248), 0. doi:10.1111/j.1755-3768.2011.460.x

Samudre, S., Lattanzio, F. A. J., Lossen, V., Hosseini, A., Sheppard, J. D. J., McKown, R. L., . . . Williams, P. B. (2011). Lacritin, a Novel Human Tear Glycoprotein, Promotes Sustained Basal Tearing and Is Well Tolerated. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 52(9), 6265-6270. doi:10.1167/iovs.10-6220

Ma, P., Beck, S. L., Raab, R. W., McKown, R. L., Coffman, G. L., Utani, A., . . . Laurie, G. W. (2011). Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin (vol 174, pg 1097, 2006). JOURNAL OF CELL BIOLOGY, 192(2), 365. doi:10.1083/jcb.20051113420110107c

2010

Zhang, Y., McKown, R. L., Raab, R. W., Rapraeger, A. C., & Laurie, G. W. (2011). Focus on Molecules: Syndecan-1. EXPERIMENTAL EYE RESEARCH, 93(4), 329-330. doi:10.1016/j.exer.2010.06.008

Zhang, Y., Ryan, D. S., Bower, K. S., Ilan, N., Vlodavsky, I., & Laurie, G. W. (2010). Focus on Molecules: Heparanase. EXPERIMENTAL EYE RESEARCH, 91(4), 476-477. doi:10.1016/j.exer.2010.05.004

Hosseini, A., Samudre, S. S., Sheppard, J. D. J., McKown, R. L., Laurie, G. W., Lattanzio, F. A. J., & Williams, P. B. (2010). Lacritin, a Novel Tear Glycoprotein, is an Effective Topical Treatment in Dry Eye Animal Models. FASEB JOURNAL, 24. Retrieved from https://www.webofscience.com/