Laurie Laboratory

UVa Cell Biology


    Our focus is on the epithelial-specific prosecretory mitogen ‘lacritin’.  We discovered lacritin out of a screen for factors capable of stimulating tear protein secretion by lacrimal acinar cells (Sanghi et al, '01).  Lacritin retains this function even when cells are stressed with inflammatory cytokines (Fujii et al, ‘13).  When added topically to dry eye mice (Vijmasi et al, 14) (Wang et al, ’15) or normal rabbit (Samudre et al, ‘11) eyes, lacritin stimulates basal tearing.   Surprisingly, lacritin is a tear and salivary protein.  Lacritin is multifunctional (Karnati et al, ‘13). It restores health to stressed corneal epithelial cells (Wang et al, ’13), (Karnati et al, ’16) or eyes (Vijmasi et al, 14), and promotes corneal wound healing (Wang et al, ’14).  C-terminal cleavage releases C-terminal bactericidal fragments (McKown et al, ’14), (Azkargorta et al, ‘15).  Tissue transglutaminase in tears crosslinks lacritin into dimers, trimers and larger polymers.  Only lacritin monomers are fully active.  Lacritin monomer is selectively downregulated in dry eye disease, the most common eye disease (Karnati et al, ‘13).  Since topical lacritin successfully treats dry eye in two different mouse models, a lacritin-derived drug ‘LacripepTM’ is soon to enter a 201 patient phase I/II trial in primary Sjogren’s sydrome dry eye.  The ‘Lacritin and Dry Eye’ Facebook page documents progress.  Check out the lacritin Wikipedia page.  Check out trial sites.

    Understanding the fascinating ways by which lacritin works is the collective effort of the ‘Lacritin Consortium’, that has met yearly since 2002.  The over 60 different lacritin and other cDNA constructs developed by collaborators at James Madison University were, for example, essential in working out cell targeting (Ma et al, ‘06), (Zhang et al, ’13) and signaling mechanisms (Wang et al, ’06), (Wang et al, ’13).  A number of these constructs are available via Addgene.  The ‘Lacritin Chronology’ is pictured below.



Lacritin in epithelial cell biology and ‘dry eye’

Eye Tearing

Epithelial Secretion

Epithelial Cytoprotection

Epithelial Renewal

Epithelial Wound Healing

Cleavage Dependent Bactericide

Gordon Laurie, PhD

Karina Teixeira, PhD

Mohammad Sharifian, PhD (9.1.18)

Xavier Horton, BS

Margaret Ryan, MS

Jeff Romano, BS

Tuyet-Minh Tran