Timothy Blalock, Ph.D. Schepens Eye Research Institute 20 Staniford Street Boston MA 02114 E-Mail: blalock@vision.eri.harvard.edu 617-912-0299 Sponsor Ilene Gipson, Ph.D. gipson@vision.eri.harvard.edu

"I am honored to be a part of the Molecular Bases of Eye Disease postdoctoral training program at Harvard Medical School. It is such a great opportunity for me to perform ophthalmology research at an institute surrounded by so many eminent experts in the field. The program allows postdoctoral fellows to collaborate with scientists with a broad range of backgrounds to increase the exposure of new techniques and ideas in vision science."

The goal of my research is to elucidate the roles of mucins, a class of high-molecular weight heavily o-glycosylated proteins, that are expressed on apical surfaces of wet-surfaced epithelia. Suggested functions of the mucin family include lubrication of surfaces and protection from epithelial desiccation and pathogens. All mucins have tandem repeats of amino acids rich in serine and threonine in the protein backbone, which serve as sites for O-glycosylation. Up to 18 mucins have been characterized thus far through molecular cloning and sequencing with each having unique numbers of amino acids in their tandem repeats. Both secreted and membrane-associated mucins have been shown to be expressed by the ocular surface epithelia. Three membrane-associated mucins (MUC1, MUC4, and MUC16) are expressed by both corneal and conjunctival epithelia. Each of these mucins has a varied extracellular domain structure as well as a cytoplasmic tail which may include EGF-like domains (MUC1), SEA domains (MUC16) or potential signaling sites (MUC4). It is not known whether these variations in mucin sequence and structure impart unique functions on the ocular surface. They may function together as an ocular surface barrier or they may have individual signaling functions important in epithelial cell biology.
We hypothesize that each of the membrane-associated mucins expressed on the ocular surface have unique functions. Constructs are being produced expressing labels on the extracellular and intracellular domains of the membrane-anchored mucins. The functions of the mucins will be assessed using extracellular domain shedding and cell-cell adhesion assays in addition to visualization of cellular localization and processing. This will allow further characterization of mucin alteration in disease and lead to an understanding of their regulation in epithelial cells.

Publications

TD Blalock, R Yuan, AS Lewin, GS Schultz. (2003) Ablation of CTGF mRNA using hammerhead ribozymes blocks TGF-b-mediated cell proliferation. Exp. Eye Res. 2004, in press.

Q Garrett, TD Blalock, GS Schultz, JT Daniels, PT Khaw. CTGF is involved in TGF-b1-stimulation of myofibroblast differentiation and collagen matrix contraction in the presence of mechanical stress. Invest. Ophthalmol. Vis Sci. 2004, in press.

WD Esson, A Neelakantan, S Iyer, TD Blalock, GS Schultz, MB Sherwood. The roles of CTGF and TGF-b in improved outcomes of blebs following glaucoma filtering surgeries. Invest. Ophthalmol. Vis. Sci. 2004;45(2):485-491.

FJ Ollivier, DE Brooks, GS Schultz, TD Blalock, SE Andrew, AM Komaromy, TJ Cutler, ME Lassaline, ME Kallberg, GB Van Setten. Connective tissue growth factor in tear film of the horse: Detection, identification and origin. Graefe's Arch. Clin. Exp. Ophthalmol. 2003;241(11):1103-9.

KC Flanders, CD Major, A Arabshahi, EE Aburime, MH Okada, M Fujii, TD Blalock, GS Schultz, A Sowers, MA Anzano, JB Mitchell, A Russo, AB Roberts. Interference with TGF-b/Smad3 signaling results in accelerated healing of wounds in previously irradiated skin. Am. J. Pathol. 2003;163(6):2247-2257.

JT Daniels, GS Schultz, TD Blalock, Q Garrett, GR Grotendorst, NM Dean, PT Khaw. Mediation of TGFb1- stimulated matrix contraction by fibroblasts: a role for CTGF in contractile scarring. Am. J. Pathol. 2003;163(5):2043-2052.

FJ Ollivier, DE Brooks, ME Kallberg, AM Komaromy, ME Lassaline, SE Andrew, KN Gelatt, GR Stevens, TD Blalock, GB van Setten, GS Schultz. Evaluation of various compounds to inhibit activity of matrix metalloproteinases in the tear film of horses with ulcerative keratitis. Am. J. Vet. Res. 2003;64(9):1081-1087.

TD Blalock, MR Duncan, JC Varela, MH Goldstein, SS Tuli, GR Grotendorst, GS Schultz. Connective tissue growth factor expression and action in human corneal fibroblasts and in rat corneas following phototherapeutic keratectomy. Invest. Ophthalmol. Vis. Sci. 2003;44(5):1879-1887.

GB van Setten, TD Blalock, GS Schultz. Connective tissue growth factor in human anterior chamber fluid — Possible contribution to glaucoma and intraocular wound healing. Acta Ophthalmol. Scand. 2003;81(1):51-53.

MK Mazaheri, GS Schultz, TD Blalock, HH Caffee, GA Chin. Role of CTGF in breast implant elastomer capsular formation. Ann. Plast. Surg. 2003;50(3):263-268.

GB van Setten, M Aspiotis, TD Blalock, GR Grotendorst, GS Schultz. Connective tissue growth factor in pterygium: simultaneous presence with vascular endothelial growth factor — Possible contributing factor to conjunctival scarring. Graefe's Arch. Clin. Exp. Ophthalmol. 2003;241(2):135-139.

GB van Setten, TD Blalock, GR Grotendorst, GS Schultz. Detection of connective tissue growth factor in human aqueous humor. Ophthalmic Res. 2002;34(5): 306-308.

TD Blalock, JC Varela, S Gowda, Y Tang, C Chen, BA Mast, GS Schultz. Ischemic skin wound healing models in rats. Wounds. 2001;13(1):35-44.

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Last updated: February 23, 2004