Matilda F. Chan, M.D., Ph.D.
Assistant Professor, Departments of Ophthalmology and Anatomy
Contact Information:
513 Parnassus Ave, HSW 1301
Campus Box 0452
San Francisco, CA 94143-0452
Phone: 415-476-4758
Education:
M.D., PhD: Keck/University of Southern California
Internship: University of California, San Diego
Residency: University of Rochester
Fellowship: Cornea, Uveitis and External Disease, F.I. Proctor Foundation, UCSF
Research Interest:
The Role of Extracellular Enzymes in Regulating Corneal Repair
Corneal opacification affects millions of people and is the second leading cause of blindness in the world. Corneal injury is a major cause and can occur by a variety of mechanisms including infectious and noninfectious ulcers, incisional and laser surgery, and trauma. Regardless of the type of injury, a common set of cell-extracellular matrix (ECM) interactions mediated by growth factors, cytokines, and angiogenic factors become activated in the repair process. This normal response to injury can lead to pathologic results when corneal fibrosis and angiogenesis occur. Clinically, this can result in severe corneal opacification with vision loss and corneal transplantation may be the only option to restore functional vision.
An important need exists for the development of non-surgical strategies to prevent and treat corneal opacification. Designing specific therapeutic targets requires a thorough understanding of important factors and interactions involved in the corneal repair process. Previous studies have identified roles for various growth factors (eg. TGF-β and FGF), antiangiogenic factors (eg. angiostatin), and ECM modulating enzymes (e.g., matrix metalloproteinases). Previous and preliminary studies show that several matrix metalloproteinases (MMPs) including MMP-9 and MMP-12 and the 6-O-sulfatase Sulf-1, which are extracellular enzymes, are expressed in the cornea only upon injury implicating their possible roles in corneal repair. These enzymes are produced by epithelial, stromal and inflammatory cells and their roles in corneal repair have not been well-studied. Using cell and animal-based model systems in which these enzymes are deficient, Dr. Chan will elucidate their functions in the corneal repair process.
Representative Publications:
- Simoneau, A.R., Spruck III, C.H., Gonzalez-Zulueta, M., Gonzalgo, M.L., Chan, M.F., Tsai, Y.C., Dean, M., Steven, K., Horn, T. and Jones, P.A.: Evidence for Two Tumor Suppressor Loci Associated with Proximal Chromosome 9p to q and Distal Chromosome 9q in Bladder Cancer and the Initial Screening for GAS1 and PTC Mutations. Cancer Research 56: 5039-5043, 1996.
- Chan, M.F., Van Amerongen, R., Nijjar, T., Jones, P.A. and Laird, P.W.: Quantitative Analysis of DNA Methylation Effects on Gene Loss, Gene Silencing, and Gene Mutation. Mol Cell Biol. 21:7587-600, 2001.
- Liang, G.*, Chan, M.F.*, Tomigahara, Y., Tsai, Y.C., Gonzales, F.A., Li, E., Laird, P.W., and Jones, P.A.: Cooperativity between DNA Methyltransferases in the Maintenance Methylation of Repetitive Elements. Mol Cell Biol. 22:480-91, 2002.
- Sappington, R.M., Chan, M., and Calkins D.J.: Interleukin-6 protects retinal ganglion cells from pressure-induced death. Invest Ophthalmol Vis Sci. 47: 2932-42, 2006.
- Rutar, T., Chan M.F., Acharya N.R., and Nasari A.: Cicatrizing Conjunctivitis due to Paraneoplastic Pemphigoid. Br J Ophthalmol. 91: 1562-3, 2007.
- Chan, M.F., Sack R., Quigley R., Sathe S., Vijmasi T., Li S., Strauss, E.C., Holsclaw D., McNamara, N.A.: Protein Array Analysis of Immune and Angiogenic Modulators in Ocular Cicatricial Pemphigoid. Submitted.
Reviews and book chapters:
- Chan, M.F., Liang, G.L. and Jones, P.A.: Relationship Between Transcription and DNA Methylation. Curr Top Microbiol. Immunol. 249: 75-86, 2000.
- Chan, M.F. and Ching, S.T.: Infectious Mononucleosis (Epstein-Barr Virus). In: Roy FH, Fraunfelder FT, Fraunfelder FW, eds. Current Ocular Therapy, 6th Edition. London: Elsevier Limited; 2007.
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