Welcome to the Chen Lab
Research Statement
My research has successfully identified a molecular mechanism that may play a role in maintaining ocular immune privilege, and provides a gene-based explanation for the exceptionally high success rate of corneal transplants in low risk patients without donor-typing and matching.
Based on strong evidence that DNA methylation occurs in tumor cells when they are introduced into the eye, I hypothesized that the ocular environment induces epigenetic methylation, which downregulates gene expression in foreign tissues within the eye and mitigates destructive inflammatory ocular immune responses. My research addresses: (i) Identification of methyltransferases upregulated by ocular environment responsible for gene methylation, using microarray analysis, real-time PCR, and Western blot analysis, ii) Determining whether methylation initiated by the ocular environment regulates gene expression by specifically methylating individual genes or by inducing global methylation and chromatin remodeling, using promoter-reporter vector assays, methylation specific PCR and chromatin immunoprecipitation techniques, and (iii) Isolation and identification of the factor(s)in the ocular environment responsible for triggering epigenetic gene regulation, using protein fractionation, mass spectroscopy, and proteome analysis. A better understanding of how the eye utilizes the molecular mechanisms of epigenetic regulation to maintain ocular immune privilege and prevent destructive innate and adaptive immune responses that threaten the survival of transplanted corneal tissue will provide the basis for development of new gene regulation-based strategies to improve chances of successful corneal transplants in high-risk patients whose prognosis for accepting a transplant are extremely poor due to persistent corneal inflammation.
