Kierra Franklin
BME PhD Proposal Presentation

Date: 2025-09-03
Time: 2:00-4:00 PM
Location / Meeting Link: HSRBII N600 https://emory.zoom.us/j/96527323692

Committee Members:
Karmella Haynes, PhD (Advisor); Tara Deans, PhD; Gabe Kwong, PhD; Felipe Quiroz, PhD; Chris Scharer, PhD


Title: Determining the Impact of MeCP2 Imbalance in T cell Epigenetic Dysregulation 

Abstract:
Systemic lupus erythematosus (SLE) is an autoimmune disease where the immune system is hyperactive and attacks a person’s own cells and tissue. SLE is a difficult disease to study, diagnose and treat because of its unpredictable symptoms and complicated underlying biology. SLE’s prevalence in women contributes to health disparities and points towards an X chromosome-linked mechanism. Moreover, SLE-associated instabilities in immune cell differentiation implicate dynamic chromatin-mediated epigenetic states as a key driver. Methyl-CpG Binding Protein 2 (MeCP2), which is expressed from the X-chromosome and broadly methylates DNA, has been validated as a genetic susceptibility locus for SLE and its overexpression induces auto-antibody production in vivo. Perturbations in DNA methylation contribute to the reorganization of other major chromatin features including histone methylation, cell signaling abnormalities, and altered cytokine production in immune cells, leading to SLE and other autoimmune diseases. In SLE, aberrant DNA methylation particularly in CD4+ T cells has been linked to disease heterogeneity and activity. It is hypothesized that SLE T cells undergo an epigenetic shift that primes them for pro-inflammatory effector response and dampens regulatory response. Although SLE tissues show altered DNA methylation and gene expression, current studies fall short of identifying precise chromatin mechanisms that drive disease and can be targeted for effective therapy. My proposal seeks to use synthetic biology tools to fill critical gaps in knowledge by (1) generating an in vitro SLE T cell model through engineered activation of the endogenous MeCP2 locus, (2) using engineered protein probes to track histone methylation in live T cells, and (3) using the proposed SLE model to determine the epigenetic consequences of MeCP2 hyper-expression. The findings from these studies will establish a link between MeCP2 and T cell dysfunction and reveal epigenetic events that precede autoimmunity.