- Epigenetic mechanisms of epidermal stem cell self-renewal and differentiation
- Transcription factor regulation of epidermal differentiation and proliferation
- Gene regulatory mechanisms in tumorigenesis
Dr. George Sen’s research has been focused on understanding the molecular mechanisms of epidermal stem cell self-renewal and differentiation. Understanding the factors that govern this process is extremely important as perturbations in this intricate balance between growth and differentiation can lead to a variety of human skin disorders. Increased proliferation and diminished differentiation can lead to hyperproliferative disorders such as psoriasis, basal or squamous cell carcinomas. Thus, a comprehensive understanding of the regulators of epidermal stem cell self-renewal and differentiation would be key to unlocking the molecular mechanisms underlying skin disorders and the possibility of developing better treatment for these debilitating disorders. Dr. Sen has focused on identifying epigenetic factors that have functional roles in promoting epidermal stem cell self-renewal and differentiation. His group has recently demonstrated that both regulators of H3K27me3 and DNA methylation play vital roles in epidermal stem cell self-renewal and differentiation. They demonstrated that epigenetic factors such as EZH2 and SUZ12, which mediate H3K27 trimethylation and DNA methylation enzymes such as DNMT1 are necessary for promoting adult stem cell self-renewal. Loss of these factors led to spontaneous differentiation of the interfollicular epidermis. Dr. Sen’s research in the future will continue to focus on identifying and characterizing novel regulators of epidermal homeostasis. Their ultimate goal is to define all the regulators that are important for stem cell self-renewal, differentiation, and tumorigenesis.