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We are studying basic cellular and molecular mechanisms that regulate tissue stem cell activity, focusing on adult epithelial stem cells in the skin. Using genetic and genomic approaches in mouse skin and comparing with human skin, we are mapping the organization and regulation of hair follicle and epidermal stem cells and their interaction with the microenvironment or ‘niche’. We are analyzing genetic control of stem cell activation, self-renewal, and differentiation. Our general focus is on stem cell fate choice by epigenetic regulation, transcription regulation via specific developmental transcription factors and RNA Pol II Pausing mechanisms, and chromatin modifying factors. We are particularly fascinated by the role of epithelial stem cells in organizing cells in their surrounding environment, such as melanocytes, blood vessels, nerves, fat cells, and fibroblast. Additionally, we explore how our findings in mice might apply to normal and diseased human skin.