Research Summary:

During development, the initially single-layered epithelium of the presumptive skin requires precise coordination of cell proliferation and differentiation to execute epidermal stratification. Defects in the timing of these events can lead to congenital anomalies such as ichthyosis and epidermolysis bullosa. Epigenetic regulation is emerging as an important modulator of keratinocyte differentiation during development. In particular, Protein Arginine Methyl Transferase 5 (PRMT5) has been identified as necessary for preventing differentiation of keratinocytes in vitro and for maintaining a progenitor, stem-cell fate in both germ-cell and limb development in vivo. To investigate the role of PRMT5 during epithelial development, we have developed a conditional mouse model in which Prmt5 is deleted from the early ectoderm, which gives rise to the skin. Epithelial loss of PRMT5 resulted in gross skin defects, reduced skin barrier function, and reduced postnatal viability. Histological analyses revealed severe defects in epidermal stratification, including major reduction of the proliferative basal layer. As PRMT5 is known to catalyze the methylation of arginine residues in critical proteins, including histones, leading to genome-wide accessibility changes, we performed single-cell RNA and ATAC-seq on mutant back skin. Our analysis suggests that PRMT5 does in fact not exhibit histone remodeling activity in this context, but its loss instead results in the emergence of an atypical keratinocyte-like cell population not found in control conditions. Ongoing research in out lab aims to further characterize this atypical keratinocyte population and its impact on epidermal development.

Honors & Awards:

College of Dentistry NIH T90 Pre-doctoral Fellowship (2023 - 2024)

Genetics T-32 Pre-doctoral Training Grant (2020 - 2021)