My research

 

I have a long-standing interest in understanding the mechanisms of epithelial regeneration as it pertains to tissue engineering, wound repair, and neoplasia. My work has thematically been focused on engineering state-of-the-art technologies to closely investigate how distinct epithelial cells coordinate during tissue development and cancer progression. My doctoral research established the 3D skin spheroid plasticity assay, a high throughput cell culture method for patterning epithelial regenerative plasticity ex vivo (Stem Cell Res 49:102048). Using this system, I helped determine the role of epidermal stem cells in HPV-driven neoplasia (J Virol 92:e00331-18), outlining the phenotypic and transcriptional stem cell states of primary neonatal keratinocyte lines established from different human neonatal skin donors. I equally investigated immortalization responses across various stem/progenitor-like keratinocyte populations purified from these tissues and established that basal stem-like keratinocyte populations were considerably more susceptible to pre-neoplastic transformation by HPV16 DNA than autologous committed progenitors and terminally differentiated cells. These findings depicted the stem-cell status of primary human keratinocytes as a foremost phenotypic determinant of transformation responses to oncogenic HPV16 DNA. Currently, my postdoctoral research focuses on defining the epigenetic regulators of epithelial-immune crosstalk, as this represents a central node of many epithelial diseases and conditions. Through the use of transgenic mouse models and innovative lineage-specific gene editing systems, my studies have identified putative chromatin modifiers with targeted activities in keratinocyte regeneration and neoplasia. Through this work, I hope to elucidate the fundamental requirements for tissue regeneration and cancers, and to develop targeted therapeutic approaches for these malignancies. The breath of these studies has provided me with extensive training in tissue engineering, stem cell biology and in vivo tissue gene editing. Following my fellowship, I hope to lead an independent research program exploring the molecular, epigenetic, and genetic modulators of epithelial renewal and maintenance.

ywoappi [at] gmail [dot] com