The Sen Lab is interested in understanding the molecular mechanisms governing stem cell self-renewal, differentiation, and progression to neoplasia. We use human epithelial tissue as a model system because of the ability to regenerate the organ on immune deficient mice. Mammalian epidermis is a stratified epithelium that resides on top of a layer of extracellular matrix, which separates it from the underlying dermis. This self-renewing tissue has a turnover rate of approximately 4 weeks in humans. The self-renewal capability of the epidermis is the result of epidermal stem cells that reside in the basal layer of the epidermis. As the stem cells differentiate, they withdraw from the cell cycle and detach from the basement membrane and migrate upwards to form the differentiated layers of the skin, which include the spinous layer, granular layer, and the stratum corneum. Perturbations in the proliferative and differentiation capacity of the stem cells result in human diseases such as cancer.
To determine the functional significance of genes of interest, we use a new genetic model named Multi-Functional Human Tissue Genetics (MFG), which allows us to alter the function of up to 10 alleles at once all in the context of 3 dimensionally intact human skin within architecturally faithful mesenchymal tissue.