David M. Owens, PhD

The overall aim of the research in my laboratory is to define the contributions of stem cells and differentiated cells to normal skin function and neoplastic growth. The epidermis of skin is a multilayered stratified epithelium comprised of a single basal layer of dividing cells that give rise to non-dividing progeny that traverse the upper epidermal layers and terminally differentiate. The epidermis is known to contain reservoirs of multipotent stem cells, which are likely candidates for cells of origin for skin tumors based on their highly proliferative nature and capacity for self-renewal. The accessibility of epithelial stem cell populations in the skin, coupled with a vast arsenal of well-characterized experimental skin cancer models, renders the skin as an ideal tissue for my laboratory to investigate the role of stem cells in epithelial cancer.

To maintain skin homeostasis, epidermal cells must establish extensive communication networks with each other as well as neighboring cell types including melanocytes, mesenchymal cells and various leukocyte lineages. This highly complex communication network, collectively termed the microenvironment, integrates both extracellular and intercellular signals, and regulates the balance between epithelial cell proliferation and differentiation. Over the last few years, my laboratory has made significant inroads in understanding cell-cell communication between differentiated infiltrating cells in the dermis and dividing cells in the basal epidermal layer, and how perturbations in this communication can stimulate the development of skin diseases such as cancer. Along these lines, my laboratory has focused on three main areas of skin biology: i) touch, ii) stem cells, and iii) cancer. We made significant contributions in these areas by our fundamental discoveries of two novel stem cell niches, this isthmus and touch dome, as well as important new insights into the pathogenesis of epithelial cancers with a focus on infiltrating immune lineages. In addition, we are actively investigating the role of the tumor microenvironment including the CD200-CD200R signaling axis in tumor-infiltrating myeloid lineages and the role of Tbc1d10c as an intrinsic suppressor of CD8 T cell activation and cytotoxic effector function.