Our research team has a long-standing interest in understanding the molecular and cellular basis of non-melanoma skin cancer. This work is based heavily on the development and characterization of novel mouse models of disease, complemented by analysis of human tissue samples and cell lines. Our current work addresses two types of non-melanoma skin cancer: basal cell carcinoma (BCC), the most common form of skin cancer; and Merkel cell carcinoma (MCC), a rare but highly aggressive form of skin cancer, linked in many cases to a viral infection.
Our BCC research centers upon defining the roles of deregulated activation of the Hedgehog pathway, and interacting signaling pathways, in BCC initiation and expansion; mechanisms underlying tumor heterogeneity; and the impact of aging on BCC development and treatment response. Additional work is focused on understanding the functions of Hedgehog signaling in hair follicles and taste buds.
Our MCC studies are dissecting the viral pathogenesis of this rare and deadly skin cancer. We identified a single Merkel cell polyomavirus protein as sufficient to drive tumor development in genetically-engineered mice and used this protein to generate the first mouse model of MCC, providing novel insight into the initial steps in MCC development.
- Merkel Cell Polyomavirus T Antigens In Tumorigenesis (NIH/NCI 5R01CA189352; PI: Dlugosz)
- Molecular and Cellular Basis of Polyomarvirus-Associated Hair Follicle Dysplasia (NIH/NIAMS 1R21AR072284-01A1 PI: Dlugosz)
- Probing The Role of Aging in Basal Cell Carcinoma Development and Treatment Response (NIH/NCI 5UH2CA213386; PI: Dlugosz)
- Hedgehog Signaling in Maintaining Taste Organ Structure and Function: Basic and Clinical Studies (NIH/NIDCD 5R01DC014428-04 Multi-PI: Allen/Bradley/Dlugosz/Mistretta)