Deepa Ramesh
Pronouns: she/her
Research Mentor(s): Monique Verhaegen
Co-Presenter:
Research Mentor School/College/Department: Dermatology / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 2 – 11am – 11:50am
Room: League Ballroom
Authors: Deepa Ramesh, Jacob Arche, Dawn Wilbert, Andrzej Dlugosz, Monique Verhaegen
Presenter: 99
Abstract
Merkel Cell Carcinoma (MCC) is a rare and aggressive form of skin cancer that can be initiated by the integration of the Merkel Cell Polyomavirus (MCPyV) genome or UV DNA damage. There is a large fatality rate associated with late-stage MCC patients, and pre-clinical models are needed for studying therapeutic strategies. Recent studies in an inducible (tamoxifen + doxycycline) K5-SLAP mouse model, indicate Keratin 5-driven expression of MCPyV viral proteins small T antigen (sTAg) and truncated large T antigen (tLTAg), along with the neuroendocrine lineage driver Atoh1, in the absence of the tumor-suppressor gene p53, produces murine tumors similar to human MCCs. These mouse tumors closely mimic human MCC at the histological and transcriptomic levels and express MCC markers. However, a limitation of this current model is that tumor penetrance is low due to mouse viability issues. These mice are often in poor health and develop internal tumors prior to cutaneous MCC tumors thus requiring euthanasia, preventing this mouse model from being a truly beneficial pre-clinical model in its current state. This study examines an alternate induction protocol to drive sTAg, tLTAg and Atoh1 expression by administering topical 4-OH tamoxifen on the skin of 3-5 day old perinatal immune-deficient mice. This allows for focal recombination in the skin and evades immune surveillance of viral proteins. Early data in two separate mouse founder lines indicate that mice are fit and develop many more cutaneous tumors in a shorter time frame. Histological analysis and immunohistochemical staining indicate these tumors also resemble human MCCs. This data suggests that manipulation of the current induction strategy in the K5-SLAP mice may provide a useful mechanism to produce a healthy cohort of mice developing multiple MCC tumors for use as a future pre-clinical model.
Biomedical Sciences, Interdisciplinary
