The HCEMM-SU Translational Dermatology Research Group focuses on understanding the biology of pigment producing cells (melanocytes) and melanoma cells.
The group focuses on three different aspects of melanocyte and melanoma biology: mechanism of pigmentation, regulators of cell death in melanoma and overcoming resistance to targeted and immunotherapies in melanoma.
Although pigmentation is a well-characterized physiological process that can be triggered by UV radiation, the group is actively seeking to identify and develop novel pharmacologic approaches to modify pigmentation. The overall goal of these studies is to minimize DNA damage induced by UV radiation by fine-tuning pigmentation independently of UV radiation.
Targeted and immunotherapies have revolutionized the management of metastatic melanoma in the last decade, however resistance to these modern therapies still develops in most patients. The recently discovered ferroptosis, an iron-dependent, lipid-peroxidation mediated cell death has been implicated to be effective in certain subsets of melanoma. Therefore, the group aims to understand and promote ferroptotic cell death in melanoma by identifying regulators of ferroptotic cell death using in vitro CRISPR-cas9 screens.
Despite recent developments in the field of immunooncology by the introduction of immune-checkpoint blockade (ICB) in the management of melanoma, resistance to ICB therapies still poses a tremendous problem. The group aims to identify novel therapeutic approaches to overcome resistance to ICB therapies. The most common resistance mechanism, the loss of antigen presentation, might offer novel vulnerabilities to antigen presentation-independent mechanisms. The group aims to find regulators and novel therapeutic targets by creating a novel mouse model of immunotherapy resistance. This novel model of ICB resistance combined with in vivo genome-wide CRISPR screen approaches will be used to identify novel targets that may be utilized to overcome ICB resistance. This project may provide a better mechanistic understanding of melanoma-immune cell interactions and offers immediate translational relevance from bench to the bedside.