Epigenetic and chromatin-based regulation of DNA repair and genome maintenance pathways. The SNF2 family chromatin remodeler HELLS (SMARCA6, LSH) is a poorly understood chromatin-associated protein, which has emerged as an important regulator of genome stability and cancer pathways. Our work aims to establish a new paradigm in chromatin-based regulation of DNA alkylation repair and to reveal and characterize new pathways and mechanisms of HELLS-mediated genome maintenance relevant to cancer prevention and treatment.
Regulatory interplay between DNA damage response and immune responses. Proficient and tightly regulated DNA damage response (DDR) and immune responses are the two most critical tumor suppressor systems preventing cancer development. The regulatory interplay between solar UV-induced DNA damage responses and immune responses is poorly understood in the context of skin photocarcinogenesis. We aim to identify new regulators of Nucleotide Excision Repair (NER) and determine contribution of UV-induced DNA damage to immune responses.
Development of new assays and methodologies enabling quantification and genome-wide mapping of mutagenic alkyl DNA adducts. DNA alkylation damage commonly induced by chemotherapeutics, inflammation and environmental carcinogens plays an important role in cancer development and treatment. It is imperative to be able to systematically examine genome-wide profiles of these lesions and investigate how factors (such as modifications of chemotherapy agents, or the genomic and epigenomic landscape of the cell) influence initial adduct formation and repair. To this end, we are developing NGS sequencing methods enabling genome-wide mapping of DNA alkylation.
