RESEARCH

My research focuses on understanding how DNA damage and genomic instability activate innate immune signaling in cancer. Cancer cells frequently experience replication stress, chromosome missegregation, micronucleus formation, and other forms of genomic damage that can generate cytoplasmic double-stranded DNA. Although these signals should activate immune surveillance, cancer cells often suppress or redirect innate immune pathways to avoid immune recognition. Therefore, an important goal of my laboratory is to define how these pathways are altered in cancer and how they can be reactivated to restore effective antitumor immunity.

A major focus of our research is the cGAS-STING pathway, which connects cytoplasmic DNA sensing to inflammatory and type I interferon responses. When double-stranded DNA accumulates in the cytoplasm, cGAS produces cGAMP, which activates STING and downstream immune signaling. However, the presence of cytoplasmic DNA does not always result in productive pathway activation. Our laboratory investigates the molecular mechanisms that regulate cGAS trafficking, intracellular DNA transport, organelle-associated signaling, STING activation, and the overall strength and duration of the immune response.

Our recent work identified MRE11 as an important regulator of cGAS activation during tumorigenesis. Building on this work, we are now searching for additional molecules and cellular processes that control cGAS-STING signaling. We use screening-based approaches together with detailed mechanistic studies to identify regulators that determine whether damaged tumor cells activate innate immunity or escape immune control.

We are also interested in how cGAS-STING signaling interacts with autophagy, cell death, and extracellular vesicle-mediated communication. These processes may influence the transport, release, and transfer of DNA and immune-stimulatory molecules between tumor cells and immune cells. In particular, we study how tumor-derived extracellular vesicles affect macrophages and other immune populations and whether these signals promote antitumor immunity or contribute to immune suppression.

Our laboratory uses CRISPR-based screening, cancer cell models, reporter systems, live-cell imaging, molecular and biochemical assays, extracellular vesicle analysis, immune profiling, and mouse tumor models. We primarily study breast cancer while testing key mechanisms in additional tumor types. In the future, we plan to integrate organoid models, advanced imaging, computational approaches, and artificial intelligence-assisted analysis. Our long-term goal is to identify new molecular targets and therapeutic strategies that restore innate immune sensing and improve responses to radiation therapy, DNA repair-targeted therapy, and immunotherapy.