Our laboratory employs an interdisciplinary approach combining cell biology, biochemistry, as well as mouse and computational models to dissect the contributions of chromosomal instability (CIN) toward three key processes in human cancer: therapeutic resistance, immune evasion, and metastasis.
The role of CIN in cancer metastasis
CIN and the tumor microenvironment
The ability of CIN to promote chronic inflammatory signaling highlights the intimate crosstalk between the cancer genome and the tumor microenvironment. How chromosomally unstable tumor cells not only survive, but thrive and metastasize, amidst chronic inflammation remains a mystery. We are interested in dissecting tumor-intrinsic and extrinsic mechanisms that enable cancer cells to tolerate and co-opt chronic inflammatory signaling to acquire metastatic and drug-resistant traits. Such an understanding would pave the way for strategies that aim to exploit CIN-induced inflammation as a therapeutic vulnerability.
The cellular biology of cytosolic DNA
Ongoing errors in chromosome segregation present cancer cells with a unique challenge, namely the presence of genomic double-stranded DNA in the cytoplasm, where it does not naturally belong. Beyond the ensuing inflammatory signaling, how cancer cells process cytosolic DNA is not understood. Using biochemical and cellular tools, including super-resolution microscopy, we are interested in interrogating key pathways involved in the generation and processing of cytosolic DNA and their impact on genomic instability and cellular metabolism.