Available: 01/04/21, Expires: 12/30/22
We investigate RNA mechanisms of gene expression regulation in quiescent, clinically resistant cancer cells. Tumors demonstrate heterogeneity, harboring a small subpopulation that switch from proliferation to a reversibly arrested state of quiescence that decreases their susceptibility to chemotherapy. Our data revealed that post-transcriptional mechanisms are altered by stress signaling in such quiescent, drug resistant cells in leukemias. Conventional post-transcriptional mechanisms are reduced, with modification of RNAs, associated complexes & ribosomes that enable specialized gene expression.
The primary goal of our research is to characterize the specialized gene expression program in quiescent drug resistant cells in cancers, & the RNA mechanisms that contribute to tumor persistence, using in vitro & in vivo systems.
We will comprehensively characterize the altered post-transcriptional & translational gene expression in drug resistant cancers. This will yield insights into the differences that underlie clinical resistance & tumor survival & can lead to new therapeutic options.We will elucidate the regulation of RNAs & ribosomes, by G0- & therapy-induced DNA damage & stress signaling that we have observed to alter post-transcriptional mechanisms in drug resistant cells. This will shed light on drug survival adaptations that operate via RNA mechanism changes in cancers.We will utilize our findings to develop therapeutic applications that interfere with RNA mechanisms that drive key regulators in resistant cancer. These will impair unique RNA mechanisms in persister cancer cells without affecting normal cells, to curb expression of survival regulators & curtail tumor persistence.
Projects available for students with either molecular biology, cell culture, cancer biology, informatics, or related experience, interested in translating basic studies into therapeutic avenues & committed to research.