The biology of microRNAs and their dysregulation in cancers
We use classical biochemical strategies and new experimental approaches to identify and characterize microRNAs (miRNAs) in primary and transformed lymphocytes. Our description of the first cell-free miRNA-directed translational repression reactions defined one mechanism used by miRNAs to repress translation initiation. In studies of chronic lymphocytic leukemia (CLL), thought to be a disease of resting lymphocytes, we demonstrated the B cell activation status for CLL using miRNA expression profiling of highly-enriched CLL cells. These findings suggest that changes in individual miRNAs may predict clinical course in CLL. We currently investigate the contribution of miRNAs in ribosomopathies, including Diamond Blackfan Anemia and Shwachman Diamond Syndrome, using innovative genomic approaches in patient-derived iPS cells. Using miRNA expression profiling of non-syndromic cancers, new insight into the molecular pathogenesis of several cancers, particularly the leukemias and melanoma, have been revealed.
Recent studies have shown the contribution of the intronic miRNA, miR-211, in tumor suppression and regulation of the melanoma metastasis network, highlighting its therapeutic potential. Current studies involve a comprehensive pathway mapping in melanoma circulating tumor cells, a rare and intractable population of cancer cells that have been associated with poor prognosis.
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