Projects
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METASTASIS BIOLOGY & GENETICS
We have identified critical genes that regulate metastasis formation in common cancers. We seek to understand the molecular and cellular mechanisms by which these genes regulate metastasis formation within the metastatic niche. We have also uncovered the first evidence for a hereditary genetic basis of human metastasis. We are employing powerful molecular, genetic, biochemical, pharmacological, imaging, and clinical association approaches to discover additional heritable genes underlying cancer metastasis and to understand their mechanisms of action.
METASTASIS THERAPY
Our discovery of critical genes that regulate metastasis formation has unveiled new therapeutic paths. We are developing small-molecule and antibody-based therapeutics as a means of preventing and eradicating metastatic disease. We have advanced these approaches into human clinical testing with our collaborators at the biotechnology company Inspirna, where proof-of-concept for two of these therapies has been observed in advanced stage and refractory cancers. We are working towards developing anti-metastatic combination regimens that will be curative.
TRNA-MEDIATED GENE REGULATION IN CANCER
We have found that as cancers become metastatic, specific tRNAs become modulated. This is surprising, since tRNAs are thought to be static adaptor molecules. Such tRNA modulations enable enhanced translation of pro-metastatic genes. We are employing molecular, genetic, and biochemical approaches to understand the basic mechanisms by which this non-canonical gene regulatory mechanism operates.
GENE REGULATION BY TRNA-DERIVED FRAGMENTS IN HEALTH AND IN CANCER
tRNAs have been observed to undergo cleavage across species upon exposure of cells to stress. We have observed that specific tRNAs become fragmented--generating small trans-acting tRNA fragments that regulate gene expression via interactions with RNA binding proteins. We are studying the mechanisms of generation and action of such stress-induced tRFs in nematode, mouse, and human cells. By understanding this process, we aim to exploit tRNA-fragmentation as an anti-cancer therapy.