Leon Hess Associate Professor
Elizabeth and Vincent Meyer Laboratory of Systems Cancer Biology
The Rockefeller University
We have discovered a large number of genes and multiple pathways and novel cellular processes that regulate cancer progression. We have also discovered novel modes of gene expression regulation involving post-transcriptional processes.
We would like to discover regulatory networks that promote metastatic progression of prevalent cancer types and to understand our basic mechanistic understanding of gene expression regulation by small non-coding RNAs.
Discovery, Characterization, and Genetic Modeling of tRNA-derived Fragments that Promote Cancer Progression
The vast majority of deaths from most cancers are caused by the metastatic spread of malignant cells from the breast to other organs such as the lung, bones, liver, and brain. In order for cancer cells to metastasize, certain genes must be turned on and others turned off. Within every one of our cells there exist a class of RNAs called tRNAs. We have found that in cancer cells, specific tRNAs can be fragmented into small pieces called tRNA fragments. Moreover, these pieces of RNA can turn genes off within our cells. We have discovered that breast cancer cells that metastasize have high levels of one such tRNA fragment.
“It is an honor that our basic work in understanding the molecular mechanisms underlying cancer progression and gene-expression regulation were recognized by the prize committee. The support provided by the Pershing Sohn award will enable us to push forward into unchartered territory that conventional low-risk funding mechanisms shy away from.”
We wish to determine what this fragment does in cancer cells, to identify which genes it regulates, and how it regulates such genes. Moreover, we wish to determine if blocking this tRNA fragment could block cancer metastasis. We will also determine if mice that are engineered to express higher levels of this tRNA fragment develop more metastatic disease. These studies could provide insights into how genes are turned on and off in cancer and in normal cells and lead to the development of novel cancer therapies aimed at a previously uncharacterized molecular process.
“Doing work that others believe is unusual, surprising, and outside the mainstream. It means using novel tools and charting into areas others have not broached. It means discovering basic and applied knowledge not uncovered before. It means taking major risks and having conviction.”