Research
Metastasis, or the spread of cancer from a primary tumor to a distal organ, is the primary cause of cancer death. Despite this fact, the molecular mechanisms and fascinating biology underlying metastatic progression are poorly understood. Scientists in our lab are discovering the critical genes and cellular processes that drive this process and have provided the first evidence for a role of hereditary genetics in human metastasis formation. We are applying this understanding towards development of the next generation of cancer therapeutics that selectively target metastatic disease. An exciting emergent area of study is our uncovering of a major role for the nervous system in regulating cancer metastasis. By studying how cancer cells turn genes on and off during metastasis, our scientists have also uncovered new mechanisms of gene regulation mediated by transfer RNAs. We employ a broad range of approaches and technologies, including many we have developed to aid our studies. Our overarching goals are to understand metastasis biology as a means of developing curative anti-metastatic therapies and to train future leaders in biomedical research.
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. We are also studying how our diet can impact such tRNA modulation and thus impact gene regulation to elicit disease. These studies are illuminating unexpected novel approaches for gene expression control.
REGULATION OF CANCER METASTASIS BY THE CENTRAL NERVOUS SYSTEM
We have found that during breast cancer metastasis, primary breast cancers become increasingly innervated by sensory neurons. We have further found that breast cancer cells enhance the activity of such neurons, leading to the increased release of sensory neuropeptides that act on cancer cells to drive invasiveness and metastatic growth. We are studying how cancer cells activate sensory neurons, how sensory neuropeptides elicit metastatic gene expression programs, and how such neuro-cancer interactions evolve in the progression of distinct cancer types.