Metastasis, the spread of cancer cells from a primary tumor to distal organs, accounts for the overwhelming majority of human deaths from cancer. The Tavazoie laboratory employs a systems biology approach that integrates molecular, cellular, animal, and clinical observations to discover and characterize key molecular regulators of metastasis, with the goal of developing clinically viable therapies for its prevention and treatment.
This year, over eight million people will die from cancer globally. For most, the cause of death will be metastatic colonization of distant organs by cancer cells. As is the case with normal development, metastatic progression requires the proper expression of effector genes that drive specific cellular phenotypes. Tavazoie is a cancer biologist and medical oncologist interested in how such pro-metastatic gene expression programs are established in cancer cells, how they enable cancer cells to metastasize, and how such programs emerge during cancer progression.
The Tavazoie laboratory employs molecular, biochemical, genetic, imaging, clinical association, and computational approaches to study this process. These insights generate an integrated molecular and biological model of metastasis formation and progression. This systematic approach has revealed that the acquisition of the metastatic phenotype by breast cancer cells requires modulation of specific small noncoding RNAs (microRNAs), which leads to the altered expression of downstream genes that regulate metastasis formation. Tavazoie’s lab has shown this to be the case not only in breast cancer, but also in other prevalent cancers such as melanoma and colorectal cancer, where tissue-specific microRNAs govern metastasis formation. The expression levels of these metastasis-regulating microRNAs and their target genes in human cancer specimens support their functionally implicated roles in cancer.
The Tavazoie lab is using these microRNAs as molecular probes to efficiently uncover their cellular phenotypes and to implicate their downstream target genes and pathways—establishing signaling pathways that govern metastasis. The lab has developed mouse metastasis systems that model the progression of prevalent human cancers, such as triple negative breast cancer, melanoma, colorectal cancer, and pancreatic cancer. These diseases were chosen because of their large impact globally and the need for effective targeted therapies. To ensure the generality of their conclusions, Tavazoie’s lab uses patient-derived xenograft, fully immunocompetent, and genetically initiated mouse models.
These studies of human disease have led the lab to discover additional noncoding RNAs, such as specific tRNAs and tRNA-derived fragments, as regulators of cancer progression and metastasis. By using cancer as a model system, the Tavazoie lab has uncovered the basic mechanisms by which these other noncoding RNAs regulate gene expression posttranscriptionally. These studies are revealing surprising modes of gene expression regulation that extend to normal cells and could open new avenues for therapeutic interventions in cancer and beyond.