Heads of Laboratories
Metastasis, the spread of cancer cells from a primary tumor to distal organs, accounts for the overwhelming majority of human deaths from solid cancers. Dr. Tavazoie’s laboratory employs a systems biological approach that integrates molecular, cellular, animal and clinical observations to identify and characterize key molecular regulators of this complex process, with the ultimate goal of developing novel therapies aimed at its prevention and treatment.
Cancer metastasis is a complex program wherein cancer cells escape the primary tumor site, enter the circulation, attach to the vascular bed at the target organ site, extrude through narrow endothelial junctions and colonize the parenchymal tissue of the target organ. This seemingly insurmountable and inefficient multistep program is responsible for the vast majority of cancer deaths. Despite its vast clinical importance and inherently fascinating underlying biology, the metastatic cascade is poorly understood — both at the molecular level and at the cellular and tissue microenvironment levels. To dissect the mechanistic basis of metastatic progression, the Tavazoie lab uses a multidisciplinary approach employing molecular, biochemical, genetic, imaging, computational and clinical association methods to characterize the critical regulatory pathways that mediate the distinct stages of this process.
To better understand the metastatic program, Dr. Tavazoie and colleagues established an in vivo model of breast cancer metastasis in mice in which human cancer cell lines and primary cancer cells obtained from patients reproducibly metastasize to bone and lung. Using this model, researchers identified genes that promote metastasis. During efforts aimed at identifying regulatory mechanisms that establish such metastatic gene expression states, Dr. Tavazoie discovered the first noncoding RNAs (microRNAs) that suppress metastasis. He and colleagues further showed that one of these microRNAs, microRNA-335, regulates metastasis and migration of cancer cells by suppressing the expression of the transcription factor SOX4 and the extracellular matrix protein Tenascin C. This work identified microRNAs as robust regulators of metastasis through their coordinate suppression of multiple novel prometastatic target genes involved in common processes.
The identification of these and other metastasis regulatory microRNAs is of clinical value since the expression levels of these molecules in primary tumors was shown by Dr. Tavazoie to predict the likelihood of future metastatic relapse. Additionally, the identification of the pathways that regulate these microRNAs as well as the downstream genes that the microRNAs themselves regulate will reveal attractive targets for therapeutic intervention. Dr. Tavazoie’s lab has identified metastasis-regulating microRNAs and their signaling networks in melanoma and colorectal cancer, two prevalent disease entities with high propensities for metastasis. The mechanistic dissection of these networks will allow for a comparative analysis of key regulatory pathways employed by cancer cells arising from distinct tissues — such as the breast, colon or skin — as they metastasize to common target organs such as the liver or lung. It will also allow clinicians to identify patients who are at highest risk for future metastatic relapse of colon cancer so that more aggressive and experimental therapies can be offered to them.
Another focus of the Tavazoie lab is to identify and characterize the roles of molecules that enable single cancer cells to grow and colonize distal organs. The ability of single cancer cells to generate an entire tumor at distal sites is similar to the capacity of stem cells to repopulate tissues and as such may provide interesting insights into commonalities in mechanisms and molecular pathways employed by these distinct cell types in these different biological processes.
The overarching translational goals of the Tavazoie lab are to identify and therapeutically target critical nodes required for the progression and metastasis of prevalent human cancers.
Dr. Tavazoie received his undergraduate degree from the University of California, Berkeley, his Ph.D. from Harvard University and his M.D. from Harvard Medical School and the Harvard-MIT Division of Health Sciences and Technology. Following a residency and internship in internal medicine at Brigham and Women’s Hospital/Harvard Medical School, he joined Memorial Sloan-Kettering Cancer Center as a clinical fellow in 2005 and became a research fellow in medical oncology in 2006. He joined Rockefeller as an assistant professor in 2009.
In 2009 Dr. Tavazoie was the recipient of the National Institutes of Health New Innovator Award and a combined American Society of Clinical Oncology and American Association for Cancer Research Young Investigator Award. He was also named a Rita Allen Foundation Scholar, a Sidney Kimmel Foundation for Cancer Research Scholar and a Sinsheimer Foundation Scholar, and he received an Emerald Foundation Young Investigator Award. He is also a Department of Defense Era of Hope Scholar. Dr. Tavazoie is an attending medical oncologist at Memorial Sloan-Kettering Cancer Center.
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