Metastasis as a Heritable Disease Shaped by Our Infectious Evolutionary History and Nervous System
Event Details
- Type
- Monday Lecture Series
- Speaker(s)
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Sohail Tavazoie, M.D., Ph.D., Leon Hess Professor, senior attending physician and head, Elizabeth and Vincent Meyer Laboratory of Systems Cancer Biology, The Rockefeller University
- Speaker bio(s)
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Metastasis causes most cancer deaths, yet its genetic and physiological origins remain unresolved. Our lab studies the molecular mechanisms underlying this fascinating biological process, where rare cancer cells achieve extreme gene expression states that enable travel to distal organs and formation of lethal metastatic colonies that evade multiple physiological barriers. The prevailing view has held that rare “metastasis-driver” somatic mutations arise within tumors and enable this process. Decades of sequencing have not revealed such causal drivers. I will present evidence for an alternative model in which germline genetic variation can establish metastatic potential before tumor formation. Our work has shown that common human APOE genetic variants differentially promote or suppress melanoma metastasis by altering immune, vascular, and tumor biology. Our findings reveal clinically relevant trade-offs for APOE across melanoma progression, Alzheimer’s disease risk, and infectious disease. I will provide further support for this germline model by describing our recent identification of a second germline regulator of metastasis in breast cancer. I will finally describe a complementary story describing a causal role for DRG sensory neurons and the substance P neuropeptide in breast cancer metastasis. Together, these studies reframe metastasis as an outcome resulting from inherited gene variants and neural signals interacting with tumor programs, with implications for risk stratification, prevention, and therapeutic targeting of neural and inherited genes.
Dr. Sohail Tavazoie is the Leon Hess Professor and Head of the Meyer Laboratory of Systems Cancer Biology at The Rockefeller University. He received his undergraduate degree from the University of California at Berkeley and his M.D. and Ph.D. degrees from Harvard Medical School. Following internship and residency training at Brigham and Women’s Hospital and postdoctoral training at Harvard, he conducted oncology fellowship training at Memorial Sloan Kettering Cancer Center. Sohail has been the recipient of the NCI Outstanding Investigator Award and the DOD Era of Hope Award. He is an elected member of the National Academy of Medicine and the past president of the American Society of Clinical Investigation. Sohail's lab studies the molecular and genetic mechanisms underlying cancer metastasis and they apply these insights towards the development of novel experimental therapeutics that target the biology of metastatic disease.
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- Open to
- Campus Only