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Stephen J. Weiss, MD
E. Gifford and Love Barnett Upjohn Professor of Internal Medicine & Oncology
Division of Genetic Medicine
Department of Internal Medicine
Rogel Cancer Center
Professor, Cell and Molecular Biology Program
Life Sciences Institute
University of Michigan
Ann Arbor, Michigan
Goal: To validate new therapeutic targets to prevent metastatic breast cancer (MBC).
Impact: Dr. Weiss has identified molecules that allow cancer cells to spread to distant sites in the body and grow as metastatic lesions. His work may identify new therapeutic targets to treat or prevent metastasis.
What’s next: He and his team will continue to investigate the roles played by the protein factors Snail1 , Twist1, and MTI-MMP in regulating breast cancer cell reprogramming, invasion, and metastasis.
The deadliest characteristic of breast cancer cells is their ability to spread to other tissues—a process called metastasis. Once this occurs, the disease is incurable. Dr. Weiss is conducting laboratory studies to understand the mechanisms underlying tumor progression, invasion, and metastasis, which could lead to the identification of specific factors that may be targeted as new therapeutic interventions in breast cancer patients.
Full Research Summary
Research goal: Characterizing the mechanisms underlying breast cancer cell metastasis in order to accelerate the design of new therapeutic interventions.
Impact: In breast cancer patients, morbidity and mortality arise as a result of cancer cells’ ability to invade local tissues, gain access to blood or lymphatic vessels, and exit at distant sites where the cells grow anew (a process called metastasis). Dr. Weiss is studying key proteins that appear to play dual roles in controlling the abnormal growth and invasive features of breast cancer cells, which may be important therapeutic targets in breast cancer growth and metastasis.
Current investigation: He and his team have identified and are focusing their work on a family of proteins that allow cancer cells to spread to distant sites in the body and grow as metastatic lesions. Included are 1) Snail1, a protein that controls breast cancer gene programs silencing the function of a normal tumor suppressor protein, p53, and 2) the related factor Twist1, which works with Snail1 to regulate the expression of MT1-MMP. MT1-MMP is an enzyme that acts like molecular “scissors” to cut through tissues, allowing cancer cells to metastasize.
What he’s learned so far: Using laboratory models, Dr. Weiss has shown that Snail1 promotes the ability of breast cancer cells to adopt life-threatening stem cell-like qualities and that Snail1 along with Twist1 triggers MT1-MMP to spread to distant sites and cause pathologic bone destruction.
What’s next: He and his colleagues will seek to understand the molecular mechanisms underlying breast cancer stem cell generation and the proteins that allow breast cancer cells to metastasize and damage distant tissues. The identification of these key drivers of breast cancer metastasis are central to Dr. Weiss’ goal of identifying new therapeutic targets.
After completing his postdoctoral training at Washington University, Dr. Weiss was recruited to the University of Michigan in 1982 where he assumed the rank of Professor in 1988. In 1991, he was named as the first recipient of the Upjohn Professorship in Oncology, a position that he continues to hold. Dr. Weiss has also served as the Director of the Molecular Mechanisms of Disease Program and the Chief of the Division of Molecular Medicine & Genetics in the Department of Internal Medicine at the University of Michigan as well as the Associate Director of Basic Science Research in the University of Michigan Comprehensive Cancer Center. In 2006, he joined the Life Sciences Institute as a Research Professor. He is a member of the American Society of Clinical Investigation, the Association of American Physicians, National Academy of Medicine, and served as the Editor-in-Chief of the Journal of Clinical Investigation.
Dr. Weiss’ research efforts have long focused on the mechanisms used by breast cancer cells to remodel tissue structures during tumor progression, invasion and metastasis. His studies on the roles of transcription factors and proteolytic enzymes (particularly Snail family members and the membrane-anchored matrix metalloproteinases, respectively) in regulating these pathologic events in vitro and in vivo have appeared in top-ranked journals such as Science, Nature and Cell.