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Stephen J. Weiss, MD
E. Gifford and Love Barnett Upjohn Professor of Internal Medicine and Oncology
Professor, Cell and Molecular Biology Program
Associate Director of Basic Science Research
University of Michigan
Ann Arbor, Michigan
- Seeking to validate new therapeutic targets to prevent metastatic breast cancer.
- Laboratory studies are conducted to characterize how tumor cells hijack normal processes to promote tumor cell invasion and metastasis.
- These studies may identify new therapeutic targets to treat or prevent metastasis.
The deadliest characteristic of breast cancer cells is their metastatic activity – meaning their ability to spread to other tissues. Metastatic breast cancer is the leading cause of breast cancer deaths and is an incurable disease. Dr. Weiss is conducting laboratory studies to understand how breast cancer cells learn to change tissue structures during tumor progression, invasion and metastasis. These studies will accelerate the design of therapeutic interventions targeting the newly identified molecules.
Full Research Summary
Normal breast cells (mammary epithelial cells) grow slowly and in a highly regulated fashion and are, by definition, confined to breast tissue. The exception to this is during periods of normal growth, such as embryonic development and puberty, when normal epithelial cells grow rapidly and move through different tissues. In contrast, breast cancer cells multiply uncontrollably, fail to maintain normal gland architecture, and acquire the ability to invade local tissues and metastasize.
Research suggests that cancer cells inappropriately reactivate genetic programs that are normally used only during development. Dr. Weiss's laboratory has identified two key molecules that appear to play dual roles in controlling the abnormal growth and invasive features of breast cancer cells. These molecules, called Snail1 and MT1-MMP, may be important therapeutic targets in breast cancer growth and metastasis.
Snail1 is not expressed in normal adult mammary epithelial cells, but as cancer develops and progresses, Snail1 protein levels begin to increase inappropriately. Snail1 works closely with a second protein, Snail2 (a.k.a Slug), in regulating the expression of MT1-MMP, which acts like a type of molecular scissors that allows cancer cells to “cut” their way through tissues to metastasize.
The key roles played by the Snail proteins and MT1-MMP in driving breast cancer growth and metastasis support the development of new agents designed to inhibit their expression and activity.
In the coming year, Dr. Weiss and his team will expand these studies to define the role of these two factors in breast cancer progression and test strategies to target MT1-MMP or Snail1/Snail2 to prevent metastasis.
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. 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, Institute of Medicine of the National Academy of Sciences, and has 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, Genes & Development, the Journal of Cell Biology, the Proceedings of the National Academy of Sciences and Cell.