Stephen J. Weiss, M.D.

Stephen Weiss's research efforts have long focused on the mechanisms used by cancer cells, stem cells, the immune system and vascular network to proteolytically remodel tissue structure during events ranging from cancer and inflammatory disease states to embryonic development. His highly cited works on these subjects have appeared in top-ranked journals such as Science, Nature, Nature Cell Biology, Genes & Development, the Journal of Cell Biology, the Journal of Experimental Medicine, the Proceedings of the National Academy of Sciences, Developmental Cell and Cell.

Most recently, Weiss’ characterization of a family of membrane-anchored enzymes, the MT-MMPs, lends credence to his novel hypothesis that these proteolytic enzymes (generally termed, proteinases) act as master switches in controlling key functions of normal and neoplastic cell behavior in vivo.

When Weiss first embarked onto his current path of research, i.e., studying the functions and regulation of proteinases — he calls them "molecular scissors" — his lab had been working on reactive oxygen metabolites, small molecule oxidants that are generated by immune cells "that no one would have thought would be purposely generated in a biological system." One of the downstream products of these reactive species is hypochlorous acid (HOCl), the active ingredient in bleach, that is best known for its microbicidal effects. However, in a completely serendipitous fashion, the Weiss laboratory discovered that HOCl reacted with a specific proteinase, a type of molecular scissors named “collagenase” for its ability to cut/degrade type I collagen, a major structural protein found in all tissues. This unexpected intersection of a highly reactive oxidant with a proteinase resulted in the conversion of collagenase from an inactive, latent state to that of a fully active enzyme. As type I collagen is the dominant extracellular component found in mammalian tissues, this discovery sparked Weiss’ interest in understanding how cells remodel the extracellular tissues that serve as a structural scaffold for all cells in the body.

Cancer cells, stem cells and blood vessel cells also make molecular scissors — the human genome codes for more than five hundred varieties. Though these scissors are activated by other mechanisms that are operate independently of reactive oxidants, Weiss discovered new processes underlying their activation and is currently working on several interrelated projects exploring how normal and neoplastic cells mobilize these scissors "and use them to cut their way through surrounding tissues in order to grow, move, build new structures like blood vessels, and in the specific case of cancer, metastasize to distant organs.” A long-term goal of the lab is to identify those scissors that might be targeted in order to offer therapeutic benefit for diseases ranging from cancer to rheumatoid arthritis.

Having completed his B.A., M.D. and medical internship at Ohio State University and Washington University, Weiss was recruited to the Division of Hematology/Oncology at the University of Michigan in 1978 to complete his training. In 1982, he was promoted to the rank of Assistant Professor in the Department of Internal Medicine, Division of Hematology/Oncology and in 1988, assumed the rank of Professor. In 1991, he was named as the first recipient of the Upjohn Professorship, a title that he has held for the last 20 years. Weiss also served as the Division Chief of Molecular Medicine & Genetics in the Department of Internal Medicine and the Director of the Molecular Mechanisms of Disease Program before joining the Life Sciences Institute as a Research Professor in 2006. More recently, Weiss was appointed in 2016 as the Associate Director for Basic Science Research, a program encompassing more than 150 scientists, at the U-M Rogel Cancer Center.