Denis Wirtz, Theophilus Halley Smoot Professor in the Department of Chemical and Biomolecular Engineering and vice provost for research at Johns Hopkins University, is known for his studies of the molecular and biophysical mechanisms of cell motility and adhesion and nuclear dynamics in health and disease, with a special focus on aging, cancer, and progeria. Wirtz directs the Johns Hopkins Physical Sciences-Oncology Center and co-directs the Cancer Nanotechnology Training Center, both National Cancer Institute-funded entities. He is a co-founder and former associate director of the Johns Hopkins Institute for NanoBioTechnology.
Wirtz studies the biophysical properties of healthy and diseased cells, including interactions between adjacent cells and the role of cellular architecture on nuclear shape and gene expression. Cell biophysics, single-molecule manipulation, intracellular particle trafficking, instrument development, tissue engineering, and nanotechnology in biology and medicine are among his research interests.
Wirtz’s advances were made possible by his pioneering role in developing the method of particle-tracking microrheology to probe the rheological properties of complex fluids and living cells and tissues. His design of particle tracking microrheology in complex fluids is now a standard technique used in cell mechanics studies and many chemical industries. The technique measures several properties of materials at the femtoliter scale (1015) and allows researchers to probe thousands of materials in a short period of time while remaining cost-effective. Researchers can now characterize materials and find better ways to use them.
His work in studying cells in a natural, three-dimensional environment (versus a two-dimensional environment) changed how researchers view and investigate cell migration and adhesion—two main drivers of disease—inflammation, and tumorigenesis. While researchers had been using three-dimensional environments for other reasons, they didn’t make the connection in how it affects the way cells migrate. Wirtz did.
Another contribution is in the area of cell and nuclear mechanics, where Wirtz’s group developed novel tools and concepts to study the role of nucleus and nuclear connections to the cytoskeleton and key cell functions, including 2D and 3D cell migration and adhesion, mechanosensation, and mechanotransduction. In particular, the group identified LINC complexes and the so-called perinuclear actin cap as key mediators of physical signaling between the cytoplasm and the nuclear interior. More recently, they discovered that the nuclear lamina of adherent cells is polarized through the actin cap, which in turn polarizes hyper-acetylated forms of histones in the nucleus.
Wirtz also developed a new test, high-throughput cell phenotyping (htCP), to measure hundreds of cell morphological parameters in tissues and culture in seconds. Since the test reveals the cells’ heterogeneity, or how a cell processes and responds to internal and external mechanisms, it can predict how the cell will respond to disease and age, and can also be used to test and predict drug responsiveness and outcomes. Mostly used in academia, many biological research companies in the commercial sector, as well as laboratories, are now using this test.
Wirtz also discovered that when cancer cells proliferate, they produce two molecules, interleukin 6 and interleukin 8. These molecules are known to be produced by immune cells in the context of inflammation, but they were not known to be produced simultaneously or by cancer cells. With this knowledge, early stages of a clinical trial are underway to test a combination of two drugs for arthritis to treat pancreatic and triple-negative breast cancer as a potential therapy to prevent metastasis and to become a standard cancer care treatment.
Wirtz was elected Fellow of the American Association for the Advancement of Science (2009) for his contributions to cell micromechanics and cell adhesion. AAAS also recognized Wirtz for his development and applications for particle tracking methods to probe the micromechanical properties of living cells in normal conditions and disease state. He is a fellow of the American Physical Society (2010) and the American Institute for Medical and Biological Engineering (2007), and a past recipient of the National Science Foundation’s CAREER Award and the Whitaker Foundation Biomedical Engineering Foundation Award.
Wirtz earned a bachelor’s degree from the Université Libre de Bruxelles in Belgium (1988) and master’s and doctoral degrees in chemical engineering from Stanford University (1993). He did postdoctoral research at the Ecole Supérieure de Physique et Chimie Industrielles (ESPCI) in Paris, France.