Chance vs. circumstance: a new paradigm for understanding local immune networks

Wednesdays@NICO Seminar, Noon, February 13, 2013, Chambers Hall, Lower Level

Prof. Josh Leonard, Northwestern University

Abstract

The Leonard Lab works at the interface of systems biology and synthetic biology in order to probe and program the function of complex, multicellular systems for applications in biotechnology and medicine. We are particularly interested in addressing the challenge of local immune dysfunction, which poses a persistent barrier to effective treatments for cancer as well as many other chronic diseases. In this talk, I will describe our experimental systems biology investigations into the mechanisms by which dysfunctional immune network states are established, maintained, and potentially may be disrupted therapeutically. This talk will focus on the contributions of macrophages, which are innate immune cells that play a critical role in maintaining the balance between homeostasis and protective inflammation by adopting either immunostimulatory or immunosuppressive phenotypes. Tumors and pathogens manipulate this balance by inducing the production of immunosuppressive stimuli, which shift macrophages into an phenotype that supports tumor survival and growth. Macrophages also exhibit functional “plasticity,” in that they can interconvert between states under certain circumstances. Despite the centrality of these phenomena to diverse disease processes, the mechanisms regulating macrophage “decision-making” remain relatively poorly understood. Here, we describe several novel systems-level insights into how such decisions are regulated, including the first evidence to date that macrophage functional polarization may be a stochastic process. I will also briefly describe our complementary computational investigations into these processes as well as several synthetic biology-based biotechnologies we are developing that will enable us to translate these insights into novel therapeutic strategies.

Biography

Joshua N. Leonard, Ph.D. is an Assistant Professor of Chemical and Biological Engineering in the McCormick School of Engineering and Applied Science and is a member of the Robert H. Lurie Comprehensive Cancer Center and Chemistry of Life Processes Institute at Northwestern University. Leonard received a B.S. in chemical engineering from Stanford University in 2000, and a Ph.D. in chemical engineering from the University of California, Berkeley in 2006, where he employed computational and experimental approaches to develop novel gene therapies for treating HIV infections. From 2006-2008, Leonard trained in immunology as a postdoctoral fellow at the Experimental Immunology Branch of the National Cancer Institute, where he elucidated a central aspect of the antiviral immune response and developed novel targeted vaccine adjuvants. In 2008, Leonard joined the faculty of Northwestern University. He also co-directs a graduate cluster in Biotechnology, Systems, and Synthetic Biology and mentors Northwestern’s international Genetically Engineered Machines (iGEM) team.

Leonard’s research group engineers novel biological systems that perform customized, sophisticated functions for applications in biotechnology and medicine. Using the tools of synthetic biology, biomolecular engineering, systems biology, and gene therapy, they develop technologies including programmable cell-based “devices” that make it possible to probe and modulate immune responses in a patient- and disease-specific fashion. They are applying this approach to develop new treatments for cancer, programmable smart vaccines, and inexpensive diagnostics for applications in global health. By bringing an engineering approach to the analysis, design, and construction of biological systems, the Leonard group is advancing the frontiers of design-based medicine to address unmet medical needs and create safe, effective, and long-lasting treatment options that improve both quantity and quality of life.