BME Seminar Series Wednesday, April 9, 2014 9:30-10:20am MJIS 1001 Weldon School of Biomedical Engineering Purdue University Dynamical Feedback Circuits in Cell Biology: Integrative Network Analysis of Receptor/Ligand Signaling Pathways and Proteolytic Feedback Circuits Governing Invasive Cell Migration Douglas A. Lauffenburger<https://sharepoint.ecn.purdue.edu/coe/bme/gradseminar/_Layouts/listform.aspx?PageType=4&ListId=%7b408AAD34-A265-4638-925D-118DD8D80545%7d&ID=12>, Ph.D. Ford Professor and Head of Bioengineering Departments of Biological Engineering and Biology MIT Abstract: Biochemical signals induced by receptor tyrosine kinases (RTKs) governs mammalian cell behaviors involved in physiology and pathology. RTK signaling is, at the same time, regulated by processes influencing receptor/ligand binding; in recent years, activities of cell surface proteases such as ADAMs have become identified as a key locus for this regulation via shedding receptor and ligand ectodomains. These protease activities are, in turn, modulated by RTK signaling pathways. Thus, the traditional “upstream/downstream” perspective of receptor signaling to cell behavior is generally inadequate for understanding how pathological dysregulation transpires and may be treated by molecular interventions. In the context of malignant diseases including cancer and endometriosis, we have been pursuing a combined experimental/computational approach integrating multiple kinase signaling pathway activities, protease activities, and receptor/ligand shedding in order to determine regulatory network logic governing invasive cell migration. Applying our inferred network model to understanding effects of small molecule inhibitors for kinase pathways, we have identified an ADAM-based mechanism of drug resistance through reduced RTK shedding that can be overcome with appropriate inhibitor combinations. Most recently, we have probed clinical relevance of this mechanism to disease therapeutics with animal model and human patient studies. Bio: Prof. Doug Lauffenburger is the Ford Professor and Head of Biological Engineering, and Professor of Biology at MIT. His research program uses molecular and cellular bioengineering and quantitative biology techniques to study cellular signaling, receptor/ligand dynamics, cell migration, proliferation, differentiation and cell death applied to cancer and endometriosis. His lab has demonstrated that these approaches can be used to identify drug targets and molecular therapeutics to treat these diseases. Prof. Lauffenburger has co-authored more than 375 journal articles and book chapters, has won numerous honors and awards for his foundational work in systems biology and bioengineering, and is a member of both the National Academy of Engineering and the American Academy of Arts and Sciences. ~BME Faculty Hosts: Ann Rundell and Tamara Kinzer-Ursem~ *Sometime after 10:30AM on the day of seminar, go to the link http://boilercast.itap.purdue.edu:8080/ess/feed?id=847e407f-8a44-4b49-ba4b-f... to view a recording of that day’s seminar. Works well with Mozilla Firefox, will not work with Google Chrome. Thank you, Tamara Kinzer-Ursem Assistant Professor Weldon School of Biomedical Engineering Purdue University http://engineering.purdue.edu/ursemlab