CBE Seminars & Events
Britton Chance Distinguished Lecture in Engineering and Medicine
The 2013 Britton Chance Distinguished Lecture in Engineering and Medicine sponsored by the Department of Chemical and Biomolecular Engineering.
Melody A. Swartz
Professor, Lymphatics and Cancer Bioengineering
Ecole Polytechnique Federale De Lausanne
"Lymphatic Vessels: Where Biotransport Meets Immunity"
Wednesday, December 4, 2013, 3:00 PM, Wu and Chen Auditorium, Levine Hall
While the traditional view of lymphatic vessel function is to drain excess fluid from peripheral tissues and return them to the blood circulation, there is a growing appreciation for lymphatic endothelial cells (LECs) as important players in immunity, as they are the first cells that come into direct contact with peripheral antigens, cytokines, danger signals and immune cells travelling from peripheral tissues to lymph nodes. They also form conduits in the lymph node that direct different molecules to different cells, for example to B cells and immature dendritic cells, in turn helping to regulate the spatial and temporal kinetics of antigen presentation.
Our lab aims to understand how lymphatic transport functions affect and regulate immunity, which has led to new discoveries of LEC immune functions. For example, we recently demonstrated that LECs can take up exogenous antigens and load them intracellularly onto MHC class I molecules (a process referred to as cross-presentation), and directly present them to naïve T cells, leading to immune tolerance. The extent to which LECs scavenge vs. transport antigens depends on danger signals and cytokines present locally, which they also sense. Furthermore, in contrast to passive drainage, which is driven by translymphatic pressure differences, we are now appreciating the degree to which LECs can actively transport fluid and molecules by nonspecific vesicles. By directly controlling local lymphatic drainage rates, LECs not only regulate the kinetics of antigen transport to the lymph node but also modulate local interstitial flow. This interstitial flow can, in turn, help direct dendritic cells to the lymphatic vessel by virtue of a phenomenon we have termed autologous chemotaxis, whereby DCs express both lymphoid chemokines and their receptor and upon secretion, local gradients form by interstitial flow, chemotactically directing the DC to the lymphatic vessel. Thus, lymphatic vessels help shape immune responses through both physical and molecular mechanisms that are inherently coupled. We believe that integrative studies of lymphatic transport physiology with immunobiology is critical in revealing and understanding the key roles that lymphatic vessels play in cancer progression and metastasis as well as chronic inflammation and autoimmunity.
Melody A. Swartz is Professor in the Institute of Bioengineering and the Swiss Institute for Experimental Cancer Research in the Faculty of Life Sciences as well as the Institute of Chemical Sciences and Technology, of the Ecole Polytechnique Fédérale de Lausanne (EPFL). Previous to moving to Lausanne, she was an Assistant Professor in Biomedical Engineering and Chemical Engineering at Northwestern University. She holds a BS from the Johns Hopkins University, and a PhD from Massachusetts Institute of Technology. She undertook postdoctoral studies at Harvard Medical School in Boston. Trained as a bioengineer, she uses quantitative approaches in cell biology and physiology, including biotransport and biomechanics, to investigate the role of the lymphatic system in physiology and pathophysiology. She is particularly interested in the role of the lymphatic drainage in maintaining immunological tolerance in homeostasis, and the role of lymphangiogenesis in controlling inflammation as well as inducing pathological tolerance in cancer. Her lab applies this knowledge to develop novel immunotherapeutic approaches in cancer, including lymph node-targeting vaccine approaches.
Previous Britton Chance Distinguished Lecturers
|1995||-||Lewis S. Edelheit, General Electric Company|
|1996||-||Douglas A. Lauffenburger, Massachusetts Institute of Technology|
||George Georgiou, University of Texas at Austin|
|1999||-||Jeffrey A. Hubbell, University of Zürich|
|2000||-||W. Mark Saltzman, Cornell University|
|2001||-||Chaitan S. Khosla, Stanford University|
|2002||-||Sangtae Kim, Lilly Research Laboratories|
|2003||-||Larry V. McIntire, Rice University|
|2004||-||Deborah E. Leckband, University of Illinois at Urbana-Champaign|
|2004||-||Stephen R. Quake, Stanford University|
|2005||-||Frances H. Arnold, California Institute of Technology|
|2006||-||Adam P. Arkin, University of California at Berkeley|
|2007||-||Kristi S. Anseth, University of Colorado at Boulder|
|2008||-||Jay D. Keasling, University of California at Berkeley|
Mark E. Davis, California Institute of Technology
David A. Tirrell, California Institute of Technology
Frank S. Bates, University of Minnesota
Arup K. Chakraborty, Massachusetts Institute of Technology