Inflammation and Host Defense

Dr. Lisa M. Coussens

Dr. Coussens is Professor in the Pathology Department and Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco. The overall goal of her laboratory's research is to define the cellular and molecular determinants of the step-wise pathways mediating epithelial carcinogenesis. Her research is based upon the premise that, in addition to intrinsic changes occurring within neoplastic cells, e.g., activation of oncogenes and inactivation of tumor suppressor genes, extrinsic factors, e.g., extracellular matrix remodeling, immune response and angiogenesis, also control critical properties of tumor evolution. Her research team is currently investigating the role of innate and adaptive immune cells, complement activation, extracellular proteases (serine, cystein, metallo), and extracelluar matrix components, as regulators of cell proliferation, genomic instability, inflammation, angiogenesis, tumor stem cell activation and malignant potential. The long-term goal of this work is to translate basic observations made in the mouse, toward rational design of novel therapeutics whose aim will be to block and/or alter rate-limiting events critical for solid tumor growth or maintenance in humans. Dr. Coussens has received numerous awards including Hellman Family Award for Early Career Development, the Edward Mallinckrodt Jr. Foundation Award for Medical Research, the Gertrude B. Elion Cancer Research Award from the AACR, and the Era of Hope Scholar Award from the Department of Defense Breast Cancer Research Program.

Dr. Goran K. Hansson

Dr. Hansson is Professor of Cardiovascular Research at the Karolinska Institute and head of the Cardiovascular Research Laboratory in the Center for Molecular Medicine at Karolinska University Hospital in Stockholm, Sweden. Dr Hansson's research deals with immune and inflammatory mechanisms in atherosclerosis. In 1985, he discovered that the atherosclerotic plaque is the site of an inflammatory/immune response involving activated T cells and cytokines. His work has shown that low-density lipoprotein (LDL) elicits a cellular immune response, that immune cytokines activate vascular smooth muscle cells cells, and that the Th1 pathway is activated in atherosclerosis. His current work deals with proatherogenic and atheroprotective immunity, vascular inflammation, and myocardial infarction. Dr. Hansson has received numerous awards including the Anitschkow Prize from the European Atherosclerosis Society, the George Lyman Duff Memorial Award from the American Heart Association, and the Werk Prize from the Swedish Heart-Lung Foundation. Göran Hansson is a member of the Royal Swedish Academy of Sciences and of Academia Europaea.

Dr. Gokhan S. Hotamisligil

Dr. Gökhan S. Hotamisligil is the James Stevens Simmons Professor of Genetics and Metabolism and the Chair of the Department of Genetics and Complex Diseases at Harvard University's School of Public Health. Dr. Hotamisligil's research efforts focus on the genetic basis of common and complex diseases, particularly obesity, diabetes, and heart disease. His research examines the molecular mechanisms of nutrient sensing and response pathways as they relate to physiological metabolic homeostasis and also to these pathologies. His discoveries include the identification of molecular pathways that link obesity and diabetes, the identification of molecular links between pathogen and nutrient sensing systems, the discovery of JNK as a key inflammatory kinase involved in the integration of immune and metabolic responses and type 2 diabetes, and most recently, the identification of endoplasmic reticulum stress as a core mechanism that underlies systemic metabolic homeostasis. These studies have demonstrated that inflammation is at the heart of obesity, type 2 diabetes and other associated pathologies. Dr. Hotamisligil continues to be active in these areas and to pursue new interdisciplinary paths as he aims to develop novel preventive and therapeutic strategies.

Dr. Richard Locksley

Dr. Richard Locksley is the Sandler Distinguished Professor of Medicine and Microbiology & Immunology at UCSF, where he is the Director of the Sandler Asthma Basic Research Center. Dr. Locksley's laboratory focuses on the role of cytokines in organizing distinct types of immune responses against the various classes of pathogens. The major goal remains the understanding of how different types of innate and adaptive immune cells function to coordinate the response. Common strategies taken by the lab include the generation of cytokine reporter mice that allow the functional dissection of immunity as it unfolds in vivo. A major emphasis has been the understanding of allergic immunity, including how it is established and sustained in tissues, particularly in the lungs and the intestines. Current projects focus on the lineage tracking of eosinophils and basophils, the mechanisms by which Th2 cells organize allergic pathology, the regulation of mast cell responses in tissue by IgE and the understanding of how chitin recognition is mediated in driving allergic immune responses. Dr. Locksley is a fellow of the American Academy of Arts & Sciences and an Investigator in the Howard Hughes Medical Institute.

Dr. Gabriel Nunez

Dr. Gabriel Nuñez is the Paul de Kruif Professor of Pathology at the University of Michigan. For more than twenty years, Gabriel Nuñez has investigated molecular and cellular mechanisms involved in cell death, innate immunity and cancer. In early work, his laboratory made important contributions to the field of apoptosis, including the identification of multiple components of the cell death machinery and key regulatory steps in the apoptotic pathway. More recently, the Nuñez's laboratory identified Nod-like receptors (NLRs), a class of pattern-recognition molecules that mediate cytosolic sensing of microbial organisms. His laboratory showed that NOD2 mutations are associated with Crohn's disease, a common inflammatory disorder of the bowel. The involvement of NOD2 in the pathogenesis of Crohn's disease is considered an important discovery in the field of complex genetic diseases which has been confirmed by many laboratories around the world. In subsequent studies, the Nuñez and colleagues identified the molecular structures in bacteria that are recognized by several NLRs including NOD1, NOD2 and NLRC4 and characterized signaling pathways that are induced upon their activation. Nuñes the author of more than 200 peer-reviewed publications.

Dr. Fiona Powrie

Dr. Fiona Powrie is a Wellcome Trust Senior Fellow and Professor of Immunology at The Sir William Dunn School of Pathology, University of Oxford. Her early work identified CD4+ regulatory T cells that could suppress immune responses and whose absence led to inflammatory disease. In the last decade she has focused on immune regulation in the intestine. Her work has identified the functional role of regulatory T cells in intestinal homeostasis and shed light on their development and mechanism of action. She has also shown that both adaptive and innate immune mechanisms contribute to intestinal inflammation and identified the cytokine IL23 as a pivotal player in the pathogenesis of chronic intestinal inflammation. The research interests of Dr. Powrie's group include dissection of the factors that govern T cell responsiveness and non responsiveness in the intestine, identification of immune regulatory mechanisms (with particular emphasis on the role of T cell subsets and their cytokines) which lead to the development of tolerance to intestinal antigens and how a breakdown in these mechanisms may lead to the development of inflammatory bowel disease.

Dr. Herman Waldmann (The Severo Ochoa Lecture)

Dr. Herman Waldmann is Professor of Pathology and Head of the Sir William Dunn School at the University of Oxford. Dr. Waldmann's research is primarily concerned with exploring the mechanisms underlying immunoloigcal self-tolerance and harnessing this knowledge to reprogram the immune system for therapeutic benefit (i.e., to enable acceptance of transplants, reversal of auotimmune disease and allergies, and improvement of vaccines). In 1985 he published the first studies to show that short courses of CD4 antibody therapy could bring about long-term immunological tolerance to foreign proteins, and this work led on to the first demonstrations of transplantation tolerance resulting from short-tem antibody blockade. His interest in establishing the rules by which antibodies kill cells came from a desire to maximize lysis where desirable, and to blockade function without lysis as part of tolersnce protocols. The strategies emerging from the Waldmann laboratory since his seminal mechanistic studies of tolerance uncovered a role for regulatory T-cells in "infectious tolerance" in 1993 have been based on the use of therapeutic antibodies to enhance regulation over conventional T-cell immunity. In order to apply antibodies clinically Waldmann developed the first academic antibody therapeutic manufacturing facility. He and his team were able to apply clinical grade antibodies in a wide range of probing therapeutic studies which enabled them to develop a series of humanized antibodies (CD52, CD3, CD4 and others) which have since been transferred to the pharmceutical industry. His team's work since 1971 has resulted in more than 450 publications, the majority directed to therapeutic antibodies and their mechanisms of action. These contributions have led to his election to the Royal Society in 1990, and the award of the Jose Carreras medal of the European Hematology Society in 2005, the JDRF Excellence in Clinical Research Award in the same year, and the Starzl prize for Surgery and Immunology in 2008.