Immunology

The Immunology Ph.D. program is an interdepartmental program offering training in immunology and related basic and clinical biomedical sciences. The program involves approximately 46 faculty members in 13 different departments in the Medical School and in the Department of Biological Sciences, in the School of Humanities and Sciences.
       The research interests of our faculty cover the major areas of modern immunology including cellular immunology, molecular immunology, clinical immunology, structural immunology, and many aspects of the function of the immune system in each of these areas. Research includes studies of the development and function of T- and B-lymphocytes, natural killer cells, regulatory T-cells, and the specific tissues and organs that contribute to host defenses. The program has a strong molecular component and many of the laboratories have focused on key molecules in the induction and expression of immune responsiveness. These include the molecules encoded by the major histocompatability complex, T-cell receptors, immunoglobulins, costimulatory and accessory molecules, adhesion molecules, including selectins and integrins, and chemoattractant receptors. Studies in progress range from analysis of gene expression using microarrays and robotic sequencers, to studies of and the 3-dimensional structure of a number of important proteins by protein crystallography. A number of faculty are focusing on the cellular interactions that are characteristic of lymphocytes, from the architecture of the “immunological synapses” that they form to the specific molecular interactions and signaling cascades that accompany activation, beginning with their characteristic cell surface receptors, intracellular signal transduction molecules, and transcription factors regulating gene expression in immune cells. Another major strength of the program is the wealth of new tools and technologies available to immunologists that are well supported here by key laboratories and core facilities in the Immunology Program. These include confocal microscopy for cell imaging, cDNA microarrays of both mouse and human genes for gene expression profiling, large scale microarrays for antibodies to proteins, lipids and carbohydrates, and transgenic core facilities, as well as the availability of a large reservoir of transgenic and knock-out mice strains for use in all of these studies.
       In addition to Stanford’s strength in basic immunology, the Immunology IDP faculty are also pushing the boundaries of traditional immunology by demonstrating pervasive and significant roles for immune-derived cells and factors in the regulation of numerous and varied non-immunologic processes. These novel findings have created new paradigms in diverse and previously unrelated fields ranging from metabolism to neuroscience to aging and opened new arenas to investigation. A number of faculty focus on the applications of these basic findings to clinical diseases, ranging from type I diabetes mellitus, multiple sclerosis, and rheumatoid arthritis to a number of infectious diseases, allergy and several types of cancer. In many of these diseases, mechanisms of self-tolerance fail and the immune system begins to react against itself in autoimmunity, or fails to react adequately against new proteins expressed in cancer cells. Array methodologies for autoantibody detection in autoimmune patients and for functional T-cell profiling in vaccine studies have also been pioneered at Stanford.
       To maintain optimal communication, cooperation and interaction, the program sponsors weekly seminars, journal clubs in several disciplines, and an annual 3-day retreat to facilitate as much interaction as possible between students, post-doctoral fellows and faculty in the immunology community at Stanford.

For more information contact:
Maureen Panganiban
Program Administrator
300 Pasteur Drive
Alway Building, Suite M-105, Room M103c
Stanford, CA 94305-5121
(650) 725-5076
(650) 725-3867 (fax)
mopan@stanford.edu
http://immunol.stanford.edu

Faculty and their Research Interests

Ann Arvin. Varicella-zoster virus (VZV): molecular mechanisms of replication and pathogenesis-identification of functional domains of viral genes/promoters, roles of viral and host cell proteins in pathogenesis of VZV infection of T-cells, skin, neurons in SCIDhu model; CD4/CD8 T cell immunity to VZV; viral mechansisms of immune evasion.

Eugene Butcher. Molecular and cellular biology of lymphocyte and neutrophil homing; cell adhesion and chemotaxis in immune responses; reproductive immunology; systems biology of the immune system.

Ajay Chawla. Activation of macrophage and dendritic cells by nuclear receptors: crosstalk between cellular metabolism and inflammation. Role of peroxisome proliferator activated receptors (PPARs) in macrophage activation, deactivation and antigen presentation.

Yueh-hsiu Chien. Molecular nature of gamma-delta T-cell recognition and function. Molecular mechanisms of bacterial infection and host immune responses. Contribution factors to immunocompetence and autoimmunity.

Gilbert Chu. Recognition and response to DNA damage; role of proteins in biochemical pathways for DNA repair.

Michael Cleary. Molecular and cellular biology of hematologic malignancies; role of leukemia oncogenes in mammalian development.

Christopher H. Contag. Revealing immune cell trafficking patterns in vivo through whole body imaging to understand immune function, cell-cell and cell-tissue relationships through development and in response to insult.

Gerald R. Crabtree. Genetic regulatory mechanisms in T-lymphocyte activation; lymphoid development.

Mark M. Davis. Molecular mechanisms of lymphocyte recognition and differentiation; molecular genetics and expression of T-cell receptor genes.

Anthony De Tomaso. Using a combination of genetic, genomic, and cell-biological approaches, we are studying the phenomenon of self/non-self recognition in a primitive chordate organism, Botryllus schlosseri. This interaction links together a number of disparate fields, including immunology, stem-cell, developmental, and evolutionary biology, and also, has ecological consequences. Several unique aspects of the Botryllus life history make it a novel, experimentally accessible model organism to ask pertinent questions in these distinct disciplines.

Firdaus Dhabhar. I am interested in identifying biological mechanisms that mediate and differentiate the recently appreciated immunoenhancing effects of short-term stress from the long-known immunosuppressive effects of chronic stress. We examine stress effects on leukocyte trafficking, innate/adaptive immunity, and cytokine gene/protein expression using models of skin immunity, surgery, and cancer.

Edgar Engleman. Human dendritic cells and T-cells; genes that regulate the functions of these cells; ontogeny of dendritic cells; immunotherapeutic approaches to cancer, AIDS, and autoimmune diseases.

C. Garrison Fathman. Mechanisms of disease pathogenesis and autoimmunity; preclinical models of immunotherapy in animal models; T-cell signalling.

Dean Felsher. Role of oncogenes in the initiation and maintenance of hematopoietic tumorigenesis, including analysis of the effects of oncogenes on lymphocyte proliferation and differentiation.

Magali Fontaine. At the frontier of transfusion medicine and transplantation immunology, cellular therapy. Optimization of cell isolations such as islets of Langerhans for patients with type 1 diabetes. Invitro assays to monitor islet cell viablity, function, and tolerogenicity.

Stephen J. Galli. Regulation of mast cell and basophil development, heterogeneity and function, and roles as effector or immunoregulatory cells in health, host defense (in acquired and innate immunity) and disease; asthma and inflammation, especially allergic inflammation.

K. Christopher Garcia. Molecular immunology. Biochemical and structural studies of cell-surface receptor/ligand interactions with relevance to human health and disease. Applying biophysical and protein engineering approches to molecular problems in T-cell recognition, B-cell differentiation, innate immunity, and emerging molecules at the interface of immune and nervous systems.

Leonard A. Herzenberg. Gene regulation; lymphocyte subsets; molecular immunology; fluorescence-activated cell sorter development (FACS); AIDS; apoptosis; redox regulation.

Leonore A. Herzenberg. B-cell development; Ig rearrangement and repertoire analysis; signaling processes; impact of glutathione deficiency in HIV and other diseases; High-Definition Fluorescence-Activated Cell Sorting (Hi-D FACS); knowledge-based software to support FACS and other biomedical experimentation.

Patricia P. Jones. Genetic, cellular, and molecular mechanisms that regulate adaptive immune responses (the antigen-specific responses carried out by B and T lymphocyte, unique to vertebrates), and innate immune responses (responses present in both invertebrates and vertebrates triggered by microbial components).

Sheri Krams. Apoptosis in transplantation; activation of NK cells; mechanisms of tissue damage in liver disease.

Calvin Kuo. Characterization of novel chemokine receptors through knockout strategies in mouse and zebrafish; study of inflammatory effects on angiogenesis; and effects of Wnt, Hh and Notch pathways on the immune response.

Peter P. Lee. Biology of the T-cell responses to cancer in human patients; immunological characteristics of tumor-specific T-cells (endogenous and post-treatment) using peptide/MHC tetramers, multi-color FACS analysis, functional assays and cloning, and cDNA microarrays; also integration of these data into a non-linear dynamical system using mathematical modeling and simulations with the Bio-X supercomputer.

Ronald Levy. Immunology and molecular biology of lymphoid malignancy; molecular vaccines.

Shoshana Levy. Study of tetraspanins; the immunoregulatory role of the CD81 (TAPA-1), characterization of the new tretraspanins. Vaccine development; polarizing immune responses by antigen-cytokinefusion proteins and DNA constructs.

David B. Lewis. Cellular and molecular mechanisms limiting T-cell effector function during postnatal life; Th2 cytokine-mediated diseases involving the lung.

Richard S. Lewis. Biophysical mechanisms and cellular functions of calcium signaling during T cell activation and development. Imaging T-cell development in vivo with two-photon microscopy, and the role of calcium dynamics in controlling the specificity of gene expression.

Joseph Lipsick. Function and evolution of the Myb proteins: regulators of the cell cycle, chromosome structure, and gene expression.

Olivia Martinez. Cytokine regulation of alloreactivity; immunology of EBV B cell lymphomas; cellular and molecular mechanisms of graft selection and tolerance induction.

Hugh McDevitt. Structure and function of mouse and human class II MHC molecules, and their role in autoimmunity, focusing on type 1 diabetes in the non-obese diabetic mouse model.

Elizabeth Mellins. Antigen processing/presentation; structure/function of MHC class II molecules, including HLA-antibodiesDM; mechanisms of pathogen evasion of the class II pathway, with a focus on B. pertussis and human CMV; development of antigen presentation function in the human infant.

Sara Michie. Lymphocyte/endothelial adhesion and activation mechanisms involved in lymphohocyte migration into lymphoid tissues and sites of inflammation.

David Miklos. Investigates the targets of immune responses after human allogeneic stem cell transplantation. BMT patients develop antibodies against minor histocompatibility antigens (mHA) that are associated with chronic graft-v-host disease (cGVHD) and disease remission. Current projects: investigate Ab anti-tumor mechanism, high-throughput serologic identification of novel mHA in the development of GVHD and prevention of disease relapse, and clinical trials of B cell therapeutics for cGVHD.

Robert Negrin. NK-T cells, gamma-delta T-cells, in vivo imaging and tumor models, hematopoietic cell transplantation.

Garry Nolan. NF-kB and Rel signaling in B- and T-cells; HIV-1, retrovirology and retroviral libraries for gene transfer and mammalian complementation cloning.

Peter Parham. Role of MHC Class I molecules in presenting antigens to cytotoxic T lymphocytes and regulating natural killer cell; evolution of the immune system.

William Robinson. Mechanisms of autoimmunity; use of preclinical models to develop immunotherapeutic approaches to autoimmunity; proteomics and lipidomics; autoantibodies and B cells; translational research.

David Schneider. Using the fruit fly Drosophila as a model vector to study the cell biology and genetics of malaria transmission.

Judith Shizuru. Transplantation of defined populations of allogeneic hematopoeitic cells. How hematopoeitic cell grafts alter antigen specific immune responses to allo-, auto-, and viral antigens. The cellular and molecular basis of resistance to engraftment of allogeneic hematopoietic stem cells.

Raymond Sobel. Cellular and molecular mechanisms of immune reactions in the central nervous system, particularly in multipole sclerosis, EAE and other animal models.

Lawrence Steinman. Autoimmune diseases of the nervous system; inflammatory response in neuro-degenerative disease; multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and polyglutamine repeat diseases.

Samuel Strober. Induction of immune tolerance in bone marrows and organ transplantation, T-cell progenitor development in the bone marrow. Pathogenesis and treatment of systemic lupus in mice and man, regulatory NK T-cells and CD1.

Man-Wah Tan. Genetics and genomics dissection of host-pathogen interactions using a multipathogen C. elegans pathogenesis system; genetics and molecular analyses of signaling pathways in host innate immune response.

Paul J. Utz. Role of stress and apoptosis signaling pathways in autoimmunity; post-translational modifications of autoantigens; auto-antibodies and autoantigens; auto-antigen microarrays and micro-fluidics; proteomics assay development; tolerizing DNA therapy for SLE and related autoimmune diseases.

Irving L. Weissman. Developmental biology of the immune system, including analysis of hematopoeitic stem cells, T-cell differentiation, lymphocyte homing receptors, and killer T-cell genes.

Tony Wyss-Coray. We focus on the use of genetic and molecular tools to dissect injury and inflammatory pathways in Alzheimer’s disease and neurodegeneration.