Cancer Immunology and AIDS
Harvey Cantor, MD, Chair
The Department of Cancer Immunology and AIDS investigates fundamental questions in the development and expression of immune responses in cancer and autoimmune disease and the closely related problem of acquired immunodeficiency syndrome (AIDS) induced by the human immunodeficiency virus (HIV). A shared assumption of these two research efforts is that insight into the molecular and cellular events that regulate the immune response will have an important impact on clinical approaches to cancer and AIDS. Major research goals of the department include understanding the requirements for effective innate and adaptive host immune responses and developing adoptive cellular therapies and vaccines against cancer and AIDS.
The department's mission also includes teaching and training graduate and postdoctoral students. Faculty are actively involved in graduate education through programs in immunology, virology, and biological and biomedical sciences at Harvard Medical School (HMS). Two training grants, funded by the National Institutes of Health and directed by Harvey Cantor, MD, support postgraduate training in cancer immunology and AIDS research. In addition, members of the department actively participate in the Cancer Immunology Program of the Dana-Farber/Harvard Cancer Center, whose mission is to accelerate translation of fundamental advances in immunology to the clinic and improve the lives of patients with cancer. Faculty use new insights into the basic mechanisms that regulate the immune response to facilitate more effective approaches in the clinical areas of bone marrow transplantation, adoptive therapy, and vaccines.
In recent years, recruitment of both senior and junior HMS faculty has enriched the department. Harald von Boehmer, MD, PhD, is a professor of pathology; Koichi Akashi, MD, PhD, is an associate professor of pathology; and Shannon Turley, PhD, Koichi Kobayashi, MD, PhD, and Carl Novina, MD, PhD, are assistant professors of pathology.
Cancer Immunology
Lymphocytes that develop in the thymus (T lymphocytes) are critical immunologic cells that detect and orchestrate the response to both tumor and viral antigens. Generating antitumor or antiviral immunity depends on the maturation of T cells in the thymus and the successful activation of T cells by tumor or viral antigens in peripheral tissues. Research into the molecular mechanisms that regulate these responses is a key focus of the department in an effort to develop strategies that will augment or suppress the immune response.
T cell development
Dr. Akashi's studies of the molecular mechanisms responsible for differentiation and self-renewal of stem cells are helping to develop potential approaches to overcome immunodeficiency and augment anticancer immune responses. Dr. von Boehmer has identified unique signaling capabilities of the pre-T cell receptor that may play a role in leukemia, and mechanisms in thymic generation of regulatory T cells that have important implications in immunosuppression.
T cell activation
Kai Wucherpfennig, MD, PhD, has dissected the molecular structure of the T cell receptor and other activating receptors, thereby elucidating their distinct functions in the immune system. Martin Hemler, PhD, studies the family of cell surface molecules known as integrins and has shown their importance in lymphocyte and tumor cell metastasis. Edmond Yunis, MD, continues to study the role of genetic polymorphisms of human leukocyte antigen (HLA) molecules in human disease.
Development and function of immunologic cells
Dr. Turley investigates the development, differentiation, and function of dendritic cells in the primary immune response. Dr. Kobayashi studies mechanisms of the innate and adaptive immune system, while Dr. Novina focuses on the mechanisms and applications of mammalian RNA interference and microRNAs in lymphocyte-specific gene regulation. Dr. Cantor identifies and characterizes genes that regulate the immune response including osteopontin, which enhances type 1 (cell-mediated) immunity, and genes, such as MINK, that regulate the signaling pathways involved in the deletion of self-reactive cells. The laboratory of the late Stanley Korsmeyer, MD, has continued the molecular dissection of the intracellular events that lead to programmed cell death, or apoptosis, in lymphoid cells and other cell types. Stuart Schlossman, MD, examines the functional programs of T lymphocytes in the human immune system, while Jack Strominger, MD, studies human immature dendritic cells and microglia of the central nervous system.
AIDS
Research into the immunology, virology, and cell biology of HIV infection has expanded with the integration of the Dana-Farber and HMS Centers for AIDS Research and with faculty participation in several vaccine-based initiatives at DFCI and HMS.
Pathogenesis
The research of Joseph Sodroski, MD, has furthered our understanding of HIV pathogenesis through identification of the HIV-1 gp120 glycoprotein and its critical role in binding and fusing virus to host, as well as killing T lymphocytes. Dana Gabuzda, MD, focuses on the molecular mechanisms of HIV replication and pathogenesis, particularly in the central nervous system. Alan Engelman, PhD, studies viral integration of HIV into DNA, which has led to the characterization of novel cellular resistance factors that regulate this critical step in the viral life cycle. And Heinrich Göttlinger, MD, continues to dissect the interactions between HIV gag proteins and the relationship of gag to cytopathogenicity and viral tropism.
Therapy
The research of Ruth Ruprecht, MD, PhD, is aimed at developing vaccines based on passive immunization using monoclonal antibodies as well as on active vaccine strategies against both HIV and breast cancer. Dr. Sodroski is using insights into the structure of gp120 to develop active vaccination strategies. Dr. Gabuzda has identified the viral infectivity factor as a potential target for antiviral therapy, while Wayne Marasco, MD, PhD, continues to develop and test novel immunotherapeutics based on intracellular expression of antibodies directed against components of HIV, cancer, and infectious diseases.
