Robert Goldstein, M.D., Director, DAIT
Dr. Goldstein announced that Dr. Janet Connolly has joined the staff of the Division of Allergy, Immunology and Transplantation (DAIT) as the Chief of the Genetics Section in the Genetics and Transplantation Branch. Dr. Connolly is a nationally known researcher whose area of expertise is T cell immunobiology, including both cellular and molecular studies of alloreactivity.
Dr. Goldstein announced also that under the auspices of the NIH Transplantation Research Coordinating Committee, chaired by the NIAID, a meeting was held on August 15, 1996 titled Enhancing Organ donation: State of the Art and Future Directions. The meeting included representatives from eight Organ Procurement Organizations (OPOs) throughout the country. The American Society of Transplant Physicians, the United Network of Organ Sharing, the U.S. General Accounting Office, the Health Care Financing Administration, and the Juvenile Diabetes Foundation International were also present at this meeting. The focus of the meeting was factors affecting performance and remaining obstacles to improving organ donation.
Invited Council members and guests presented their current research efforts in the area of mucosal immunity: Moderator, Dr. Elaine Collier, National Institute of Allergy and Infectious Diseases (NIAID), Chief, Autoimmunity Section, DAIT reviewed Mucosal Immunity Research at NIAID; Dr. Michael Brenner, Brigham and Women's Hospital: Mucosal Lymphocyte Homing and Adhesion; Dr. Charles Wira, Dartmouth Medical Center: Hormonal Regulation of Mucosal Immunity in the Human Female Reproductive Tract; Dr. Charles O. Elson, University of Alabama at Birmingham: Strategic Defense at Mucosal Surfaces: Mucosal Vaccines; Dr. Warren Strober, Laboratory of Clinical Investigation, NIAID: Immunologic Mechanisms Underlying Mucosal Inflammation.
Fifteen concepts were presented, discussed and approved.
Autoimmunity: Genetics, Mechanisms, and Signaling:
The goal of this concept is to support new and innovative investigator- initiated basic and preclinical research into the immune response underlying autoimmune disease and its regulation for preventive or therapeutic purposes. Three specific areas of emphasis are highlighted 1) genetic susceptibility for autoimmune disease, including the MHC and other genetic sites; 2) the role and regulation of co-stimulation in autoimmunity; and 3) signal transduction in the autoreactive response.
Prevention of Insulin-Dependent Diabetes Mellitus:
This concept is to extend co-funding of the Diabetes Prevention Trial - Type 1 until the projected end of the trial. The Diabetes Prevention Trial - Type 1 (DPT-1) is a large multi-center clinical trial to investigate whether the use of low dose subcutaneous insulin or oral insulin will prevent or delay the development of diabetes mellitus in first degree relatives of patients with Insulin Dependent Diabetes Mellitus (IDDM). As of May 31, 1996 the trial had screened greater than 37,500 relatives of patients with IDDM. Safety studies for specific arms of the trial are complete and participants will be randomized beginning in early September, 1996.
Inflammation in Asthma and Allergy:
This concept will support studies of the underlying mechanisms of inflammation in asthma and allergic diseases. The goal of expanded efforts in this area is to promote innovative research to identify factors responsible for initiation and maintenance of inflammation in asthma and allergic diseases. Emphasis will be placed on innovative research in currently under funded areas of opportunity.
Innate Immunity:
This concept is to support innovative research on mechanisms of innate immunity and to promote new clinical applications of the knowledge gained. Innate immunity is phylogenetically older, and is often viewed as a vestige of ancient antimicrobial systems made redundant by the evolution of acquired immunity. This notion is now being challenged by the discovery of many robust mechanisms of innate immunity and by the recognition of important functional links between innate and acquired immunity.
Genes and Mechanisms Underlying Primary Immunodeficiency:
This concept will support innovative investigator-initiated research focused on the genes and mechanisms that lead to primary immunodeficiency diseases. The objective is to understand the molecular basis of primary immunodeficiency diseases in order to develop more effective diagnostics and treatment. In addition it is expected that the information generated about normal immune system function will lead to new approaches for other immune system mediated diseases.
Generation and Maintenance of Immunological Memory:
This concept would support multi disciplinary studies to elucidate basic mechanisms involved in determining whether the outcome of antigen encounter by T or B lymphocytes is long-term memory or cell death. The objective is to elucidate the basic mechanisms responsible for the generation, maintenance and functional diversity of memory B and T lymphocytes, in order to provide much needed information for improved vaccine development for infectious disease and novel therapeutic approaches to the treatment of autoimmune disease, transplant rejection and cancer growth.
Immune Response in Xenotransplantation:
This research concept is aimed at determining the type and extent of the immune response to antigens found on the surface of non-human organs or tissues or cells that might be used for transplantation into humans. Support would also be provided to develop new methodologies for specific and rapid diagnostic tests to identify possible pathogenic organisms that might be introduced into humans as a result of the implantation of organs, tissues or cells from non-human species. The research would be multi disciplinary, involving transplant immunologists, infectious disease specialists and basic immunologists using newly developed transgenic models to dissect the response.
Basic Mechanisms of Vaccine Efficacy:
This concept will provide support for innovative strategies in vaccine development to establish novel, effective and generalizable principles that would allow application to a variety of antigen systems. The work supported by this concept would define basic principles of vaccine efficacy, as well as translate the wealth of recently acquired basic knowledge of immunological mechanisms into novel strategies for vaccination.
Primary Immunodeficiency Disease Registry:
This concept would use the highly successful Chronic Granulomatous Disease Registry as a paradigm and support a registry for 4-5 additional primary immunodeficiency diseases, which is an under served research area. The objective of this concept is: 1) assist research in this area by improving access of investigators to patients for both basic studies and clinical trials; 2) provide accurate and up to date information useful to clinicians and genetic counselors; 3) improve the access fo affected individuals to the latest therapy; and 4) establish a database which can be used to determine the socioeconomic costs of these diseases.
Regulation of the Immune System:
The objective of this concept is to continue support for research to elucidate the molecular machinery and control of the immune response at all levels. This includes continued support for molecular biological studies on gene expression, gene recombination and interactions among different parts of the immune system to control the overall response to a stimulus. It is expected that continued support of these studies will ensure further progress leading to a better understanding of the immune system.
Direct vs. Indirect Antigen Recognition:
The objective of this concept is to continue support for research to elucidate the molecular machinery and control of the immune response at all levels. This includes continued support for molecular biological studies on gene expression, gene recombination and interactions among different parts of the immune system to control the overall response to a stimulus. It is expected that continued support of these studies will ensure further progress leading to a better understanding of the immune system.
Immunological Aspects of Hematopoietic Stem Cell Development:
This concept will support basic studies focused on delineating integral stages in the differentiation of hematopoietic stem cells, in order to advance understanding of the genesis of the immune system from stem cells to progenitor cells and precursor cells of specific lymphoid/myeloid lineages in both human and animal systems.
Mucosal Immunity: Mechanisms and Regulation:
The overall goal of this concept is to support increased investigator-initiated basic and preclinical research into the regulation of the mucosal immune system, including the gut, respiratory, reproductive, and genitourinary mucosa, with their specialized lymphoreticular structures and cells. Research to be supported also encompasses the secretion and transport of IgA and protein natural antibiotics, including the defensins, by mucosal surfaces for host defense and studies that focus on the pathogenesis of diseases related to dysregulation of this system.
Three-Dimensional Structures of Immunological Proteins:
This concept will support basic studies to define the three dimensional structures of proteins that play important roles in initiating and regulating immune responses in both human and animal systems. The objective of this concept is to advance basic understanding of the structural parameters that contribute to the functional activity of immunologically relevant proteins. This information is necessary for the rational design of therapeutic agents that may be used to intervene in immune responses.
Immunological Basis of Food Allergy:
This concept will support research on: (a) the mechanisms of mucosal immunity, and of tolerance as they apply to food allergy; and (b) the molecular identification of food allergens and their epitopes. The results of this research will be used to develop strategies to prevent and treat food allergic patients.
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