The overall emphasis of research in this laboratory is in human T- and B-cell development and in aberrations in their development and regulation. The work involves three particular areas of investigation: 1) the human primary immunodeficiency diseases; 2) human thymic education; and 3) regulation of human IgE synthesis. Methodology includes monoclonal antibody analyses of lymphocyte phenotypes, a variety of T-cell and NK cell functional assays, T-cell cloning, analysis of defects in T-cell signaling, and assessment of B-cell differentiation through measurement of immunoglobulin synthesized and secreted into supernatants of cultured blood mononuclear cells (MNC). This laboratory was the first to measure human IgE synthesis by cultured blood MNC. A highly reproducible system of studying IgE synthesis in vitro was discovered in this laboratory and involves use of a special tissue culture medium and recombinant human IL-4 or IL 13, with and without anti-CD4O and/or hydrocortisone. One of the largest (if not the largest) populations of patients with well-defined primary immunodeficiency diseases in this country is available for study. Phenotypic analyses of lymphocytes from the large number of infants with SCII) followed here recently led to the discovery by this laboratory of two previously unidentified molecular defects resulting in the human SCID syndrome, Jak 3 deficiency and IL­7Ra chain deficiency. A major interest in this laboratory over the past seventeen years has been in the developing immune function of human infants with severe combined immunodeficiency disease (SCID) following transplants of HLA­identical or haploidentical (post-thymic T-cell depleted) bone marrow cells. Studies are ongoing examining T- and B-cell ontogeny, the extent of chimerism, the nature of immune cell cooperation between genetically disparate cells, mechanisms of tolerance induction and MHC restriction of genetically dnor T­cells that have been educated in these SCID thymi.

Mary Louise Markert, M.D., Ph.D., Associate Professor of Pediatrics Immunology

Dr. Markert 's laboratory focuses on immunoreconstitution in patients with inherited and acquired forms of immunodeficiency. At present she is working with patients with DiGeorge Syndrome and HIV infection. Infants with DiGeorge syndrome are born with no thymus and have no circulating T-cells. She is developing thymic transplantation for this disorder and are using these clinical experiments to learn about the role of the thymus in postnatal T-cell differentiation.

 

 

 

Dr. Burks’ research is on the characterization of food allergens at the molecular level and on approaches to therapy based on this information. He has pursued this area of research since his fellowship days here at Duke and is currently internationally recognized as one of the top 5 leaders in the world in research in the field of food hypersensitivity. The three areas of focus within his laboratory are to: (1) understand the mechanism of food allergy, (2) improve the diagnosis of food allergy in children, and (3) develop immune therapy for food allergy. Methodology of the laboratory includes in vitro lymphocyte proliferation, analysis of lymphocyte phenotypes, T cell cloning, specific immunoglobulin production, allergen identification, purification, allergen gene cloning and mutation of allergen genes. Dr. Burks has acquired a large cohort of sera and cells from patients with food allergies, such as those to peanut, milk, or egg. Additionally, he has collected longitudinal samples from these patients who have either continued to have their food sensitivity or to have outgrown their food sensitivity.  Studies ongoing currently include those in peanut, milk and egg allergy.  Animal models of peanut allergy have been developed in C3H/HeJ mice.  Studies with immune therapy in this mouse model are ongoing, with the goal being to develop a vaccine to prevent future peanut allergic reactions in already sensitized mice.

 

 

The research of Dr. Frank's laboratory revolves around effector mechanisms of immune damage.  Specifically, the laboratory is interested in understanding how antibody and complement contribute to the damage of tissues and micro-organisms.  Overlapping areas of interest include the role of mediators in inflammation and the functions of antibody and complement in the production of autoimmune disease.  Specific interests of the group in the last year have included studies of the mechanism by which infusion of intravenous immunoglobulin into animals and man down regulates immunologic damage.  It appears that the level of natural antibody regulates the extent of complement mediated tissue damage.  Evidence has been presented that one function of intravenous immunoglobulin is to prevent complement attack on targets.  The group is interested in understanding the mechanisms of these effects.  Specifically, they are examining the role of class of immunoglobulin, fragment of antibody and mechanism of action of intravenous immunoglobulin.  The second major project involves study of complement in xenograft rejection.  The focus of the project is on mechanisms by which xenografts undergo hyperacute rejection. Hyperacute rejection is known to depend on complement activation leading to the destruction of the grafted tissues.  The laboratory is attempting to develop methods for prevention of hyperacute graft rejection and is attempting to understand the mechanisms by which complement limits the life of grafts.  Other aspects of complement and antibody function in the production of human disease are under investigation.