Abner Louis Notkins, M.D.
Laboratory of Sensory Biology/Experimental Medicine Section
Building 30, Room 106
30 Convent Drive
Bethesda, MD 20892
Autoimmune Diabetes and Immunology
The laboratory is focusing on three related areas:
- The first is concerned with the identification of new autoantigens, the autoantibodies with which these autoantigens react and the value of autoantibodies in predicting the development of autoimmune diseases. The long term goal is to define the human 'autoantigenome' – that is the identification and characterization of the major autoantigens in the most common human autoimmune diseases – by high throughput procedures and extensive screening of the proteome.
- The second area concerns the properties and function of IA-2 and IA-2ß which are major autoantigens in type 1 diabetes and transmembrane proteins of dense core secretory vesicles. These proteins are present in most of the neuroendocrine cells in the body. Knockout and knock down technology has shown that these proteins affect the secretion of hormones (e.g., insulin). Current studies are concerned with the effect of IA-2 and IA-2ß on the secretion of neurotransmitters and how this, in turn, alters behavior, learning and life-span.
- The third area involves polyreactive antibodies. Hybridoma technology has shown that many antibody molecules are polyreactive – that is, they can bind to a variety of different and structurally unrelated self and non-self foreign antigens. These antibodies generally have low binding affinity and are encoded by germ-line or near germ-line sequences. Further studies revealed that much of the natural antibody repertoire is made up of polyreactive antibody. The function of the natural antibody repertoire has remained an enigma. Current studies are focusing on the role of polyreactive antibodies in: defense against foreign organisms (i.e., bacteria/viruses); the clearance of damaged proteins and cells; and the possible role of these antibodies in the induction and/or maintenance of immunological tolerance. The cells that make polyreactive antibodies also are under investigation.
- B.A., Yale University
- M.D., New York University
- House Staff (internal medicine), Johns Hopkins Hospital
Xu H, Abuhatzira L, Carmona GN, Vadrevu S, Satin LS, Notkins AL. The Ia-2β intronic miRNA, miR-153, is a negative regulator of insulin and dopamine secretion through its effect on the Cacna1c gene in mice. Diabetologia. 2015;58(10):2298-306.
Abuhatzira L, Xu H, Tahhan G, Boulougoura A, Schäffer AA, Notkins AL. Multiple microRNAs within the 14q32 cluster target the mRNAs of major type 1 diabetes autoantigens IA-2, IA-2β, and GAD65. FASEB J. 2015;29(10):4374-83.
Sun C, Tian X, Lee YS, Gunti S, Lipsky A, Herman SE, Salem D, Stetler-Stevenson M, Yuan C, Kardava L, Moir S, Maric I, Valdez J, Soto S, Marti GE, Farooqui MZ, Notkins AL, Wiestner A, Aue G. Partial reconstitution of humoral immunity and fewer infections in patients with chronic lymphocytic leukemia treated with ibrutinib. Blood. 2015;126(19):2213-9.
Chen C, Notkins AL, Lan MS. Insulinoma-Associated-1: From Neuroendocrine Tumor Marker to Cancer Therapeutics. Mol Cancer Res. 2019;17(8):1597-1604.
Related Scientific Focus Areas
Genetics and Genomics
This page was last updated on August 19th, 2019