Autoimmunity and Neuroendocrinology

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 (Notkins, A.L.: Scientific American, 296, 72-9, 2007).

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 secretory vesicles (dense core and synaptic). These proteins are present in most of the neuroendocrine cells in the body. Knockout, knockdown, and overexpression experiments have shown that these proteins affect the secretion of hormones and neurotransmitters. Current studies are concerned with the effect of IA-2 and IA-2ß on secretion and how this, in turn, alters behavior, learning, circadian rhythm, and the immune system (Harashima, S, et al.: Proc. Natl. Acad. Sci. USA, 102, 8704-8709, 2005; Nishimura, T.: Neuroscience, 159, 427-437, 2009; Kim, S. M.: The FASEB Journal, 23, 3226-3232, 2009).

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 and regulate polyreactive antibodies also are under investigation (Notkins, A.L.:Trends in Immunol, 25,174-179, 2004; Zhou,Z-H, et al.: Cell Host & Microbe, 1, 51-61, 2007).

Applicants must have a Ph.D., M.D., or equivalent with experience in cellular immunology and/or neuroendocrinology. To apply, click on the button below, or send your CV with cover letter to:

Abner Louis Notkins, M.D.
Chief, Experimental Medicine Section
NIDCR, NIH
Building 30, Room 106
30 Convent Drive
Bethesda, Maryland 20892, USA
E-mail: anotkins@mail.nih.gov
Telephone: (301) 496-4535


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