Over the last year the laboratory has focused on two areas. The first concerns the properties and function of IA-2 and IA-2 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) and neurotransmitters. Current studies are concerned with the effect of IA-2 and IA-2 on the secretion of these hormones and neurotransmitters and how, in turn, they affect a variety of physiologic processes. The second area concerns 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.

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National Institute of Dental & Craniofacial Research
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Cai, Tao; Notkins, Abner L (2016) Pathophysiologic changes in IA-2/IA-2? null mice are secondary to alterations in the secretion of hormones and neurotransmitters. Acta Diabetol 53:7-12
Burbelo, Peter D; Lebovitz, Evan E; Notkins, Abner L (2015) Luciferase immunoprecipitation systems for measuring antibodies in autoimmune and infectious diseases. Transl Res 165:325-35
Cai, Tao; Hirai, Hiroki; Xu, Huanyu et al. (2015) The minimal promoter region of the dense-core vesicle protein IA-2: transcriptional regulation by CREB. Acta Diabetol 52:573-80
Gunti, Sreenivasulu; Notkins, Abner Louis (2015) Polyreactive Antibodies: Function and Quantification. J Infect Dis 212 Suppl 1:S42-6
Pfeifer, C R; Shomorony, A; Aronova, M A et al. (2015) Quantitative analysis of mouse pancreatic islet architecture by serial block-face SEM. J Struct Biol 189:44-52
Gunti, S; Kampylafka, E I; Tzioufas, A G et al. (2015) Polyreactive antibodies in the circulation of patients with systemic lupus erythematosus. Lupus 24:1567-9
Shomorony, A; Pfeifer, C R; Aronova, M A et al. (2015) Combining quantitative 2D and 3D image analysis in the serial block face SEM: application to secretory organelles of pancreatic islet cells. J Microsc 259:155-64
Abuhatzira, Liron; Xu, Huanyu; Tahhan, Georges et al. (2015) Multiple microRNAs within the 14q32 cluster target the mRNAs of major type 1 diabetes autoantigens IA-2, IA-2?, and GAD65. FASEB J :
Xu, Huanyu; Abuhatzira, Liron; Carmona, Gilberto N et al. (2015) The Ia-2? intronic miRNA, miR-153, is a negative regulator of insulin and dopamine secretion through its effect on the Cacna1c gene in mice. Diabetologia 58:2298-306
Qiu, Qi; Xu, Zhili; Tian, Jie et al. (2015) Impact of natural IgM concentration on gene therapy with adenovirus type 5 vectors. J Virol 89:3412-6

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