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Abner Louis Notkins, M.D.

Abner Louis Notkins, M.D.Chief, Experimental Medicine Section
Laboratory of Sensory Biology

NATIONAL INSTITUTES OF HEALTH/NIDCR
BUILDING 30 ROOM 106
30 CONVENT DR, MSC 4352
BETHESDA MD 20892-4352

Phone: (301) 496-4535
Fax: (301) 402-4163
E-mail: anotkins@mail.nih.gov

Biographical Sketch

  • B.A., Yale University
  • M.D., New York University
  • House Staff (internal medicine), Johns Hopkins Hospital

Research Interests/Scientific Focus

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.

Selected Publications

  1. Zhou, Zhao-Hua, Zhang, Y, Hu, Y, Wahl, L.M., Cisar, J.O., Notkins, A.L.: 2007. The Broad Antibacterial Activity of the Natural Antibody Repertoire is Due to Polyreactive Antibodies. Cell Host & Microbe, 1, 51-61. http://www.ncbi.nlm.nih.gov/pubmed/18005681
  2. Notkins, A.L.: 2007. New Predictors of Disease. Scientific American 296, 72-9 (Cover   Story). http://www.ncbi.nlm.nih.gov/pubmed/17348162
  3. Cai T, Hirai H, Fukushige T, Yu P, Zhang G, Notkins AL, Krause M. Loss of the transcriptional repressor PAG-3/Gfi-1 results in enhanced neurosecretion that is dependent on the dense-core vesicle membrane protein IDA-1/IA-2. PLoS Genet. 2009 Apr;5(4):e1000447. Epub 2009 Apr 3. http://www.ncbi.nlm.nih.gov/pubmed/19343207
  4. Kim SM, Power A, Brown TM, Constance CM, Coon SL, Nishimura T, Hirai H, Cai T, Eisner C, Weaver DR, Piggins HD, Klein DC, Schnermann J, Notkins AL. Deletion of the secretory vesicle proteins IA-2 and IA-2beta disrupts circadian rhythms of cardiovascular and physical activity. FASEB J. 2009 Sep;23(9):3226-32. Epub 2009 May 11. http://www.ncbi.nlm.nih.gov/pubmed/19433624

  5. Cai T, Hirai H, Zhang G, Zhang M, Takahashi N, Kasai H, Satin LS, Leapman RD, Notkins AL. Deletion of Ia-2 and/or Ia-2β in mice decreases insulin secretion by reducing the number of dense core vesicles. Diabetologia. 2011 Sep;54(9):2347-57. Epub 2011 Jul 6. http://www.ncbi.nlm.nih.gov/pubmed/21732083

 

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This page last updated: May 28, 2014