Faculty

Arthur H Tatum, M.D.

Associate Professor, Pathology
8305 Weiskotten Hall
Upstate Medical University
750 East Adams Street
Syracuse, NY 13210
(315) 464-6781

Education and Clinical Training

Ph.D.: 1976, Duke University
M.D.: 1977, Duke University
Residency: 1980, Duke University Medical Center

Clinical Specialty

Anatomic Pathology, Certified: 1981
Clinical Pathology, Certified: 1981

Clinical Department/Section Affiliations

Pathology/Anatomic Pathology

Research Program and Department Affiliations

Pathology

Research Interests

Monoclonal antibody-mediated demyelination; molecular and cell biology of neural cell ashesion molecules

Research Abstract

Pathogenesis of Demyelination by Human Monoclonal IgM reactive with Myelin-associated Glycoprotein (MAG).

IgM paraprotein associated neuropathies in humans are fascinating syndromes because they offer the possibility to study pure antibody mediated nerve damage produced by human monoclonal antibodies. Several problems have prevented the previous development of animal models of this disease:

Human anti-myelin paraproteins have a restricted species specificity that does not include rodents.
The blood nerve barrier is not usually permeable to IgM antibodies that are large molecules (900,000 KD).

This laboratory has recently resolved these problems by developing an avian model system in which systemic passive transfer of IgM anti-MAG paraprotein produces a demyelinating neuropathy that resemble that of the IgM donor. The long term objectives of this laboratory are to understand the mechanism of IgM anti-MAG mediated demyelination, and the functions of the myelin antigens recognized by these antibodies. these objectives are being explored by a combination of in vivo experiments, as well as the use of tissue culture myelinating dorsal root ganglia. Immunohistochemical studies at the light and EM levels, are also being combined with in situ hybridization and other molecular biological approaches. These studies should provide better understanding of myelination and Schwann cell biology, and human paraprotein neuropathies, and to provide insight on other human demyelinating syndromes associated with antibodies to myelin antigens, including Guillian-Barre syndrome, chronic relapsing inflammatory polyneuropathy, and multiple sclerosis. This investigation will also provide new information about the characteristics of targets in the nervous system susceptible to immunological attack.

It is likely that the antigen recognized in vivo is the fascinating molecular myelin-associated glycoprotein. MAG is an intrinsic membrane protein of myelinating Schwann cells, that belongs to the immunoglobulin gene superfamily, and is recognized as a cell adhesion molecule that shares the most homology with NCAM. MAG is present in the periaxonal space where it is thought to be important for axon-Schwann cell interactions, and maintenance of the periaxonal space. MAG is also found to be concentrated in all areas of uncompacted myelin, including: Schmidt-Lanterman incisures, nodes of Ranvier (paranodal myelin), and inner and outer mesaxons, but is not present in compact myelin. The N-terminal of MAG contains the tripeptide sequence Arg-Gly-Asp (RGD) which has been shown to be important in mediating interactions between transmembrane and extracellular proteins. The cytoplasmic domain of MAG is about 100 amino acids containing proteolytic cleavage and phosphorylation sites, and is homologous to the cytoplastic segment of integrin, a transmembrane protein linked to actin. Our studies in which MAG function is perturbed by a monoclonal antibody should provide better understanding of the role of MAG in the myelination process.

Selected References

Khurana KK. Singh SB. Tatum AH. Schulz V. Badawy SZ. Institution, Journal of Reproductive Medicine. 44(6):487-92, 1999 Jun.

Mathur, S.C., Squiers, E.C., Tatum, A.H., Szmalc, F.S., Daucher, J.W., Welker, D.M., and Shanley, P.F. Adenovirus infection of the renal allograft with sparing of pancreas graft function in the recipient of a combined kidney-pancreas transplant. Transplantation 65(1):138-141, 1998

Graziano SL. Kern JA. Herndon JE. Tatum A. Brisson ML. Memoli V. Sugarbaker D. Skarin AT. Kreisman H. Green MR. Analysis of neuroendocrine markers, HER2 and CEA before and after chemotherapy in patients with stage IIIA non-small cell lung cancer: a Cancer and Leukemia Group B study. Lung Cancer. 21(3):203-11, 1998 Sep.

Mehdi SA. Tatum AH. Newman NB. Imperato A. Daucher J. Kohman LJ. Graziano SL. Prognostic significance of Lewis y antigen in resected stage I and II non-small cell lung cancer. Chest. 114(5):1309-15, 1998 Nov.

Uner AH. Tatum AH. Knupp CJ. Gavalchin J. Characteristics of auto anti-idiotypic antibodies reactive with antibodies expressing the pathogenic idiotype, IdLNF1, in the (NZB x SWR)F1 model for lupus nephritis and its parental strains. Journal of Autoimmunity. 11(3):233-40, 1998 Jul.

Colombo, E., Banki, K., Tatum, A.H., Daucher, J., Ferrante, P., Murray, R.S., Phillips, P.E., and Perl, A. Comparative Analysis of Antibody and Cell-mediated Autoimmunity to Transaldolase and Myelin Basic Protein in Patients with Multiple Sclerosis. Journal of Clinical Investigation 99(6):1238-1250, 1997.

This profile was last updated on 05/19/2009

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