Faculty
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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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