Current research continues to be
centered on basic mechanisms of gene expression, particularly in
regard to nuclear structure and RNA synthesis and processing; in
this regard we have studied the influence of viruses on the nuclear
protein antigens of autoimmune disease. The reorganization of these
nuclear antigens during normal development and during apoptosis
has also been addressed in collaboration with several European laboratories.
Currently the proteins directly involved in RNA transcription elongation
are under study, and this has led to an active collaboration on
the relationship of transcription to somatic hypermutation of Ig
genes with Ursula Storb
(see recent publications).
Our recent discovery of a novel stomach
protein, expressed only in the lumenal surface epithelial cells,
has led us to initiate a study of this gene in humans and mice.
We have raised high-titer antibodies to the protein and used immuno-electron
microscopy to localize it to secretion granules of mucosal epithelial
cells. Our current studies have demonstrated that it has growth
factor activity; the additional possibility that it can serve as
a precursor of bioactive peptides with a role in innate immunity
in the stomach is being explored. Given the need for rapid replacement
of gastric epithelial cells as a result of the acid environment,
mechanical damage and possible bacterial infiltration it is likely
that this factor is important in the maintenance and restitution
of the stomach epithelium. We propose to analyze the mechanism of
gastric epithelial cell growth stimulation and study the consequences
of a knockout of this gene in mice.
Toback, F. G., Walsh-Reitz, M. M.,
Musch, M. W., Chang, E. B., Del Valle, J., Ren, H., Huang, E. and
Martin, T. E. (2003). "Peptide fragments of AMP-18, a novel
secreted gastric antrum mucosal protein, are mitogenic and motogenic."
Am J Physiol Gastrointest Liver Physiol 285: G344-53. (PubMed)
Vazquez-Nin, G. H., Echeverria, O.
M., Ortiz, R., Scassellati, C., Martin, T. E., Ubaldo, E. and Fakan,
S. (2003). "Fine Structural Cytochemical Analysis of Homologous
Chromosome Recognition, Alignment, and Pairing in Guinea Pig Spermatogonia
and Spermatocytes." Biol Reprod. (PubMed)
Kim, N., Martin, T. E., Simon, M.
C. and Storb, U. (2003). "The transcription factor Spi-B is
not required for somatic hypermutation." Mol Immunol 39: 577-83.
Martin, T. E., Powell, C. T., Wang,
Z., Bhattacharyya, S., Walsh-Reitz, M. M., Agarwal, K. andToback,
F. G. (2003). "A novel mitogenic protein that is highly expressed
in cells of the gastric antrum mucosa." Am J Physiol Gastrointest
Liver Physiol 285: G332-43. (PubMed)
Michael, N., Martin, T. E., Nicolae,
D., Kim, N., Padjen, K., Zhan, P., Nguyen, H., Pinkert, C. and Storb,
U. (2002). "Effects of sequence and structure on the hypermutability
of immunoglobulin genes." Immunity 16: 123-34. (PubMed)
Soldani, C., Bottone, M. G., Biggiogera,
M., Alpini, C., Scovassi, A. I., Martin, T. and Pellicciari, C.
(2002). "Nuclear localization of phosphorylated c-Myc protein
in human tumor cells." Eur J Histochem 46: 377-80. (PubMed)
Pellicciari, C., Bottone, M. G.,
Scovassi, A. I., Martin, T. E. and Biggiogera, M. (2000). "Rearrangement
of nuclear ribonucleoproteins and extrusion of nucleolus-like bodies
during apoptosis induced by hypertonic stress." Eur J Histochem
44: 247-54. (PubMed)