Terence E. Martin, Ph.D.

The Role of Nuclear and Cytoplasmic Ribonucleoprotein Complexes in the Processing and Transport of RNA; Functional Domains of the Cell Nucleus; Effect of Viruses

Research Summary

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.

Selected Papers

Storb U, Peters A, Kim N, Shen HM, Bozek G, Michael N, Hackett J Jr, Klotz E, Reynolds JD, Loeb LA and Martin TE. (1999). "Molecular aspects of somatic hypermutation of immunoglobulin genes." Cold Spring Harb Symp Quant Biol 64: 227-34.

Pellicciari C, Bottone MG, Scovassi AI, Martin TE 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.

Kopecny V, Biggiogera M, Pivko J, Pavlok A, Martin TE, Kaufmann SH, Shaper JH and Fakan S. (2000). "Fine-structural cytochemical and immunocytochemical observations on nuclear bodies in the bovine 2-cell embryo." Zygote 8: 315-28.

Michael N, Martin TE, 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.

Soldani C, Bottone MG, Biggiogera M, Alpini C, Scovassi AI, Martin T and Pellicciari C. (2002). "Nuclear localization of phosphorylated c-Myc protein in human tumor cells." Eur J Histochem 46: 377-80.

Kim N, Martin TE, Simon MC and Storb U. (2003). "The transcription factor Spi-B is not required for somatic hypermutation." Mol Immunol 39: 577-83.

Martin TE, Powell CT, Wang Z, Bhattacharyya S, Walsh-Reitz MM, Agarwal K and Toback FG. (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.

Toback FG, Walsh-Reitz MM, Musch MW, Chang EB, Del Valle J, Ren H, Huang E and Martin TE. (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

Vazquez-Nin GH, Echeverria OM, Ortiz R, Scassellati C, Martin TE, 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. 69:1362-1370.

Malatesta M, Scassellati C, Fakan S, Meister G, Plottner O, Buehler D, Sowa G, Martin TE and Fischer U. (2004). Ultrastructural characterisation of a nuclear domain highly enriched in survival of motor neuron (SMN) protein. Exp. Cell Res. 292:312-321.

Fraschini A, Bottone MG, Scovassi AI, Denegri M, Risueno MC, Testillano PS, Martin TE, Biggiogera M and Pellicciari C. (2005). Changes in extranucleolar transcription during actinomycin D-induced apoptosis. Histol Histopathol. 20(1):107-17.