My current research interests are all related to the application of genetic concepts and methodologies to the elucidation of the pathobiology of aging in man, other mammals, and birds. There are three broad areas of concentration. 1) The genetic basis forsusceptibility and resistance to dementias of the Alzheimer type. The major current initiative is the use of the yeast protein interaction trap (two hybrid system) for the discovery of cDNAs that code for proteins interacting with domains of the betta amyloid precursor protein; these would be candidates for new genes of relevance to the pathogenesis. 2) The nature of gene action in the pathogenesis of Werner syndrome, a rare autosomal recessive with striking progeroid features. Clinical pathological and genetic studies are expedited by the establishment of an International Registry of Werner Syndrome in our laboratory. 3) Together with several colleagues at the University of Washington, we are investigating DNA damage associated with aging. The approachesinclude the synthesis of cell lines and transgenic mice exhibiting resistance to mutagenesis mediated by oxidative damage. These studies also address genetic mechanisms underlying the unusual resistance of certain avian species to oxidative damage.

Selected Publications:

Guo, Q., Fu, W., Sopher, B., Miller, M.W., Ware, C.B., Martin, G.M., Mattson, M.P. Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in mice. Nat Med 5(1):101-106, 1999.

Hu, Q., Kukull, W.A., Bressler, S.L., Gray, M.D., Cam, J.A., Larson, E., Martin, G.M., Deeb, S.S. The human FE65: genomic structure and an intronic bi-allelic polymorphism associated with sporadic dementia of the Alzheimer type. Hum Genet 103:295-303, 1998.

Martin, G.M. Genetics and aging. In: The Metabolic and Molecular Bases of Inherited Disease, Vol. 1, 8th edition, Scriver, C.R., Beaudet, A.L., Sly, W.S., Valle, D., eds. McGraw-Hill Pub. Co., New York, NY, pp 215-223, 2001

Feng, R., Rampon, C., Tang, Y., Shrom, D., Jin, J., Kyin, M., Sopher, B., Martin, G.M., Kim, S., Langdon, R.B., Sisodia, S.S., and Tsien, J.Z., Deficient Neurogenesis in Forebrain-Specific Presenilin-1 Knockout Mice is Associated with Reduced Clearance of Hippocampal Memory Traces. Neuron. 32: 911-926, 2001.

Hu, Q., Cool, B.H., Wang, B., Hearn, M.G., and Martin, G.M. A Candidate Molecular Mechanism for the Association of an Intronic Polymorphism of FE65 with Resistance to Very-Late Onset Dementia of the Alzheimer Type. Human Molecular Genetics. 11: 465-475, 2002.Traces. Neuron. 32: 911-926, 2001.

Martin, G.M. Gene Action in the Aging Brain: An Evolutionary Biological Perspective. Neurobiol Aging, 2002 Sep;23(5):647.

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