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Robert J. Shmookler Reis, DPhil Professor of Geriatrics, Medicine, Biochemistry/Molecular Biology, and Pharmacology/Toxicology Kodetthoor Bhaskara Udupa Chair of Gerontologic Research |
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Doctoral DegreeUniversity of Sussex, Brighton, England, UK, DPhil., Genetics Postdoctoral Training University of California at San Diego, Molecular Genetics MRC Mammalian Genome Unit, Edinburgh, UK, Molecular Genetics McMaster University, Hamilton, Ontario, Canada, Molecular Genetics Research Interests Molecular genetics in aging, cancer, and osteoporosis
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| Molecular genetics of aging, cancer and osteoporosis | ||
| Elevated recombination predisposes cells to cancer initiation and progression. We were the first to note markedly increased levels of homologous recombination, and of expression for Rad51 recombinase, in all cancer cells and other immortal cell lines relative to normal diploid cells. Homologous recombination is elevated in cells transformed by several oncogenes, and in normal cells exposed to known carcinogens (concordance = 1.0). Cancer cells, either cultured in vitro or primary cells from patients, show markedly elevated recombination, expression of recombination-complex genes, loss of heterozygosity, and acquisition of drug resistance, relative to normal control cells.
Genes governing bone density in mice and humans. Genetic loci causing natural variation in bone density were mapped using mouse interstrain crosses. By scanning the genome for linkage to genetic variation in bone density, 5 chromosome regions were identified with significant effects on spinal bone density at maturity, and two impact post-maturity change in bone density. Backcrossed lines of mice, retaining a short segment of "donor" strain genome in a "recipient" strain's genetic background, are then tested for affected bone traits. A human region, corresponding to a mouse "post-maturity change" locus, is significantly associated with spinal BMD in post-menopausal women. Metabolic indices of longevity. We recently began work under an NIH program project grant to identify common metabolic profiles, including markers of oxidative damage and antioxidant defenses, that predict future longevity in young adults of four taxa (yeast, nematodes, insects, and mice). In each model system, we will compare normal-life-span controls to groups with extended life span due to genetic or dietary alteration. Genes regulating longevity in the nematode, C. elegans. We identified a dozen loci with very marked and significant effects on life span, comprising one-third of all such genes with similar effect. Four loci have been isolated in a contrasting, uniform genetic background, and the donor regions have been narrowed and fine-mapped. These loci cause natural variation in life span and specific stress resistances, differing among the four regions. | ||
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