Robert J. S. Reis, D. Phil., is a Professor in the UAMS departments of Geriatrics, Medicine, Biochemistry/Molecular Biology, and Pharmacology/Toxicology. He has studied mechanisms underlying aging and longevity, through assessment of DNA methylation, genomic instability, homologous recombination, telomere maintenance, and gene localization.

His cancer-related research has focused on homologous recombination and telomerase activity in normal vs. transformed cells. Dr. Reis’s group was the first to note markedly increased homologous recombination in immortal cell lines, relative to normal human strains, suggesting that high recombination may be a marker of, or predispose toward, cell transformation to immortality. They also discovered that inhibitors of telomerase, and of telomere-telomerase interaction, render immortal cell lines “mortal” — reducing telomere length and growth potential, and inducing apoptosis, in treated fibroblastoid and myeloma cells.

Research on the genetics of aging and life span has utilized gene mapping approaches to define genes affecting longevity, stress resistance, and age-associated diseases. Dr. Reis’s group first mapped chromosomal loci that govern longevity in a genetically heterogeneous population of the nematode C. elegans. They positioned 13 longevity loci and several affecting each of 5 additional traits: resistance to heat shock, ultraviolet radiation, hydrogen peroxide, and volatile anesthetics; and Darwinian fitness. The implicated intervals are being progressively reduced in recombinants, one of them to just 22 established genes, with their spans determined by a novel high-throughput mapping procedure. In an effort to define genes contributing to bone strength, his group mapped gene regions responsible for variation in bone density in mouse interstrain crosses. By scanning the genome for locations cosegregating with bone density, 5 highly-significant genetic regions were identified that govern mature spinal bone density in mice, and another two regions affect post-maturity change in bone density. A human region was identified that corresponds closely to a mouse “post-maturity change” locus, and was found to be associated with spinal BMD in post-menopausal female subjects.

Selected Publications:

Shmookler Reis RJ and Ebert RH II, Animal models for discovery and assessment of genetic determinants of osteoporosis. Osteoporosis Intl. 14(S5):100–106, 2003.

Shammas MA, Shmookler Reis RJ, Akiyama M, Koley H, Chauhan D, Hideshima T, Goyal RK, Hurley LH, Anderson KC, Munshi NC. Telomerase inhibition and cell growth arrest by G-quadruplex interactive agent in multiple myeloma. Mol. Cancer Ther. 2:825–833, 2003.

Shammas MA, Liu X-H, Gavory G, Raney KD, Balasubramanian S, and Shmookler Reis RJ, Targeting the single-strand G overhang of telomeres with PNA inhibits cell growth and induces apoptosis of human immortal cells. Exper. Cell Res. 295: 204–214, 2004.