Dr. Robert Reis
University of Arkansas, Professor of Geriatrics, Biochemistry/Mol.Biol., and Pharmacology
Robert J. S. Reis, D. Phil., is a molecular geneticist with extensive experience in and the genetics of longevity, epigenetics, genomic instability, gene mapping, and the role of homologous recombination in cancer progression. He received his B.A. from Harvard University and D. Phil. in Genetics from Sussex University (U.K.), and trained as a postdoctoral fellow in the MRC Mammalian Genome Unit in Edinburgh and at UCSD, La Jolla. He has been the mentor of 17 Ph.D. students and 16 postdoctoral fellows at UAMS, and has mentored junior faculty at both UAMS and the VAMC. Dr. Reis’s research interests currently include analyses of longevity mutants in C. elegans by genomic, transcriptomic, metabolomic and proteomic approaches; cancer mechanisms and therapies; and shared mechanisms underlying neurodegenerative diseases.
Tenfold increase in worm longevity: What’s in it for YOU? We reported in 2008 that worms could live 10 times their normal lifespan if they had a severe mutation in the “age-1” gene. This gene encodes an enzyme responsible for making PIP3, a molecule that tethers many enzymes to the inner cell membrane, where they are poised to interact with other enzymes in the same signaling pathway. The mutant worms that live extraordinarily long have no detectable PIP3, and most of their signaling pathways are silenced.
This is okay if you are living in a Petri dish with plentiful food and no bacteria or viruses. But we humans need dividing cells to fight infections, and one of the silenced pathways is needed for cell division! How could we benefit from what we found in the longest-lived mutants ever discovered, without being ravaged by diseases (or becoming worms)?
We decided to look beyond the mutated gene, to learn which proteins depend on its product, PIP3. Using an approach that combines proteomics and genetics, we discovered 81 proteins that have to bind PIP3 to do their jobs properly. We tested the effect of “knocking down” 6 of those, and confirmed that for at least 5 of them, worms with less of that protein lived longer and resisted stresses better.
So we think we have developed a novel method to discover new drug targets that together should extend human lifespan (maybe 10-fold, probably something a bit less dramatic!), while avoiding the unpleasant consequences of halting cell division.