My research focuses on the molecular genetics of longevity and age-associated diseases. I was trained in genetics, and turned to C. elegans as a model system in which to define and characterize genes that govern longevity. Using novel gene-mapping methods we developed, we discovered over 27 highly-significant loci for lifespan, resistance to stresses, and Darwinian fitness. Using chromosomal fine-mapping, we identified one longevity gene as REC-8, a meiotic cohesin that helps hold tetrads together and was thought to be silent in mitotic cells. However, we showed that it actually makes somatic tissues more vulnerable to diverse stresses, while stabilizing the meiotic genome, and its depletion in C. elegans or knockout in haploid yeast increases lifespan. My group was the first to identify the Pirin gene on the human X chromosome as a regulator of post-menopausal bone loss in women, a discovery confirmed in a Chinese population. We also pioneered the role of homologous recombination in the development and progression of myeloma, prostate, and breast cancers. We were the first to note that cells from many different cancer types feature very high levels of homologous recombination, and high expression of the Rad51 recombinase complex that mediates it. We are now working chiefly on genetic factors that regulate lifespan, and that contribute to protein aggregates — key toxic intermediates in neurodegenerative diseases. We have identified proteins in specific aggregate types that are highly enriched in Alzheimer’s cortex, and many of them play functional roles in aggregate formation in C. elegans models. Their toxic effects turn out to be mediated in large part by blockage of proteasomes and autophagosomes. We are combining exploratory proteomics and immunochemistry in human cortex and cultured neurons, with the facile genetics of nematodes, to better understand how aggregates begin, grow, and ultimately disrupt proteostasis.