Dr. Daniel Promislow is interested in genetic variation in patterns of aging in natural populations of several species, including flies, dogs, marmosets and humans. He began his work on aging using comparative approaches to study the evolution of senescence in natural populations of mammals. Since then I have used a variety of approaches in my research, from mathematical modeling and statistical analysis of high-throughput datasets, to demography and epidemiology in domestic dogs, to experimental quantitative genetics in fruit flies. Work in the Promislow lab has been or is currently funded by grants from NIH, NSF, the Ellison Medical Foundation, and the American Federation for Aging Research.
In a UW ADRC project, his lab members are developing the fruit fly as a powerful model to study natural genetic variation for the susceptibility to Aβ and tau-related pathology, and to understand the underlying mechanisms by which these genetic variants influence susceptibility. They are using systems biology approaches in the fruit fly to identify naturally occurring allelic variants that modify the effects of Aβ and tau expression in the fly eye. Currently, they are compiling a full screen of the Drosophila Genome Reference Panel (DGRP)—a mapping population of 200 fully sequenced inbred lines, and they have identified several very promising candidate loci. They will carry out metabolomic profiling to compare strains that are able to ameliorate the effects of Aβ/tau expression with those that cannot. As proof of principle, they have demonstrated that whole-body metabolome profiles are able to fully distinguish strains that are sensitive vs. resistant to the toxic effects of H2O2.
The Promislow Lab team is also carrying out similar studies on the aging metabolome in the common marmoset. They use network analysis to study how large-scale structures of genomic and metabolomics networks change with age, with the goal of identifying novel pathways associated with aging, and of understanding what makes certain pathways robust or susceptible to the aging process.
Evolutionary genetics, Evolutionary metabolomics, Mating behavior and aging in Drosophila, Genetic epidemiology of aging and disease in dogs, Drosophila models of neurodegenerative disease