Completed and Ongoing Projects in the Sutphin Lab
Sutphin Lab experimental pipeline. Our formal experimental pipeline uses tools in systems and comparative genetics to: 1. generate lists of candidate aging genes from available human data, 2. apply lifespan screening in C. elegans to select the most promising candidates, 3. use molecular tools in C. elegans to build mechanistic models describing the role of selected candidate genes in aging, 4. validate these models in mice, and 5. translate validated models to develop novel clinical interventions.
Projects are broken down by their place in the our comparative genetics pipeline (Figure 1).
1. Candidate Generation
- Identification of human genes deferentially expressed with age in blood via gene expression meta-analysis of CHARGE datasets
- Aging candidates from mammalian longevity GWAS meta-analysis
- Selection of genes highly represented in aging gene sets using Gene Weaver
2. Candidate Selection
- C. elegans longevity screen of CHARGE genes differentially expressed with age in human blood
- Survey of kynurenine pathway genes and metabolites for longevity regulators
- C. elegans longevity screen of serpin genes
- C. elegans longevity screen of tetraspanin genes
Projects developing related tools:
- WORMHOLE ortholog prediction using machine learning
- Robotic systems for automated worm lifespan measurement
3. Molecular Characterization
- Investigation of molecular mechanisms linking HAAO and 3HAA to aging in C. elegans
- Investigation of molecular mechanisms linking KYNU to aging in C. elegans
- Evaluation of HAAO inhibition and 3HAA supplementation as interventions in C. elegans models of proteotoxicity and neurodegeneration
4. Validation
- Evaluation of HAAO inhibition and 3HAA supplementation as interventions to extend lifespan and delay tissue-specific aging in mice
- Evaluation of HAAO and 3HAA as intervention targets in mouse models of Alzheimer’s disease
- Evaluation of 3HAA supplementation as a stroke recovery treatment
5. Translation
Other Projects
- Investigation of molecular mechanisms of lifespan extension by caffeine in C. elegans
- Evaluation of the anti-aging effects of caffeine in mice