Our Research

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Environmental Factors Contributing to Disease

Recently we have been studying how environmental factors can contribute to disease. Our first interest along this line was how various food additives may interact with energy homeostasis and metabolic health, with the hypothesis that some things we eat are responsible for the doubling of metabolic disease observed over the past 30 years. One of our first focuses towards this goal was to experimentally test the impact of various synthetic food additives (assumed to be benign) on energy homeostasis in the fruit fly. Through this we found that in fruit flies, chronic consumption of various artificial sweeteners causes hyperactivity, insomnia, and triggers an increase in food intake. Mechanistically this occurred by upsetting the sweetness vs energy balance of food, and this imbalance was detected via nutritional and energy sensors in the fly brain. Surprisingly, this sweet/energy imbalance triggered direct sensitization of sweet taste neurons to nutritive sugar, and we also observe a similar effect in mice. Using flies, we continue to investigate how environmental factors interact with genetics to promote metabolic disease and neurodegeneration.

 
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Pain

For the last 15 years we have been investigating the conserved genetic framework that allows animals and humans to feel pain. We do this using human genetics data for pain as reference point, followed by various high throughput screening systems in the fruit fly, and then further characterization in mouse systems. Through combining human and fly systems, we have identified hundreds of novel conserved pain genes, and including over 50 new drug targets and dozens of novel transcriptional regulators required for pain neurons to develop.

Moreover, we have developed numerous new assay systems for studying pain in the adult fruit fly, and we couple these new tools with electrophysiology and Calcium imaging in order to find and characterize novel genes, pathways, and neurons involved in pain sensation in the fly. We have also developed multiple new models of chronic pain in the fly, including neuropathic and inflammatory modalities, and continue our efforts to understand how pain states change after injury using these systems. 

 
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Lifespan

We have become interested in what controls an animal’s lifespan, and if its possible to extend lifespan while preserving cognitive function. Again, starting with human genomics information (association or DNA/RNA sequencing), we have targeted hundreds of conserved neuronal genes and pathways looking for lifespan extension effects in the fly. From this effort we have identified ~40 new genes that when targeted can extend lifespan, some of can also preserve cognitive function in aged animals. We continue to investigate these new genes, placing them in existing lifespan pathways or in some cases what appear to be completely novel organ-specific lifespan regulating pathways.