Robert E. Hughes, Ph.D., Assistant Professor

Molecular and chemical biology of neurodegeneration and aging

The Hughes lab uses a diverse range of technologies to address questions relevant to human disease, aging and therapeutic development. In the area of neurodegeneration, the Hughes lab is primarily interested in discovering and validating molecular targets relevant to Huntington’s disease (HD).

In the past year it has published a major work on protein interactions in HD and how interacting proteins can be exploited as drug targets. The lab continues to validate these targets in more complex disease models. It has also completed a genome-scale screen using RNAi, short sequences of RNA which can silence gene expression, against a cell-based model of HD and is currently studying molecular hits from these screens in more complex validation models.

Finally, the Hughes lab is studying novel small molecule inhibitors of HD toxicity for development as therapeutic treatments. The Hughes lab also has a major emphasis on using yeast genetics and biochemistry to study questions relevant to human health. In this regard, two main projects in aging research are ongoing: In the small molecule discovery project, a large chemical library is being screened to identify compounds that can extend yeast lifespan. Promising compounds will be investigated as potential therapeutics for age-related disease.

Using yeast genetic technology, the lab has also developed a genome-scale protein interaction network for human proteins implicated in longevity. Proteins in this network are being validated for authentic roles in longevity using a nematode model of lifespan. Finally, the Hughes lab conducts stem cell research with an emphasis on chemical discovery. The lab is designing assays to identify small molecules that can influence and direct the growth and development of stem cells. Hits from these screens can potentially be developed into therapeutic compounds in regenerative medicine applications.

“These data taken together indicate we may have gotten our hands on a fairly significant number of genes that modify Huntington’s disease in humans.” 

—Dr. Robert Hughes, quoted in the Marin Independent Journal