Robert Hughes, PhD, Associate Professor

Understanding the mechanisms of aging and neurodegeneration in healthy adults and in people with disorders such as Huntington’s disease

Dr. Hughes recently collaborated with Buck Institute colleague Dr. Lisa Ellerby to find new targets for potential drug therapies in HD, a progressive genetic disease that destroys nerves, impairs movement, and causes cognitive decline.   Dr. Hughes and his team members discovered that a set of enzymes implicated in stroke and cancer may also advance HD.  These enzymes contribute to nerve toxicity by producing harmful fragments from the breakdown of a molecule characteristic of the disease, a mutant form of the huntingtin protein (Htt).   Dr. Hughes was a co-author of a paper about this research that appeared as a 2010 cover story in the prestigious scientific journal Neuron.

The Hughes lab explores mechanisms of aging and searches for drug targets through a broad array of methods, including protein analysis, chemical screening, and disease models in yeast.  His research on the pathways of normal aging addresses one of the Buck Institute’s primary goals – extending not only the human lifespan but also the number of healthy years – the “healthspan.’’   Dr. Hughes is investigating the systems that maintain the ability of proteins to fold into the shapes that best support healthy functioning.  This optimal protein folding is compromised in both aging and disease.  The Hughes lab is screening for compounds that help preserve protein configurations in aging yeast cells, which can provide clues on similar functions in human cells.

Dr. Hughes received his PhD in Biology from Yale University.  He completed postdoctoral fellowships in the departments of Biochemistry and Genome Sciences at the University of Washington in Seattle, where he worked in the laboratory of Stanley Fields, PhD, a pioneer in yeast technology.  As an Assistant Professor in the Division of Medical Genetics, Department of Medicine at the UW Medical School, Dr. Hughes developed yeast-based models of human genetic disorders, including Huntington’s disease (HD).  He was Director of Therapeutic Biology at Prolexys Pharmaceuticals in Salt Lake City, Utah before he joined the Buck Institute in 2005. Dr. Hughes also holds an MA in English and Comparative Literature from Columbia University.

rhughes@buckinstitute.org
Phone: 415-209-2069
Administrative Lab Coordinator: Libbie Butler
lbutler@buckinstitute.org
Phone: 415-493-3675

“My hope is that the work in my lab leads to a successful treatment for Huntington’s disease and also informs the field of age research and the onset of late onset disease.”

- Robert Hughes, PhD

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Recent Publications

2014

Cendrine Tourette, Biao Li... Robert E Hughes "A Large-scale Huntingtin Protein Interaction Network Implicates Rho GTPase Signaling Pathways in Huntington's Disease." J. Biol. Chem. Epub ahead of print
Adam L Orr, Deepthi Ashok... Martin D Brand "Novel Inhibitors of Mitochondrial sn-Glycerol 3-phosphate Dehydrogenase." PLoS ONE 9:2 e89938
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