Genetic and environmental risks for autism

Autism prevalence is on the rise and we need to understand why. In a study published in Nature (see also press release), we found that topoisomerase inhibitors reduce the expression of long genes in mouse and human neurons, including a remarkable number of genes implicated in Autism Spectrum Disorders. We also identified a class of fungicides that alter gene transcription in a manner that is strikingly similar to changes seen in the brains of people with autism and neurodegeneration (published in Nat. Comm.).  These studies could uncover environmental contributions to autism, a topic our lab is actively pursuing.  We are also studying several high confidence autism gene mutations, including a hyperactivating autism-linked mutation that we characterized in UBE3A (published in Cell).


Unsilencing Angelman Syndrome

 

Unsilencing of Ube3a in mouse spinal cord after Topotecan administration

Unsilencing of Ube3a in mouse spinal cord after Topotecan administration

Angelman Syndrome is a severe disorder with symptoms that include speech impairment, intellectual disability and seizures. This lifelong disorder profoundly impacts patients and their families, yet no effective treatment currently exists. It is well established that this disorder is caused by genetic alterations in the maternally-inherited copy of a gene called Ube3a.

In collaboration with Drs. Ben Philpot and Bryan Roth, we found that topoisomerase inhibitors unsilence a dormant but functional copy of Ube3a in mice. We aim to advance our understanding of how these drugs work, with the ultimate goal of developing treatments for this debilitating, lifelong disorder.

For more information, please visit: http://www.cidd.unc.edu/Angelman-Syndrome/.


Molecules and mechanisms for pain

Chronic pain is a major medical issue, affecting more Americans than heart disease, diabetes and cancer combined (American Pain Foundation). In our laboratory, we are developing new approaches to treat chronic pain. In addition, we study the neural circuits that transmit pain-producing stimuli using molecular, genetic, electrophysiological and behavioral approaches.