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Audrey Brumback, MD, PhD

Profile written by E. Steve Roach, MD

Audrey Brumback, MD, PhD

This year’s Phillip R. Dodge Young Investigator Award recipient is Audrey Brumback, MD, PhD of the University of Texas Dell Medical School in Austin, Texas. The award will support her continuing effort to define the mechanisms of corticothalamic circuit dysfunction in autism. Long-term, she envisions that these studies could lead to novel circuit-based treatments for individuals with autism.

As a National Merit Scholar, Dr. Brumback studied biochemistry at the University of Texas at Austin, graduating with honors in 1999. She then entered the University of Colorado’s Medical Scientist Training Program, earning a PhD in neuroscience in 2006 and an MD two years later. She successfully defended her thesis “Thermodynamic regulation of NKCC1-mediated chloride cotransport underlies plasticity of GABAA signaling in neonatal neurons.” Her thesis advisor was child neurologist Kevin Staley. Dr. Brumback next completed a one-year internship in pediatrics at the University of California San Francisco, then entered pediatric neurology residency via the neuroscience pathway. For a year she served as Chief Resident of Child Neurology at UCSF, and finished the residency in 2013.

Dr. Brumback credits her current research path to a mixture of serendipity and mentorship. She finished residency intent on continuing her research career as a post-doctoral fellow. One of her faculty mentors suggested that she work with Vikaas Sohal, a psychiatry- trained physician-scientist who studies how the prefrontal cortex influences disorders such as autism and schizophrenia. Sohal was working with a still new technique called optogenetics, which seemed like a natural fit with the patch- clamp techniques she had utilized during her PhD studies. Optogenetics involves the insertion of genes into neurons followed by the use of light to activate or inactivate the modified cells. The optogenetic technique allows levels of sensitivity and specificity that are not possible with standard electrical brain stimulation.

Autism was an attractive area for study. It is common, but its pathophysiology is poorly understood. Several animal models of autism already exist. Although the brain is structurally normal in most individuals with autism, clearly there is neuronal dysfunction to be identified if one has a sensitive enough analytic tool. A number of genes have been implicated in autism, but how these genes trigger the clinical manifestations of autism is not understood. Thus began her study of convergent mechanisms of prefrontal cortical dysfunction in mouse models of autism at the UCSF Center for Integrative Neuroscience.

With characteristic diligence, Dr. Brumback set about becoming proficient at the new optogenetic technique, understanding the earlier studies related to autism, and mastering the clinical features of autism. She attended an autism “boot camp” at Cold Spring Harbor, started to seek out children with autism in clinic, and began working with her department’s clinical experts. Using whole cell patch clamp electrophysiology, she documented deficient excitability of prefrontal corticothalamic neurons in three mouse models of autism (fragile X knockout, CNTNAP2 knockout, and prenatal valproate exposure). She then performed in vivo calcium imaging in awake, behaving mice and observed that these abnormal corticothalamic neurons do not activate appropriately during social interactions in autism model mice. Then, using in vivo optogenetic stimulation in awake, behaving mice, she observed that the social behavior of the model mice can be bi-directionally altered by optogenetic activation or inactivation of these abnormal prefrontal corticothalamic neurons. These studies laid the groundwork for the work to be supported by the Dodge Award – the use of mouse models to examine how the prefrontal corticothalamic circuit participates in autism- associated behaviors.

As the daughter of a child neurologist, one might think that Dr. Brumback’s decision to enter the field would have been direct. But when asked why she chose to specialize in child neurology, she replied, “Well, I tried to play hard to get with neurology. With each clinical rotation, I tried to imagine myself as a practitioner in that field, but my mind always veered back to the brain. For OB/GYN, it was how does the fetal brain develop? For ophthalmology, it was how the retina is a window to the brain. I did my neurology clerkship at the end of the year, and after the first half day of clinic, it was obvious this was where I belonged.” Later, during the first day in pediatric clinic, she thought, “I’m a pediatric neurologist. Done.”

In addition to her success as a researcher and clinician, Dr. Brumback and her husband MacKenzie Howard have two adorable preschool daughters. Since 2012, she has also spent one week per year in Mexico as a volunteer for the Rotary Club’s Proyecto Niño annual medical service mission. How does she manage it all? “Well, first, I have an equal partner in my husband,” she explains. “And as researchers, we both have flexible schedules, which is such a gift.” One suspects that balancing her work and family life also has something to do with dedication, organization, and plain hard work.

Dr. Brumback has already made substantive scientific contributions, but she has also mastered an array of research techniques that should ensure continued contributions. Equally important, she combines a passion for research with a deep-seated desire to help the individuals with autism. We could not have selected a more appropriate winner of the Phillip R. Dodge Young Investigator Award.