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Faculty Spotlight: Audrey Dickey, PhD

Tuesday, November 14, 2017
Dickey

Audrey Dickey, PhD, first took on the role of a mentor with her little brother, then moved on to teaching others everything from how to play a xylophone to how polymerase chain reactions work. Now, as one of our newest research faculty, she’ll be establishing preclinical trial programs for Parkinson’s and Huntington’s disease while continuing to mentor undergraduate and graduate students. In this Faculty Spotlight interview, Dickey talks to us about her new role at Duke, how she moved from studying chimps and killer whales to neuroscience, and what she enjoys most about being a mentor.

What are your current responsibilities within the Neurology Department? What are your top priorities for the next several months?
As part of the newly established Center for Neurodegeneration and Neurotherapeutics, my focus is on rebuilding the translational preclinical trial program that I established at the University of California - San Diego for studying neurodegenerative disorders including Parkinson’s and Huntington’s diseases. My team has just finished what appears to be a successful pre-clinical trial with a Parkinson’s disease model, but we have some mechanism experiments to wrap up prior to submission.

How did you first get interested in neuroscience? What do you enjoy most about the field?
My Canadian doppelgänger intervened! I was working with chimpanzees and killer whales, which was fascinating, but seeing the research of “my alternate self” inspired me to move towards molecular & cellular neuroscience with an eye towards translational aspects.

I enjoy mentoring and seeing the excitement when someone is successful or the flash of understanding of a concept. My mentees are motivated by knowing that their efforts could beneficially affect the life of someone else. It is important to not only share our research with patents, but to hear their perspectives, and their priority issues. I also really enjoy the feedback and collaboration with other scientists, when you’ve just given a talk and people come up and ask, “did you think about this?” Or “what if you tried that?”

How did you first get started as a mentor? What do you enjoy most about this role?
I guess having a little brother gave me a head start on how to demonstrate and explain things, which happened with schoolmates up through grad school. Explaining how to play a xylophone or calculus or PCR – I worked with the person who was learning to explain it in their terms. When I started as a post-doc straight out of grad school, I was immediately assigned a graduate student to mentor, and then I had one undergrad interested in working in a lab… and another, and another, and then another grad student, etc. I’m so proud of what they’ve learned and their successes. (It was inside them all along!)

You earned your PhD in neuroscience. What topic did you study for your dissertation? How does what you learned during this study affect your current work?

For my doctorate I examined the effects of a kinase/phosphatase duo on the form and function of mitochondria, and how the effects on mitochondria affect synaptic formation and plasticity and thus learning and memory.

I noted that the morphology of mitochondria and their localization in the dendrites of primary hippocampal neuron cultures affect dendrite outgrowth and synapse formation via the effect of the mitochondria metabolism on ATP production and calcium buffering. Considering my initial findings, I hypothesized that mice with altered neuronal mitochondria would also have affected dendrite outgrowth and synapse formation, which would lead to alterations in Long-Term Potentiation (LTP), and thus learning and memory. Indeed, when I characterized mice with altered neuronal mitochondria, they displayed issues with multiple learning and memory assays including the Barnes maze, fear conditioning, and novel object recognition.

Protecting neuron from death by drastically modifying mitochondria function unfortunately also interrupted cognition and learning in mice. This indicates caution when applying certain approaches to therapeutic interventions in stroke and brain disease as they could potentially interfere with normal cognitive functioning and memory.

This led me to be interested into how to preserve neurons in disease without ruining their ability to act as neurons (or another adverse side effect).

You were the lead author of a recent study that identified PPARd, a protein normally found in the body but repressed in people with Huntington’s disease. What were the main findings of that study? What implications does that study have for possible therapies for Huntington’s disease?
PPARd is a transcription factor induced by exercise, and it affects multiple cellular functions, including regulation of mitochondria. My team determined that poly-Q-expanded huntingtin directly interacts with PPARd, a transcription factor co-activated by PGC1a. This effect of repression by huntingtin on PPARd can be recapitulated by a single-point mutation of PPARd in mice which develop over time many symptoms similar to Huntington’s Disease, including mitochondrial dysfunction.

We were fortunate in that when we were in search of a PPARd agonist with little or no side effects, our collaborators at Sanford-Burnham-Prebys saw my preliminary data and reached out with KD3010, which had already been tested in two clinical trials with good metrics in the toxicology testing. After KD3010 successfully passed through our in vitro battery of tests, my team tested this compound in a rigorous preclinical trial carried out according to NIH-guidelines.

Every experiment can give us a new piece of the puzzle of Huntington’s Disease. Therapy directed towards PPARd can have beneficial effects on mitochondrial dysfunction, aggregation, and inflammation among others. This is not the final answer, but with each experiment, scientists around the world are refining the puzzle pieces that make up this disease, and what can be part of the solution.

Dickey
Dickey poses with students she mentored while at the University of California - San Diego.

What passions or hobbies do you have outside of the Department?
I love traveling, sci-fi, superheroes, and games with friends. Some of my favorites are Doctor Who (classic and new), Firefly and Serenity, Sherlock, Rogue (X-men graphic novel version), and Superman. I also love to travel. love to travel.  The favorite places I've been to so far were in Italy: Florence where there are so many gorgeous sights to see, and the huge temples at Paestrum. I’ve always been intrigued by ancient Egypt, so one of these years, I’d love to travel and see the variety of pyramids and temples there.