A photo of two people standing on either side of a poster showing research findings.
Joey Picone’s research involves identifying genes that impact drug tolerance in the brain. (Contributed photo)

Class of 2024: Joey Picone explores the neuroscience of addiction

Using gene-editing tools, the doctoral student uncovered new insights into how cocaine impacts the brain.

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Since childhood, Joey Picone has had an interest in science, especially biology and the natural world. 

“I have a lot of naturalist hobbies, like nature hikes and wildlife photography. My friends and I often go on trips to find and photograph rattlesnakes, pythons and other reptiles,” he said. 

Picone’s passion found a decidedly human shape in recent years: understanding the molecular mechanisms that impact our brain function. This month he graduates with a Ph.D. in anatomy and neurobiology from Virginia Commonwealth University’s School of Medicine.

By the time Picone began college, he knew he wanted to pursue a career in science. During his first week as a freshman at Christopher Newport University, he had the opportunity to talk with the director of CNU’s neuroscience program, who encouraged him to take the intro classes and talk to other faculty in the department. Before the week was over, Picone had connected with Olga Lipatova, Ph.D., to work in her research lab. 

For the next four years, he studied brain function related to learning and memory, which cemented his decision to continue his education in neuroscience. He applied to a variety of graduate programs but chose VCU, citing the university’s strength in research into the neuroscience of addiction. 

“Substances like drugs are able to hijack the learning and memory process in our brains, so studying addiction felt like a natural continuation of my undergraduate research,” Picone said. 

At VCU, he soon started working with Peter Hamilton, Ph.D., an assistant professor in the School of Medicine’s Department of Anatomy and Neurobiology who studies how experiences with stress and drug use change the brain.

“Dr. Hamilton was relatively new to VCU by the time I became a doctoral student,” Picone said. “At the beginning of my first semester, I got the chance to listen to him give a seminar about using gene-editing techniques to better understand the neuroscience behind addiction. I thought his research was so amazing, and we hit it off right away.”

As a doctoral student, Picone’s research involved identifying genes that impact drug tolerance in the brain. His work primarily focused on one gene called Zfp189, which has a role in the brain’s reward system. The genetic code that makes up Zfp189 is used to create a type of protein called a transcription factor, which controls how other genes are turned on and off in a cell.

“There are more well-known transcription factors associated with addiction, but many of these proteins have broad functions, so if you developed therapeutics to target these proteins, you could get unwanted side effects,” Picone said. “Instead, we wanted to target genes and proteins that are specific to drug use and addiction.” 

Picone used a gene-editing tool called CRISPR to gain insight into how this particular gene impacts the brain’s response to cocaine use. Using this technique, researchers can essentially alter the genetic code that makes up DNA to learn more about the proteins they encode, as well as change protein function.

Picone found that manipulating Zfp189 in mouse models impacted their physiological and behavioral response to cocaine. By editing this gene, he and his colleagues also discovered a way to inverse the function of the associated protein, which in turn inhibited drug tolerance in their experiments. 

“This research is so important since there are currently no FDA-approved pharmacotherapies for treating addiction to stimulants like cocaine,” Picone said. “Understanding the molecular mechanisms that drive this form of addiction is an important first step toward developing therapies for stimulant use disorder.” 

Reflecting on his time at VCU, Picone notes several highlights, such as publishing his first paper, earning an F31 grant from the National Institutes of Health and receiving the Charles C. Clayton Award from the School of Medicine. He credits Hamilton for helping him navigate academia and gain confidence as a researcher. 

“He taught me so much about how the academic field works, such as the ins and outs of putting together grant proposals and writing papers,” Picone said. “It was the perfect mentorship experience for me, and by the end, I felt incredibly independent.” 

Picone is now working as a postdoctoral researcher at the University of California, Irvine’s Department of Neurobiology and Behavior. As he reflects on his career path ahead, whether that be in academia, government or industry, Picone knows that he won’t get tired of doing his own experiments. 

“Even if I were to run my own lab, I know that I would always want to be hands-on in terms of performing my own research,” he said.