Elizabeth Heller’s lab uncovers how drug addiction can create lasting changes in genes

When Elizabeth A. Heller, PhD, says she researches drug addiction, people may have misconceptions about her area of expertise. “People may think addiction research is only about behavior,” said Heller, an assistant professor of Pharmacology and the head of a laboratory of Neuroepigenetics.

Instead, Heller’s work and the work of her 10-person lab is focused on molecular brain mechanisms, aiming to uncover chronic changes that can happen and keep happening in the brain long after exposure to addictive substances like cocaine ends.

Heller’s dedication to basic science is matched only by her commitment to colleagues, her students, and those who may one day benefit from the breakthroughs made in her lab. Below, she speaks about uncovering a love of neurology, her unique research, and running a neuroscience lab throughout the pandemic.

Briefly describe your background and how you came to Penn.

I studied at the University of Pennsylvania for undergrad in the early 2000s before going to Rockefeller University for a PhD in Molecular Biology. I was drawn back to Penn because, not only was it my alma mater, but it was the home of innovative and thought-provoking neuroscience and epigenetics research and the principal scientists leading discovery in the field. It was a place that fostered my love of investigation.

There were people on faculty like one of my mentors, Ted Abel, PhD, a former professor of Biology at Penn and now chair of Neuroscience at the University of Iowa, with whom I was lucky enough to work during my undergraduate studies (we looked at sleep deprivation and memory in mice.) Having experience doing research and being part of a lab as an undergraduate was foundational for me, and kudos are due to Penn and my mentors for offering that experience. I was confident that Penn would allow me to pursue breakthroughs with some of the brightest experts. I returned here in 2009 and have continued my professional journey here ever since.

What research are you currently undertaking?

My work is divided into a few various topics, but it’s all within neuroepingentics. Genes, which we inherit from our parents and their parents, aren’t locked like we used to believe. They’re susceptible to change from environmental effects. Those effects can cause activation or repression of certain parts of the code. Sometimes changes are very small, like a change to one note in a piece of music. Neuroepigenetics deals with those environmentally caused gene expression changes within the brain.

Specifically, much of our research at my lab revolves around the role of chromatin—a complex of DNA and proteins within the nucleus of a cell—in neuroepigenetics and the effects of cocaine. It’s a drug that’s only chemically addictive in a minority of users. But within those who become addicted, the likelihood that someone fully quits goes up if they can refrain from use for a year. That made me and my colleagues think that something happens in the brain at late abstinence that may help patients recover.

After multiple studies in mice, we found that although cocaine dissipates in the body fairly quickly, changes within the brain keep happening long after use has stopped. It triggers a chronic reaction. The hope is that, if we can identify the mechanisms behind the ongoing changes before the brain enters recovery, then pharmacologists and scientists could potentially develop a treatment to either trigger brain recovery sooner or halt ongoing changes to the brain.

What inspired you to do the research you’re doing?

I was sincerely inspired by all the early experiences I had in the lab, like those I had as an undergraduate student at Penn, and the researchers who gave me an opportunity to question and explore. I feel I owe that same support to the young scientists I work with today.

Additionally, those who have substance use disorder continue to be stigmatized. Drugs affect people in various ways. And while it’s clear that drugs like cocaine are harmful, that fact should not keep scientists from researching the scientific mechanisms behind it. Greater understanding on a basic-science level may someday lead to greater numbers of people overcoming addiction and could lead to treatments for a myriad of other neurologic conditions. The promise of science and the potential it has to benefit humanity continues to inspire me.

What are the biggest challenges you face as a scientist?

The pandemic. During the pandemic, I had a newborn and a young child. I was managing motherhood and running a lab, trying to advance science and compete for funds to support the lab and all those whose livelihoods depend on it. Thankfully, Penn’s support also helped us through the challenging pandemic era.

It’s funny. I was the working woman you hear on the news whose life is “terrible,” balancing work and home life, and who should be incredibly stressed. It was difficult, and I was stressed. But caring for young children who had no idea what was going on was actually really rejuvenating. There was just joy from these little humans who were completely separate from the outside world.

I am also an adult who has built up resilience from simply living life. That’s not the case for some of our young students and researchers. I feel most for those in our lab and in my classes who haven’t had the life experiences to cope with the stress the pandemic brought. Some are burned out, and it seems that they are just beginning to process everything. Department leaders, professors, and mentors owe it to this next generation of researchers to do what we can to listen to them and try to offer them the support that can help them move forward. I think we’re just starting to have those conversations, but they’re important.