MY EXCELLENT ADVENTURE:
FROM BEHAVIORAL PHARMACOLOGY TO EPIGENETICS
(BY CHRIS PIERCE, CO-STARRING COCAINE)
KENTUCKY
OR: How did a Kentucky kid one generation removed from dirt poor tobacco farmers make it good in addiction neuroscience?
(That's the actually tobacco farm where I grew up - the inset is an artists' rendition of me as a young man).
Born in Somerset, Kentucky; Raised in Frankfort, Kentucky
Graduated from Western Hills High School
(that's me on the left in both pictures)
College at the University of Kentucky
I was incredibly fortunate to work in Mike Bardo's lab for three years
The Bardo Lab is where the research bug bit, leading to an obsession with the role of dopamine in motivated behaviors.
Mike and I published seven papers together including my first first-author paper.
INDIANA
Graduate school at Indiana University,
starting in Fall 1989
Learned voltammetry and behavior in George Rebec's lab (that's him on the left. Mark Wightman was across campus in Chemistry).
PhD defense
October, 1993
What I learned in graduate school
(reduced to four bullet points)
• Addiction is a form of neuronal plasticity.
• The plasticity relevant to addiction takes place in the
limbic system.
• Glutamate plays a critical role in neuronal and behavioral
plasticity.
• I need to study the role of glutamate in addiction and
Peter Kalivas’ lab is the place to do it.
So I loaded up the truck, and moved to Pullman, Washington.
(October, 1993)
WASHINGTON STATE
Peter was and is a fantastic mentor.
We had a great working relationship, when he wasn't trying to kill me...
Not kidding. This photo is from my interview. White water rafting on the Salmon River in Idaho. Also known as "the river of no return". Not making that up.
Peter was an expert in microdialysis/HPLC, then an emerging technology.
We published one of the first papers examing the role of glutamate in behavioral sensitization to cocaine.
This manuscript has now been cited over 500 times.
We also published a paper on CaM-KII and cocaine-induced neuronal and behavioral plasticity, a topic I would return to when I started my first lab at Boston University School of Medicine.
BOSTON
I was incredibly forunate to work with a series of outstanding graduate students at Boston University.
Including Stephanie Licata, Ghazaleh Sadri-Vakili, Sharon Anderson, Heath Schmidt and Ausaf Bari, some of my closest friends to this day.
Most people studying animal models of addiction adopted the intravenous self-administration (IVSA) model in the 1990s. We were no exception. The IVSA/extinction/reinstatement model of craving in particular became the standard in the field.
We showed that the mPFC to accumbens glutamatergic pathway played a critical role in the reinstatement of cocaine seeking. (Similar to work emerging from the Kalivas Lab - remind me to never try to compete with Peter again)
Our paper (Park et al., 20002) has been cited over 250 times.
The circuitry underlying the reinstatement of cocaine seeking was coming into focus. Incredibly interesting, but how would that translate into therapeutics? The lab suggested that we try deep brain stimulation (DBS) in our craving model. My response: "They'll never use DBS for psychiatric disorders clinically so what's the point?". Within months, the famous Mayberg paper appeared...
Fair Vassoler, then a technician in the lab, undertook our first DBS study. We collaborated with Conan Kornetsky's lab, using their ICSS equipment to administed the DBS. This was one of our last papers from BU. We've studying DBS in craving models ever since (9 papers total, 2 in 2023).
I worked with many terrific faculty members at BU, who provided invauable advice as I transitioned into independence.
My BU Pharmacology faculty farewell dinner. Conan Kornetsky, Susan Leeman, Bryan Yamamoto, Carol Walsh, Ben Wolozin, me, Terry Gibbs.
2008
2008: Not a good year for a lot of people
2008: A great year for me
We published a paper that was a culmination of all the concepts of cocaine craving that we had developed to that point (dopamine, glutamate, AMPA receptors, CaMKII, all of it).
I received the Waletsky Memorial Award for addiction research from the Society for Neuroscience (honoring Jacob Waletsky).
I joined the faculty of the University of Pennsylvania School of Medicine Center for Neurobiology and Behavior.
2008 was quite a year!
My last summer in Boston, I met with former student Ghazaleh Sadri-Vakili and her postdoc mentor Jang-Ho Cha. That discussion led to a collaboration focused on epigenetic effects of cocaine.
Stephanie Licata, Ghazaleh Sadri-Vakili and me.
In that meeting I learned that epigenetics is defined as a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence. And the epigenetics folks take that word heritable very seriously. More on that later.
PHILADELPHIA
Scenes from the move into TRL
Fair Vassoler, a graduate student at BU, moved with me to Penn. I convinced Heath Schmidt, a former PhD student at BU, to leave Yale and join us at Penn as lab manager. Fair is now on the faculty at Tufts. Heath holds a named professorship at Penn. A pretty great team to start a new lab!
Charles P. O'Brien at the unveiling of his portrait ceremony.
A nice photo of Chuck, but I wish I had one of us skiing together at Winter Brain.
Below is a picture of his most amazing office.
I will be forever grateful to Chuck O'Brien, who advocated for Penn to hire me. In October, 2008, I moved into the lab space recently vacated by Gary Aston-Jones. Gary left to join Peter Kalivas' department at MUSC. Gary will turn up again in this story.
When I got to Penn, I asked Chuck what I could do for him. He didn't hesitate: Penn used to have a NIDA T32 and we needed a new one to support our training activities. Chuck suggested that Anna Rose Childress and I work on it together. Less than two years later (in 2010) NIDA funded our Translational Addiction Research Program supporting four predoctoral and four postdoctoral fellows. Anna Rose and I shepherded this T32 through two renewals. It's still going strong!
We organized a named lecture in Chuck's honor. He once told me that this was the honor of which he was most proud. That's a little hard to believe considering he was knighted in France, but it was a nice sentiment. Speakers over the years included many of Chuck's favorites: Yavin Shaham, Markus Heilig, Peter Kalivas, Marina Picciotto, Elliot Stein and Jon-Kar Zubieta.
My friends at Temple recruited me into leadership of the Philadelphia Society for Neuuroscience. When I agreed, they then let me know that I was organizing the next meeting! Similarly, we elected Mat Wimmer to take over as President when he left a dinner to take a phone call! Many fond memories of Philly SfN meetings and outreach activities.
I worked with an amazing group of people at Penn including Heath Schmidt, Fair Vassoler, Lisa Briand, Pavel Ortinski, Leonardo Guercio, Mathieu Wimmer, Samantha White, Bruno Fant, Mack Hofmann, Sarah Swinford-Jackson and Matthew Rich.
Remember that discussion about transgenerational epigenetics we had back in Boston? Fair Vassoler wanted to give it a try. I urged her not to, arguing that it probably wouldn't work and would take an enormous amount of time and effort, thus delaying her thesis (which focused on the mechanisms of DBS). She didn't listen; she was right.
Perhaps not surprisingly, this paper got a lot of attention in the popular press including a piece on the Colbert Report.
www.cc.com/video/s2213y/the-colbert-report-tip-wag-hopped-up-pops-starbucks-american-consumers
NEW JERSEY
In 2014, Gary Aston-Jones left MUSC to become the inaugural Director of the Brain Health Institute at Rutgers University.
Bet you can guess where this story is heading.
On the road again!
11 years in Boston.
11 years in Philadelphia.
It was a good run at Penn, but as of 2019 I was ready for a change. When Gary called, I was primed to make the jump from the urban landscape of cheesesteaks and Questlove to the Jersey suburbs, home of fat sandwiches (served from grease trucks) and Springsteen.
Sarah and Matt moved from Penn to Rutgers. Couldn't have done it without them.
My beloved orchids love the new office!
March 2020
We started our first experiment at Rutgers.
Morgan James took Andrea and I to a Rutgers basketball game.
Then, the world stopped.
The lab was closed for over three months.
Thanks to the dedicated efforts of Sarah, Matt, Sharvari and Samantha we managed to maintain productivity during this difficult period.
In 2020, Paul, Ellen and I edited the second edition of Addiction for Cold Spring Harbor Press.
At Rutgers, we have continued our work on mechanisms underlying deep brain stimualtion and transgenerational effects of paternal cocaine.
