Dr. Elizabeth Heller
Dr. Elizabeth Heller’s early life was replete with hints of her future career. A self-described “nerd”, she assigned herself homework of her own creation and reminisces fondly on wandering through Rockefeller University’s campus with her father (a postdoc at the time). Liz’s early scholarly pursuits served her well; now, as an associate professor of pharmacology at the University of Pennsylvania School of Medicine, Liz studies mechanisms of gene regulation in the context of drug addiction and psychiatric disease.
Associate Professor University of Pennsylvania, School of Medicine
Postdoctoral Researcher Icahn School of Medicine at Mount Sinai
PhD Rockefeller University
Given Liz’s early passion for science, she began work in a microbiology lab as a high school student. She discovered she loved the lab environment and decided to pursue science in college, although she wasn’t sure which field of study she’d focus on. At the University of Pennsylvania, she took a freshman psychology seminar. When they reached a section on neurobiology, Liz was over the moon. Realizing she was more interested in the biology as opposed to the psychology of the brain, Liz decided to join a newly formed neuroscience specialization within the biology major. She also joined the lab of Dr. Ted Abel, where she worked at the intersection of behavior and molecular biology in sleep deprivation. Ted created an excellent lab environment, in which Liz learned the importance of strong, highly reproducible experiments.
As she was finishing her undergraduate education, Liz chose to apply to PhD programs to continue her neuroscience training. She vividly remembers her dad calling the landline in Ted's lab to tell her she'd been offered a place at Rockefeller. Ted’s response was “Great, then you know where you’re going!” Although Liz got into several other programs, Ted's strong praise for Rockefeller, its position at the forefront of the field, and its New York location made it an easy decision.
Once at Rockefeller, Liz rotated in the lab of Dr. Nathaniel Heintz. When discussing what her thesis work could be in his lab, he proposed that she could isolate synaptic populations from glutamatergic cells at each of the five different cortical layers and profile them proteomically. The specificity of the question and novelty of the methods and tools appealed to Liz, who told Nathaniel that “it was the only project she wanted to work on.” However, isolating synapses from these cells proved technically challenging. She generated transgenic mice in which each mouse line (one for each cortical layer) was supposed to express an AMPA receptor fused to GFP in one of the cortical layers’ glutamatergic neurons. However, these AMPA receptors were not being trafficked to the synapse in any of the mouse lines. Liz had also generated a control transgenic mouse with a GFP-tagged inhibitory receptor subunit, and this fusion did traffic to the synapse. She switched to characterizing inhibitory synapses and found that the inhibitory synapses primarily expressed structural proteins but not signaling molecules.
When it came time to look for a postdoc, Liz hoped to continue her focus on inhibitory synapses, and to stay in New York where her community was. A postdoc in the lab suggested she look into the lab of Dr. Eric Nestler, who was moving from Texas to New York. Liz looked through his papers and saw that his lab’s emphasis on molecular biology and behavior matched her interests perfectly. Fittingly, Eric had recently started to focus on methylation and epigenetic regulation in the brain, which requires making many genetic constructs. Liz’s PhD work developing several transgenic mouse lines meant she had a lot of experience working with genetic constructs, making her a great fit for this direction in Eric’s lab. The project focused on the epigenome and its effect on gene regulation in the context of drug addiction. Liz selectively induced epigenetic remodeling at the Fosb locus in the nucleus accumbens and found that this was able to change a mouse’s response to cocaine, demonstrating a link between the epigenetic state of a gene and a behavioral phenotype. Liz was the first to apply epigenome editing in the brain in vivo.
While in her postdoc, Liz read a paper that suggested that these epigenetic markers might change not only gene expression but splicing as well. This was a novel idea; the field of epigenetics and the field of RNA had largely been separate up until this point. Liz wanted to study the intersection between the epigenome and splicing and decided to apply to faculty positions with this idea in mind. She got offers from two universities and settled on UPenn, her alma mater. Her lab still studies chromatin-regulated alternative splicing, but has branched out as well, generally studying the epigenetic remodeling that occurs in drug addiction and psychiatric disease.
Liz uses the lessons she has learned from her advisors as well as her experiences in science to inform how she mentors her students, placing a strong emphasis on the training aspect of her job. She describes designing projects which play to a student’s strengths and which allows them to thrive early so that they develop confidence in their abilities. She also describes the deliberate steps she takes to engender respect and collegiality in the lab, such as concluding meetings by checking in on her trainees, hoping that they feel valued and cared for. The enthusiasm, sincerity, and intentionality with which Liz approaches both her science and her mentoring are clear hallmarks of her story, and there is no question that these features will continue to shape both the field of epigenetic neuroscience and the trajectories of her own trainees.
Find out more about Liz and her lab’s research here.
Listen to Rianne’s full interview with Liz on August 8th, 2023 below!
