Korb Lab Investigates Epigenetic Regulation in Autism – A PostDoc Interview
Written by Audrey Goldfarb, Ph.D. – ASPE Postdoc
The Epigenetics of Autism
What makes certain genes behave differently in the brains of people with autism?
That question drives the work of Dr. Erica Korb, an ASPE investigator with an upcoming publication in Genome Research on the neuroepigenetics of autism. Epigenetics—literally meaning “upon genetics”—examines how chemical modifications to DNA and its packaging into chromatin influence gene activity. Changes in these epigenetic mechanisms can turn genes on or off without changing the underlying DNA sequence.
In the brain, genes that regulate epigenetic processes are critical for proper neuronal function, and their disruption has been linked to autism. Korb’s research group focuses on genes implicated in autism that encode transcriptional regulators—proteins that control when and how genes are expressed. To tackle this question, she collaborated closely with two researchers in her lab, Dr. Alekh Paranjapye and Rili Ahmad. “Our goal,” Korb explained, “was to take a broad look at the mechanisms that regulate transcription and are also connected to [autism].”
Dr. Alekh Paranjapye and Rili Ahmad combined their expertise to execute the study. “I think regulators are especially neat to study because their roles are so broad, which reflects the broadness of something like [autism],” Paranjapye said. “Rili and I wanted to do a more intensive analysis, including more targets and stronger, larger-scale methodologies, to really drill into shared targets and pathways.”
“This is a great example of how we can bring together expertise in the lab to be able to move really effectively and quickly to tackle quite a large number of genes,” Korb said. “This was really an impressive effort to tackle a massive data set and learn a huge amount from it.”
All Roads Lead to Chromatin
After selecting key autism risk genes involved in transcriptional regulation, the team set out to uncover how these genes affect downstream targets. They chose nine distinct autism risk genes encoding transcriptional regulators, and found that depletion of any of these nine genes disrupted a common set of downstream genes. “[These downstream genes] often have unique chromatin features, which can include things like bivalent domains or specific enhancer signals that are sort of embedded within the chromatin,” Korb said. (Bivalent domains are regions of DNA poised to either activate or silence genes, depending on developmental cues.) “I think these domains are understudied, and they present a mechanism that could explain why certain genes are so sensitive in neurons.”
Having uncovered molecular disruptions, the team next asked how these transcriptional changes might translate into differences in neuronal activity. Chromatin structure helps regulate gene expression throughout development, and disruptions to chromatin often underlie neurodevelopmental disorders like autism. “Our data suggest that at this particular time point in neuronal development, these genes are highly sensitive to disruptions to transcription,” Korb said. “And these synaptic genes and proteins that play functional roles might underlie some [autism] phenotypes.”
MEA: Watching Neurons Fire Away
To understand how these transcriptional changes translate into neuronal function, the team turned to electrophysiological analysis. Korb, Paranjapye, and Ahmad performed a technique called multielectrode array recording, or MEA, which allowed them to monitor the electrical activity of live neurons. “This is an experiment we can do on live cells and record at multiple time points as neurons are maturing and forming networks,” Korb said. “It’s a really powerful approach that gives us the ability to do longitudinal analysis.”
They found that depletion of any of these autism-related genes caused defects in neuronal firing patterns. “That tells us that these autism genes, despite having different direct effects on transcription and chromatin, can disrupt similar sets of genes and ultimately have similar functional effects on neuronal output,” Korb said. In other words, the same genetic disruptions that alter chromatin structure also change how neurons “talk” to each other.
Incorporating Environmental Risk Factors
While genetic factors account for most autism susceptibility, understanding how environmental exposures interact with those genes could reveal new insights into autism. “Autism Spectrum Disorder is predominantly genetic, with most estimates putting it around 80% of genetic risk contributing to the disorder,” Korb said. “But there are certainly some environmental factors that can contribute. We ultimately also want to layer on some of these environmental factors and see how they interact with the underlying genetic factors.”
The Korb lab is currently modelling these gene-environment interactions in cell and mouse models, focusing on endocrine-disrupting chemicals (EDCs) that people are exposed to regularly. Paranjapye, who is leading the project, aims to detect how these EDCs may exacerbate autism phenotypes when combined with genetic factors. “I found some pretty striking interactions,” Paranjapye said.
As their research expands from genes to the environment, the Korb Lab is piecing together a more holistic view of autism—one that reflects the complexity of biology and lived experience alike.
Spreading Safe Science
As the Korb Lab continues to uncover these complex interactions, they also recognize the importance of communicating accurate, evidence-based information about autism to the broader public.
Like many scientists, Korb often finds herself in the position of providing science-backed information to family and friends who are inundated with news headlines and mixed information. For Korb and others, the ASPE community has provided exceptional support and resources for staying up to date on our current understanding of autism diagnosis, susceptibility factors, and recommendations. “We’re able to learn firsthand about new science and susceptibility factors that are identified in ASPE families,” Korb said. “This puts us in the unique position of being able to study emerging factors that have a real basis in scientific evidence.”
Korb advises fellow scientists to take a compassionate approach when dispelling false information and explaining data. “When we’re flooded with misinformation, it can be really scary for people to try to parse what they’re hearing,” Korb said.
By pairing rigorous research with empathy and clarity, the ASPE community is helping bridge the gap between discovery and public understanding of autism—reminding us that advancing autism science is as much about communication as it is about genes and neurons.
Read the full paper here!
Up next: a jargon-free recap of this interview, made for every curious mind.
This interview was written by Audrey Goldfarb, Ph.D., (ASPE PostDoc in the Korb lab). Audrey received her B.A. in Biology from the University of Rochester in 2019, where she studied cancer avoidance mechanisms of long-lived rodents in the labs of Vera Gorbunova and Sina Ghaemmaghami. She completed her Ph.D. in the de Lange lab at Rockefeller University in 2025, where she studied mechanisms of telomere protection by the shelterin complex. In the Korb lab, Audrey is primarily interested in the epigenetic mechanisms underlying neurodevelopmental disorders. Outside of the lab, Audrey enjoys science communication, fiction writing, cycling, yoga, and being in nature.