An interdisciplinary team of Carolina scientists is rewriting faulty instructions in genomes to treat genetic diseases without changing the DNA itself.
When you hear “DNA,” what normally comes to mind? If you’re like most, your brain fires up the image of the twisted, two-fold ladder we all remember from science class. What might not be as familiar as the double helix — but which proves to be at least as fascinating — is epigenetics, the study of hereditary changes that occur in our genome that do not involve changes to our genetic code.
The growing field of epigenetics holds the promise of future treatments for those facing cancer and rare diseases. Yet at the University of North Carolina at Chapel Hill, it’s not just the breakthrough potential of the field itself that’s exciting. It’s also how researchers from different departments are teaming up to push the science further and faster than they could do alone.
Brian Strahl, interim chair and professor of biochemistry and biophysics at the UNC School of Medicine, and Samantha Pattenden, associate professor at the Eshelman School of Pharmacy, are combining their expertise in chemical biology and epigenetics through a collaboration known as the Chemical Epigenomics Hub. Their common goal: identify, develop and apply chemical tools to better understand epigenetic processes, ultimately improving the treatment of human disease.
“The hub allows us to combine our multidisciplinary talents and strengths to do things that no one individual could do,” says Strahl. “At UNC, we are primed for collaborative endeavors, and the hub gives us the opportunity to come together and think about new areas of science.”
“The idea of convergent science, where we can have all these different fields coming together to be efficient with a project, is a great concept. It’s something we just naturally do here at UNC,” adds Pattenden.
Treating genetic diseases without changing the DNA
Strahl’s and Pattenden’s research is focused on the epigenome, which is an additional layer of genetic information that controls the “when and where” of how our genes are used. The epigenome controls DNA access, and when this system malfunctions, problems in the human body can arise.
“While epigenetics controls our normal development, we have also learned that its malfunction, just like a mutation of our DNA, can lead to disease,” says Strahl. “Excitingly, however, unlike mutations to the DNA sequence, changes in the epigenome are reversible. This plasticity makes the epigenome a fantastic target for therapeutic development.”
Histones — proteins that provide structural support to a chromosome — can mutate, leading to bone cancers or devastating pediatric brain cancers, which currently have limited treatments available. Strahl, Pattenden and the Chemical Epigenomics Hub team are focusing their work on these histones and the mutant forms called onco-histones that drive cancer. The hub will deliver a new understanding of how onco-histones contribute to the epigenome and will define new pathways and targets.
“About half of all cancers have mutations in the machinery involved with epigenetics,” says Strahl. “Through epigenetic chemical screens, we are working to identify new avenues or approaches that could lead us down a path toward identification of a pathway or particular drug that could be useful in treatment.”
“The advantage of epigenetics is that we don’t have to manipulate the genome,” adds Pattenden. “Epigenetics, unlike genetic mutations, are reversible. We can do things without actually changing the underlying DNA sequence.”
‘Team science is the best science’
Breakthroughs in epigenetics require teams with specialized skills, and the Chemical Epigenomics Hub brings necessary talents together from across campus. These include experts in epigenomics, model organisms, genomics, proteomics, chemistry and chemical biology.
The hub’s multidisciplinary foundation provides opportunities for Strahl and Pattenden to collaborate with researchers from the Center for Integrative Chemical Biology and Drug Discovery and more than 12 epigenetics laboratories, including labs from the medical and pharmacy schools, the Lineberger Comprehensive Cancer Center and the College of Arts & Sciences. And hub members don’t just hail from Chapel Hill. The team includes researchers from the Baylor College of Medicine and the University of Alabama as well.
“Different disciplines have different toolkits for addressing questions and problems in cellular and genomic research,” says J. Christopher Clemens, senior associate dean for research and innovation at the College of Arts & Sciences. “The amazing thing for me about this project has been watching how the team’s combined toolkit has worked in harmony to enlarge the scope of the questions that can be addressed. Just as you can improve carpentry with a hammer, a saw and a plane, team science can accomplish more than any one individual alone.”
Clemens, who is also the Jaroslav Folda Distinguished Professor of Physics and Astronomy, works to provide innovation frameworks that will help guide teams of researchers through the process of translating basic research into innovations with commercial or social impact.
The innovative work of the Chemical Epigenomics Hub kicked off with a 2019 award from the Creativity Hubs award program, which is managed by UNC-Chapel Hill’s Office of the Vice Chancellor for Research. The Creativity Hubs are virtual research networks that convene research talent and resources into diverse, interdisciplinary faculty teams that pursue answers to complex problems.
Strahl’s and Pattenden’s epigenetic hub is also receiving support from the Institute for Convergent Science, which is operating in a pilot phase in the Genome Sciences Building through a partnership between the College of Arts & Sciences, UNC Research, Innovate Carolina and other campus units. ICS provides wet lab and startup accelerator space, funding, talent connections and other resources designed to help faculty take a problem-centered, team-based approach to research that launches new treatments, products and devices into the world.
“Team science is the best science. It allows us to do projects we never thought possible,” says Pattenden. “Our team offers a one-of-a-kind constellation of strengths in epigenetics, model organism research, computational biology, medicinal chemistry and drug discovery.”
“The research we’re doing could potentially lead to new patents and approaches, but also lead to new science and new ideas,” says Strahl. “From a conceptual standpoint, we’re making new advances that could take us in directions we hadn’t yet realized would be important.”
A future epigenomics center
With the work of the Chemical Epigenomics Hub, Strahl and Pattenden hope to eventually create a world-renowned Chemical Epigenomics Center at Carolina that offers a synergistic environment where University faculty can come together to tackle the most challenging foundational and translational problems in the field.
“I’m hoping we see results that can take us into a new area, which ultimately could secure new grants,” says Strahl. “One of the main goals of the hub is that through our creativity and the work, we can standardize how we bring new grants to the table that weren’t there previously or wouldn’t have come otherwise.”
The future center would address challenges in epigenetics, expand the range of new drug targets and discovery efforts, spur new innovation and intellectual property and aid in the creation of new chemical tools. Such goals are ambitious, and Pattenden sees the hub’s collaborative approach to research and innovation as key to also making them attainable.
“Being at UNC has given me a new perspective on how to do science,” says Pattenden. “Team science doesn’t diminish an individual’s contributions. The things I could do would be so small if I wasn’t able to collaborate with people outside my own field.”
Chemical Epigenomics Hub Team
- Brian Strahl, principal investigator, UNC School of Medicine (biochemistry and biophysics)
- Samantha Pattenden, co-principal investigator, UNC Eshelman School of Pharmacy (Center for Integrative Chemical Biology and Drug Discovery)
- Ian Davis, M.D., UNC School of Medicine (genetics, pediatric hematology/oncology)
- Robert Duronio, UNC College of Arts & Sciengces (department of biology)
- Gregory Matera, UNC College of Arts & Sciences (department of biology)
- Daniel McKay, UNC College of Arts & Sciences (department of biology)
- Stephen Frye, UNC Eshelman School of Pharmacy (Center for Integrative Chemical Biology and Drug Discovery)
- Lindsey James, UNC Eshelman School of Pharmacy (Center for Integrative Chemical Biology and Drug Discovery)
- Dmitri Kireev, UNC Eshelman School of Pharmacy (Center for Integrative Chemical Biology and Drug Discovery)
- Ryan Miller, M.D., University of Alabama at Birmingham (pathology)
- John Sondek, UNC School of Medicine (pharmacology, biochemistry and biophysics)
- Nicolas Young, Baylor College of Medicine (molecular and cellular biology)