NIH Awards Aim To Unwrap the Unexpected Molecular Links Between Breast Cancer and Childhood Brain Disorders
Two major NIH grants will support Lluis Morey, Ph.D., as he investigates how Polycomb proteins drive breast cancer growth and contribute to mutations that disrupt brain development.
As a kid, Lluis Morey, Ph.D., an associate professor in The Dr. John T. Macdonald Foundation Department of Human Genetics at the University of Miami Miller School of Medicine, wanted to be a doctor. But when he asked his physician father if he always understood the underlying reasons his patients got sick, the answer was no. That type of study, his father explained, was the work of biochemists and molecular biologists.
Dr. Morey decided then, at around 15 years old, that his goal in life was to run a lab focused on uncovering the mechanisms that drive human disease.
Today, Dr. Morey is a cancer epigenetics researcher at Sylvester Comprehensive Cancer Center, part of the Miller School. His lab runs two parallel research programs, one on breast cancer, one on neurodevelopmental disorders, connected by the actions of essential proteins that make up Polycomb complexes.
“Polycomb complexes were discovered in the ’50s, and it’s only in the last 15 years that we’ve begun to fully understand their canonical role during normal development,” said Dr. Morey. “We’ve been uncovering non-canonical actions of these proteins in disease, but to understand those roles is going to take us 20 more years.”
One Mutation to Derail the Brain
Every cell in the body contains the same DNA. During development, some become brain cells and others become breast cells. Polycomb complexes are a big reason why. They regulate the decisions that cells make during early development that determine their fate.
Early studies found that, when flies lack Polycomb activity, they grow legs where their eyes should be. That striking discovery pointed to Polycomb proteins’ function to funnel cells toward their final identity by silencing genes that belong to other cell types. They also help adult tissues repair and renew themselves.
To drive those changes, Polycomb proteins regulate gene expression without changing the genetic code itself, a process called epigenetics. They do this primarily by chemically modifying histones, the proteins that DNA wraps around. But the machinery is far more complex than it first appeared. Dr. Morey’s early research, published in Cell Stem Cell in 2012 and 2015, found that there are more than 100 distinct Polycomb complexes, each set of proteins playing unique roles.
New Genetic Mutations Linked to Neurodevelopmental Disorders
Because Polycomb proteins are essential during development, Dr. Morey wondered about their role in neurodevelopmental disorders. This broad category includes intellectual disabilities, autism spectrum disorder and anxiety disorders that affect roughly one in six children in the United States.
Working with genetic testing partners, including the Brazilian firm Mendelics, Dr. Morey’s lab published a paper in February 2026 in Molecular Cell that linked several novel Polycomb gene mutations to intellectual disabilities.
They also created the first preclinical model of a Polycomb mutation linked to neurodevelopmental disorders. The model showed that the mutation disrupted the formation of new brain cells, reduced sociability and increased anxiety.
“It’s incredible that one single nucleotide change can derail development and lead to anxiety and autism,” said Dr. Morey.
The new NIH R01 will fund additional preclinical models to study how these Polycomb mutations affect the brain and behavior.
“We can’t reverse how the brain is wired,” said Dr. Morey. “But if we understand the mechanism, we may be able to develop compounds that alleviate those symptoms. That’s what we’re working toward.”
A Molecular Gatekeeper Gone Rogue
The other side of the lab is studying what happens when these essential molecules go rogue. In a study published in 2018 in Nature Communications, Dr. Morey’s team found that P complexes behave very differently in breast cancer. Rather than silencing genes, they switch to activating pathways that fuel tumor growth. What causes that flip remains an open question.
“For 80 years, Polycomb was known only as a gene repressor,” said Dr. Morey. “In this research, we showed that it can do the opposite in cancer. Now we’re hoping to better understand why and how it happens, and find ways to stop it.”
Dr. Morey received a new NIH R35 grant to support that work. He suspects the switch involves Polycomb acting on proteins other than histones in cancer cells, a mechanism that has never been explored.
His research also suggests Polycomb may be involved in another major driver of breast cancer, hormone resistance. The most common breast cancer subtype is estrogen receptor-positive. Hormone therapy is an effective treatment for these cancers, but many patients stop responding to the drugs over time.
A 2020 paper in Science Advances from his lab linked hormone therapy resistance to changes in Polycomb’s regulation of the estrogen pathway. Another paper, published in April 2026 in Genes & Development, uncovered a new role for Polycomb complexes in the three-dimensional organization of DNA in the nucleus of breast cancer cells. Furthering this work is another focus of the R35 grant.
Two Diseases, One Target
At first glance, breast cancer and neurodevelopmental disorders have little in common. But for Dr. Morey, both are windows into the same fundamental question, the one his father couldn’t answer when he was 15. What makes people get sick?
“Our goal is to understand the molecular basis of these diseases. Once we understand the mechanism, we have a target,” said Dr. Morey. “We can then work on treatments to help alleviate symptoms of neurodevelopmental disorders, which might one day be useful in breast cancer, too.”
For Dr. Morey, having the support of Stephen D. Nimer, M.D., director of Sylvester, professor of medicine, biochemistry and molecular biology, executive dean for research and the Oscar de La Renta Endowed Chair in Cancer Research at the Miller School. That willingness to embrace new research avenues has made both programs possible.
“Dr. Nimer believed in me,” he said, “and I really appreciate it.”
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Tags: anxiety, brain health, breast cancer, cancer research, Cognitive impairment, Dr. John T. Macdonald Foundation Department of Human Genetics, Dr. Lluis Morey, epigenetics, estrogen receptor positive breast cancer., gene editing, genetics, Sylvester Comprehensive Cancer Center