Brown physician-scientists bridge academic divides to improve the lives of people with brain disorders.
At first glance Judy Liu, MD, PhD, and Eric Morrow, MD, PhD, don’t seem to have much in common. She’s a neurologist, he’s a psychiatrist and geneticist. She studies and treats epilepsy, while his research and clinical work center around autism spectrum disorder.
But the two have research roots in common—they met while completing their postdoctoral fellowships at Harvard Medical School in the 2000s—and both enjoy the intellectual challenge and inspiration of working at bench and bedside. Over the years they’ve occasionally been able to collaborate, she from George Washington University, he from Brown.
Then, last fall, Liu moved to Providence, recruited to the Medical School and Brown’s Laboratories for Molecular Medicine, where she set up her lab just down the hall from Morrow’s. They’re thrilled for the research opportunities their proximity will bring.
“We work on very similar problems, but they have different names,” says Liu, an assistant professor of neurology and of molecular biology, cell biology, and biochemistry. “By combining forces we can really make a lot of headway into all these problems, really push some science forward.”
Morrow and Liu stress that their work is, first and foremost, patient based. “There’s a very, very strong sense in both of our research programs that basic science work is a required prerequisite,” says Morrow, an associate professor of biology and of psychiatry and human behavior. “We’re both in the patient realm and in the basic science realm. We’re trying to go back and forth—ultimately, to bring things back to the patients.”
Morrow, who sees patients at Bradley Hospital, says he turned to genetics to identify mutations and better understand the biology of developmental conditions like autism. Just in the past five years scientists have found dozens of such mutations, he says.
“Now patients with autism, intellectual disability, epilepsy get their genome sequenced as a part of their genetic diagnosis,” Morrow says; up to 30 percent of patients with autism have a genetic subtype for their conditions. “We now have traction to study the biology of these very enigmatic disorders that, otherwise, were not so approachable. … So there’s a huge new wave of hope that comes from understanding the condition at much more of a biological level.”
Once scientists know a mutation, he says, they can make animal models that have it, generate stem cells from patients with the mutation, study the cells and neural pathways, and test therapeutic targets before embarking on expensive, difficult clinical trials. It makes precision medicine possible.
“The way you choose [epilepsy]medications is based on the side effect profile and tolerability. We don’t necessarily match the medicine with the cause of the disease,” says Liu, who will treat patients at Rhode Island Hospital. “The failure rate is about 30 percent. This is a very common neurological disease. … That means there’s over a million people in the US with seizures that aren’t adequately treated. In both autism and childhood epilepsy, a large proportion of cases are due to identifiable genetic causes.”
Epilepsy brought Liu and Morrow into the same research orbit. “I’ve always wanted to study epilepsy comorbidities,” Liu says. “People with epilepsy, as the seizures get worse and worse, they become more and more cognitively impaired. But we work on controlling seizures and not necessarily the cognitive problems.”
Nearly a third of people affected by autism or similar intellectual disabilities also have epilepsy. “These are not freestanding disorders,” Morrow says. For example, individuals with Christianson syndrome, a rare, X-linked condition that he studies, all have epilepsy. His early research on the disorder gave him and Liu a chance to work together again.
“Once he realized that all of the Christianson patients had epilepsy, he really wanted somebody who worked on epilepsy to be a close collaborator,” Liu says. “It’s very, very helpful to be closely related to a lab that is interested in the intellectual disability, the psychiatric aspects of these disorders. The same structures in the brain are important for both.” She adds, “As a doctor, it’s important for me to understand not just the one symptom, but to have a whole view.”
Rare diseases like Christianson syndrome inform scientists’ understanding of more common conditions. Twenty to 30 percent of autism is composed of individually rare genetic conditions, Morrow says—but each mutation is an opportunity to study the biology and “understand the themes.”
“There might be hundreds of different genes, but there are going to be fewer mechanisms because they’re related to each other in the molecular pathways,” he says. “So finding the points of convergence is a huge theme in the research. … Environment matters, people’s experience matters, but gene changes are very, very strong contributors that provide a powerful approach to study the mechanism.”
Morrow and Liu argue that the separation between neurology and psychiatry is an arbitrary one. “It’s all in the brain,” Morrow says. “If the person seizes they go to the neurologist. But if the person has abnormal behavior they’ll go to the child psychiatrist. But it’s really the same underlying problem.” People with epilepsy are prone to severe depression, he says, and the biology underlying the two conditions may be the same. “I think a lot of the treatments will be shared across disorders,” he says.
“They are, because anticonvulsants are used in psychiatry all the time as mood stabilizers,” Liu says. Combined neurology/psychiatry training programs have fallen out of favor, she adds, “but in the lab, it’s quite apparent that the research should be done with both points of view.”
Liu and Morrow are committed to bringing their disciplines together, and to a seamless flow between basic science and clinical medicine as well. To foster translational science, people must speak and understand both languages, Morrow says. “We’re two MD-PhD leaders of the lab groups, but our lab environment is filled with trainees who flow across these dualities”: PhDs and MDs, postdocs and medical fellows, undergrads and med students and grad students. “It’s a very special environment for trainees,” he says.
“Having a mixed environment is extremely powerful because it makes the trainees realize that there really shouldn’t be walls, so they’re not afraid to go over to the hospital, and even develop collaborations independently,” Liu says. “By working together we’re bridging pretty much every gap you can think of.”
