Love of Science ‘Important, Exciting, and Beautiful’: Q&A With Ethan Goldberg, MD, PhD

Ethan Goldberg, MD, PhD

Editor's Note: Welcome to our monthly Faculty Spotlight series, in which we sit down with faculty members at Children's Hospital of Philadelphia Research Institute to learn more about their research and roles. Through these spotlights, our readers meet the diverse, dedicated, and distinctive individuals who lead our research community in our mission to improve children's health. It's a new round of spotlights and this time, we'll be asking our featured scientists about how they encourage diversity, equity, and inclusion within their labs. In this Q&A, we meet Ethan Goldberg, MD, PhD, physician in the Department of Pediatrics and director of the Epilepsy Neurogenetics Initiative (ENGIN). Stay tuned for more from our Faculty Spotlight series throughout this year!

How long have you been at CHOP?

I joined CHOP in 2008 as an intern as part of the five-year child neurology residency program here, which includes two years of general pediatrics followed by three years of training in child and adult neurology. I transitioned to the clinical faculty in 2013 and was subsequently appointed assistant professor in the Division of Neurology at CHOP and Departments of Neurology and Neuroscience at Penn in 2015, at which time I started my own independent basic science research laboratory.

Tell us a little about your research specialty.

My lab studies basic mechanisms of seizures and epilepsy in experimental model systems. Epilepsy is a disorder defined by recurrent seizures, which are abnormal hypersynchronous patterns of electrical activity in the brain. My particular interest is in a class of molecules called ion channels, which control the electrical activity of individual neurons. At least half of childhood epilepsy has a genetic component, and it is perhaps not surprising that genetic variation in ion channels is an important cause of epilepsy.

How does the diversity of neuronal cell types and their interconnections form brain circuits to process information? How does the interplay of ion channels, neurons, and circuits yield behavior, and how do such processes go awry in epilepsy and other neurological disorders? In the lab, we record electrical activity directly (using a technique called electrophysiology) and indirectly (using dynamic imaging methods) and manipulate activity using optogenetics in a range of model systems, including human neurons generated from induced pluripotent stem cells from human patients with epilepsy as well as transgenic mouse models of human epilepsy.

Why did you choose to focus on that specialty?

After finishing a PhD in Neuroscience in 2006, I returned to the wards to complete the clinical component of a combined MD/PhD program. During the required rotation in pediatrics, I happened to be assigned to the pediatric neurology unit and encountered children with severe epilepsy for the first time. This was right after the sequencing of the human genome, so we didn't know much about the genetic basis of epilepsy and only a small handful of epilepsy genes had been identified. However, I knew from my PhD work that genetic manipulation of ion channels produced epilepsy in animal models and that the few known human epilepsy genes in fact were ion channel genes. I saw the potential of building a career at the intersection of ion channels, genetics, and brain development, and was encouraged to pursue this idea by a mentor at that time, the late Ruth Nass, MD, professor of neurology, psychiatry, and pediatrics at NYU Langone, who took an interest in my career.

Can you describe a current or recent research project that you are excited about?

The lab is extremely fortunate to be filled with many talented trainees and staff, and we work together to pursue a range of exciting projects.

The lab is currently studying the mechanistic basis of febrile seizures, which is the most common type of seizure. The majority of febrile seizures occur between 12 and 18 months of age but are not observed beyond the age of 5 years. While often viewed as benign, prolonged febrile seizures remain a risk factor for future epilepsy and can in some cases be fatal. Despite this, we still don't understand how increased temperature triggers a seizure or why febrile seizures only occur during a specific developmental window.

Another project follows our recent discovery that genetic variants in the gene SCN3A encoding a specific sodium ion channel called Nav1.3 cause a form of severe early-onset epilepsy. What is particularly fascinating about this condition is that the majority of patients also have a congenital brain malformation. We are studying how variants in an ion channel thought to control electrical activity might lead to abnormal brain development and a structural brain malformation.

What are the long-term research questions you hope to answer?

The long-term goal of my laboratory is to understand the diversity and function of ion channels and of cerebral cortex cell types and circuits, and how genetic variation in ion channels leads to brain circuit dysfunction that underlies epilepsy and other neurodevelopmental disorders. The ultimate goal is to leverage scientific discoveries in these areas of inquiry toward the development of novel treatments to improve the lives of children with epilepsy.

How has mentorship impacted your career? Why do you believe mentoring is important in science?

Mentorship has been critical to my education and career development, and it has come in many forms and in many settings. My most important scientific mentors have been the heads of the labs where I trained, including Solomon Snyder, MD, at Johns Hopkins; Bernardo Rudy, MD, PhD, at NYU; and Douglas Coulter, PhD, here at CHOP. These were the people who fostered in me a love of science as important, exciting and beautiful, and who helped me discover where I might fit in this vast human endeavor. Serving as a mentor to the next generation of neuroscientists is most definitely the favorite aspect of my work.

What are some of the ways that you support diversity, equity, and inclusion (DEI) among your research team?

Building diversity and inclusion in science is a long-term process that should be approached at many levels: There is no "quick fix." I am personally committed to fostering diversity through mentorship and sponsorship of diverse neuroscience trainees. I serve as Chair of the Neuroscience Graduate Group MD/PhD Admission Committee, charged with interviewing and recommending applicants for admission to Penn's MD/PhD Program, and I have made DEI a high priority for my tenure on this committee. I personally mentor diverse trainees and staff, including those who identify as under-represented minorities (URM) or first-generation, low-income (FGLI), LGBTQ+, or who are living with a disability. It is a constant inspiration to me to interact with talented young people who enrich our shared mission with their unique perspectives.