Kevin Ess, M.D., Ph.D., is Gerald M. Fenichel Chair in Neurology and associate professor of Pediatrics, Cell & Developmental Biology, and Neurology, as well as director of the Division of Pediatric Neurology. This year, he is serving as Committee Chair for the Vanderbilt Kennedy Center’s (VKC) 2019 Science Day.
Research in Ess’s lab is focused on deciphering the molecular mechanisms required for typical brain development and how disruptions of these processes lead to malformations of the cerebral cortex. Children with these aberrations typically suffer from severe seizure disorders such as epilepsy as well as severe cognitive and behavioral problems such as autism. To approach these complex neurologic disorders, Ess has been studying tuberous sclerosis complex (TSC), a disease that prominently features cortical malformations and is caused by loss of either the TSC1 or TSC2 genes. TSC is quite prevalent and is the most common genetic cause of seizures and autism in children. To study these complicated abnormalities of the human brain, Ess has generated experimental models of TSC using genetically engineered mice as well as in vitro progenitor cell systems. His long-term goal is to use these models to precisely define the molecular pathways used by the TSC1/2 genes during human brain development. This knowledge will facilitate the development of more efficacious therapies for children who have epilepsy or autism.
In the interview below, Ess shares what inspires his research in developmental disabilities, what he’s learned through his work, and how membership with the Vanderbilt Kennedy Center helps him achieve his goals.
Tell me about your attraction to developmental disabilities research. Do you have a personal connection to disability?
I became interested in developmental disabilities research during my Ph.D. training in Developmental Biology. I was interested in studying how the brain develops and wanted to study brain malformations, especially as relating to epilepsy and developmental disabilities. I was also very interested in genetics and emerging investigations about how aberrant cellular signaling pathways could alter brain development and presumably underlie neurological disorders. I don’t have a personal connection but have been immersed in taking care of children with developmental disabilities since I began my clinical training about 23 years ago.
What are your current research interests and what challenges do they address?
My research has focused on two genetic disorders, tuberous sclerosis complex (TSC) and alternating Hemiplegia of Childhood (AHC). TSC and AHC are clinically and genetically distinct, but patients with either disease frequently have seizures and intellectual disabilities. Our research approach for both diseases uses human induced pluripotent stem cell models we created from patients with this disease. We are also using genetic editing technologies to alter genes of interest in our stem cell models and then differentiating stem cells to specific populations of neurons and glia cells to better understand disease mechanisms at the cellular and molecular levels. This approach should allow us to identify key molecular determinants of disease that hopefully will lead to improved therapeutics.
Do you have a story that illustrates the impact of your work?
Over the last 10 years, rapid advances in stem cell technology and gene editing have transformed how scientists and clinicians can approach human diseases. We have attempted to keep abreast of these advances and collaborate with many of the exceptional faculty at Vanderbilt. This has led to new and exciting approaches using stem cell models to generate “higher order” neural structures that seem to better recapitulate human brain development. The use of all these technologies will further drive the impact of our work for children with developmental disabilities.
What are your reasons for becoming a Vanderbilt Kennedy Center (VKC) Member?
I came to Vanderbilt in 2006 well aware of the VKC. In fact it was a key part of my recruitment as I knew the developmental disability and greater neuroscience community it represented would be essential to my success. My clinical and research activities have been continually enhanced by the VKC both as a resource infrastructure and by ongoing collaborations.
Elizabeth Turner is associate director of VKC Communications.