PHILIP R. DODGE YOUNG INVESTIGATOR AWARD LECTURE: Molecular and Cellular Mechanisms of Excitation and Inhibition in Neurodevelopmental Disorders

Hsiao-Tuan Chao, M.D., Ph.D
Jan and Dan Duncan Neurological Research Institute, Houston, Texas, USA

The 2020 CNS Philip R. Dodge Young Investigator Award recipient is Hsiao-Tuan Chao, MD, PhD of Baylor College of Medicine (BCM). Tuan is an immensely talented individual who will be a leader in child neurology and in basic neuroscience of neurodevelopmental disorders. Her research has the potential to broaden our understanding of neural circuit development and function, with the long-term goal of advancing therapeutic strategies.

Dr. Chao, a native of Austin,Texas, was born to an engineer father (with a secret desire to be a neuroscientist) and a special education teacher mother. She spent much of her middle and high school years volunteering at her mother’s school, Rosedale, a beloved Austin Independent School District school for children with special needs. One of her mother’s favorite students was a young lady with constant hand wringing, who in retrospect probably had Rett Syndrome, a disorder that Dr. Chao would study for her PhD thesis. As student volunteers, Dr. Chao and her brother helped with daily care, therapies, and educational needs of her mother’s charges, while her father would make and donate equipment for therapy. Her brother serves as a career U.S. military officer and her mother retired from special education. Unfortunately, Dr. Chao lost her father early in 2020, but she continues to carry on his legacy. Her parents instilled in her a love of learning, a lifelong curiosity, and a service to others that comprise the foundation for an early promising career.

After completing her high school International Baccalaureate Diploma Program with honors in chemistry, physics and biology (top 1% of class, Presidential Award for Educational Excellence), she matriculated at the University of Texas at Austin (UT Austin) as a Plan II Honor’s College and Biochemistry double-major. With over 70 advanced credit hours, she entered as a sophomore and finished this challenging double major in only 3 years. It was at UT Austin where she first studied the mechanisms of fruit fly neurotransmitter release in the laboratory of Bing Zhang, PhD and met her future husband, Mingshan Xue, PhD, a neuroscientist at BCM.

Dr. Chao graduated summa cum laude with dual Bachelor of Arts and Bachelor of Science degrees from UT Austin and matriculated into BCM’s Medical Scientist Training Program as a McNair MSTP Scholar with The Robert and Janice McNair Foundation. She completed her PhD in Neuroscience with Christian Rosenmund, PhD and Huda Zoghbi, MD, where she made significant contributions to our understanding of excitatory and inhibitory neuronal mechanisms of disease in Rett and MECP2-duplication syndromes. Their research was among the first to uncover critical roles for MeCP2 in fine-tuning excitatory synaptic connections and regulating inhibitory neuronal signaling. The impacts of these discoveries are reflected by the 2020 Philip R. Dodge Young Investigator Award Hsiao-Tuan Chao, MD, PhD Profile by Gary D. Clark, MD Child Neurology Society | Fall 2020 17 thirteen publications resulting from Dr. Chao’s doctoral studies, including landmark first author publications in journals such as Nature and Neuron. The discovery linking disrupted inhibitory GABAergic signaling to Rett syndrome and to autism made a broad impact, and was recognized as one of the top 10 autism research findings of 2010 by Autism Speaks. In 2012, she graduated with her MD and PhD degrees and was selected to present the commencement address for the graduate school of biomedical sciences.

Dr. Chao completed her Child Neurology residency training in the Basic Neuroscience pathway at BCM and Texas Children’s Hospital (TCH) in 2017. During her residency training, she served as Chief Resident from 2015-2016, and in 2016, she joined the laboratory of Hugo J. Bellen, DVM, PhD at the Jan and Dan Duncan Neurological Research Institute (NRI) to pursue post-doctoral training in neurogenetics and fruit fly neurobiology. She was instrumental in an international collaborative effort with researchers in the Undiagnosed Diseases Network, BCM, and the NRI that co-discovered the association between genetic variations in EBF3 and a neurodevelopmental disorder manifesting in variable cognition, speech impediments, poor muscle tone, impaired coordination and autistic behaviors. The discovery was published in the American Journal of Human Genetics and the disorder is now known as the Hypotonia, Ataxia and Delayed Development (HADD) syndrome. This generated much excitement in the field as EBF3 was previously known to be an important meditator of inhibitory neuron development, further supporting the emerging theme of disrupted inhibitory neuronal signaling as a shared pathogenic mechanism for many neurodevelopmental disorders. To further expand our understanding of HADD syndrome, she established a multidisciplinary HADD syndrome clinic at Texas Children’s Hospital (TCH) that integrates the strengths of human genetics and neuroscience research at BCM. For this work, she received the Child Neurology Society Outstanding Junior Member Award, STAT News Wunderkind award, and post-doctoral research training fellowships from the Child Neurologist Career Development Program (CNCDP)-K12 and the American Academy of Neurology in 2017.

In 2017, while still a medical resident, Hurricane Harvey flooded her single-story house. While the floodwater rapidly rose, the unsinkable Dr. Chao, from her attic, uploaded her application for the prestigious NIH Director’s Early Independence Award (DP5), an R01-equivalent grant awarded to outstanding young scientists to accelerate their research independence. The DP5 award enabled her early transition to research independence, which was further supported by the Elterman PERF grant from the Child Neurology Foundation, and the Burroughs Wellcome Fund Career Award for Medical Scientists. In 2018, Dr. Chao established her independent research laboratory at the NRI as an Assistant Professor with joint primary appointments in the departments of Pediatrics, Division of Neurology and Developmental Neuroscience, and Molecular and Human Genetics at BCM, and was named a McNair Scholar. Her primary research focus is to elucidate the genetic and neural mechanisms underlying neurodevelopmental disorders such as autism, intellectual disability, and epilepsy through integrating human genetics with mechanistic studies of single gene disorders in fruit flies and mice.

Dr. Chao is an exemplary child neurologist, a rigorous scholar, and a remarkable physician-scientist. She is committed to advancing the growth of physician-scientists in child neurology. She encompasses the ideal qualities of a Philip R. Dodge Young Investigator, and her proposed research has tremendous potential to transform both our mechanistic understanding of neurodevelopmental disorders and our field.

Gary D. Clark, MD.