Never forget that humility is the mark of greatness
Welcome to The Short Read, our weekly peek behind the curtain at the people who make this amazing community tick. Make sure to check back every Tuesday for the latest installment.

Hsiao-Tuan Chao

Hsiao-Tuan Chao

Hsiao-Tuan Chao started her academic career at the University of Texas, where she completed a Bachelor’s degree in Biochemistry, before moving to the Baylor College of Medicine for an MD and PhD. While she completes her Postdoc at Baylor, Tuan is working to understand the childhood, neurological condition Rett syndrome. In particular, she’s focused herself on how small genetic variations can influence the way in which our neurons can talk to one another, and how that can influence the way we communicate in turn.

It’s been her work in this area that led to her being named one of the 2017 STAT Wunderkinds!


What are you working on right now?

Through an international collaborative effort based at the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and Baylor College of Medicine with the National Institutes of Health Undiagnosed Diseases Network, we recently found the genetic basis for a childhood neurologic condition known as the Hypotonia, Ataxia, and Developmental Disorder Syndrome (HADDS) in a study published in the American Journal of Human Genetics. Our team identified multiple unrelated individuals with recurrent de novo missense mutations affecting a highly evolutionarily conserved residue, p.Arg163, in the transcription factor EBF3 (Early B-Cell Factor 3) that is crucial for stabilizing the interaction between EBF3 and the target DNA sequence. Using fruit fly and cell-based models we showed that these missense mutations severely disrupt the ability for EBF3 to activate gene transcription, impair essential developmental processes, and are deleterious to survival. Other researchers concurrently identified similarly damaging EBF3 mutations or gene deletion in association with the same clinical features. We are now actively working to determine the molecular, cellular, and neural circuit level alterations associated with disrupted EBF3 function. These findings have the potential to provide key mechanistic insights that can be leveraged through translational research into therapeutic applications for many childhood neurodevelopmental disorders with similar clinical features and disease mechanisms, such as intellectual disability, autism, and epilepsy.


What’s the biggest challenge you face in your work at the moment?

As a child neurologist, I am acutely aware that for many neurological conditions we face the hurdle of determining how specific genetic alterations relate to the inherent complexity of the nervous system. Although the increasing pace of biomedical and technological advances have accelerated our understanding of many fundamental neurobiological processes, we are still scratching the surface with regards to elucidating how the inter-relationships between gene expression, neurons, glia, microglia, and other cell-types ultimately transform into our thoughts, emotions, and behaviours. Therefore, it is imperative that we identify and implement new strategies to efficiently integrate genetic findings with disease mechanisms at the molecular, cellular, neural circuit, and whole organism levels. Building multi-disciplinary collaborations and leveraging scientific approaches in a diverse range of animal models (fruit fly, zebrafish, mouse, etc) and cell-based approaches are key for accelerating disease-relevant genetic findings and “bench-side” discoveries into meaningful clinical applications.


Name one big development that you would like to see in your field the next 18 months.

There are many things on my wish-list for biological, technological, and analytical advances that would improve our understanding of the genetic underpinnings of complex neurologic disorders and how they relate to the development, maintenance, and plasticity of the nervous system. However, many of these advances will take far longer than 18 months to mature. But what would be achievable in 18 months is for the research, clinical, and technological communities to increase communication with the lay public through outreach activities about the value and necessity of supporting multi-disciplinary biomedical research. It is through community outreach and science education in the classrooms that we ensure continued public commitment to develop the innovations and creative thinking required to advance our ability to treat, and perhaps cure, many devastating human conditions.


What are you most proud of in your career?

As a physician-scientist in the field of child neurology, the ability to help a child and their family identify the reason for their neurologic ailment, effectively treat their symptoms, and see the child achieve new skills and abilities is one of the most rewarding aspects of my career. However, for many chronic childhood neurological disorders our ability to effectively halt, reverse, or even “cure” the disorder is all too limited. While it is deeply moving to return to the children and their families in my clinic and share with them the genetic clues into their ailments, it is also immensely humbling to know that there are still many hurdles to surmount as we traverse from a genetic diagnosis to a meaningful improvement in quality of life. Therefore, I remain fervently committed to the mentorship and training of young scientists and physician-scientists who will continue to advance our field with new ideas and innovations.


Which scientists, living, dead, or fictional, would you invite to dinner, and why?

There are so many physicians, scientists, scholars, and philosophers whose insight, foresight, and creativity formed the foundation for modern medicine and science that it is hard to select only a few. I would start with those who had the ability to observe the natural world (both seen and unseen), derive new concepts, and create new inventions that far exceeded their times. This would include ancient polymath physicians like Hippocrates and Hua Tuo who revolutionized the thought and practice of medicine and whose influence continues to resonate today. Joining them at the dinner table would be Nicolaus Copernicus, Charles Darwin, Barbara McClintock, Rosalind Franklin, Seymour Benzer, and Tu Youyou for their ability to study the natural world from new perspectives, challenge conventional beliefs through their discoveries, and transform their fields.


What advice do you wish someone had given you at the start of your career?

Enjoy the journey! We are so often caught up in the mad rush to achieve a set endpoint or meet a deadline that we forget that the joy of science is in the endless journey to ask new questions, discover new answers, and continue to be creative and innovative in our thinking and approaches. Keep an open mind for opportunities that may arise to tackle a new scientific direction, pursue novel approaches, and build fruitful collaborations.


Opinions and views expressed in The Short Read are the interviewee’s and not those of the home institution.

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