Azrieli Centre for Autism Research (ACAR): Transforming autism research, training and care -- improving lives via Open Science

Wei-Hsiang Huang

Wei-Hsiang Huang

Wei-Hsiang Huang is a neuroscientist at the Center for Research in Neuroscience (CRN) at the department of Neurology and Neurosurgery at McGill University.

He trained with the world-renowned child neurologist, Huda Zoghbi, at Baylor College of Medicine and Howard Hughes Medical Institute. There, he used electrophysiology, confocal imaging, and genetic mouse models to study the brainstem retrotrapezoid neurons, which have been long implicated in congenital central hypoventilation syndrome and sudden infant death syndrome.

He pursued postdoctoral training at Stanford University/HHMI with Liqun Luo, a leader in the field of neuroscience and genetic tool development. Huang created multiple mouse lines and incorporated neurobehavioral assays, cutting-edge neuroscience and genomic techniques to study how loss of Retinoic Acid Induced 1 (RAI1) causes Smith-Magenis Syndrome (SMS), a condition often linked with autism.

To identify therapeutic targets for SMS and related neurodevelopmental conditions, his lab is taking two complementary approaches:

  • Understand the molecular programs and neural functions regulated by RAI1 by dissecting its temporal and spatial functions;
  • Target the root of the condition by developing novel therapies to restore the gene dosage imbalance of SMS.

By studying RAI1 as a dosage-sensitive protein, his lab uses genetic animal and human cell models, molecular techniques, electrophysiology, calcium imaging, and neurobehavioral assays to elucidate its precise mechanisms of pathogenicity.

Q: What drives your research

A: I am interested in monogenic forms of syndromic autism. To me, it is remarkable that our intellect, cognition, and social function can be affected by mutations in a single gene. What are the functions of these genes during development and adulthood? What are the molecular, cellular, circuit, and behavioral functions of these genes?

By answering these are questions, I believe we will be closer to understanding ourselves as well as developing therapies for help-seeking patients affected with autism and other related conditions.

My lab studies the molecular, cellular, circuit, and behavioral functions of genes involved in autism spectrum disorders (ASDs) and epilepsy. We are currently focusing on Smith-Magenis Syndrome (SMS), a childhood developmental disorder caused by loss of Retinoic Acid Induced 1 (RAI1).

We apply modern molecular technique and neuroscience tools to decipher the molecular and neural functions of RAI1, and develop therapies using different experimental models from mice to human induced pluripotent stem cells.

Q: How will your research improve the lives of autistic individuals? 

A: My goal is to develop a cutting-edge research program that will ultimately improve quality of life for patients by studying the molecular and neural function of genes responsible for autism spectrum disorders, and developing disease-modifying therapies.

I am interested in combining my expertise in neurophysiology, molecular engineering techniques, brain imaging, neurobehavioral assays, and in vivo modeling to achieve this goal.

Q: How has ACAR helped to advance your research? 

A: Funding from ACAR helps us to generate advanced animal models for Smith-Magenis syndrome (SMS), which has tremendous potential for studying the developmental trajectories in brain function.

Our project has a high translational impact and provides a unique path towards the future development of therapeutic approaches to normalize RAI1 levels. 

Research Areas

Autism, Smith-Magenis syndrome, neurodevelopment, induced pluripotent stem cells, advanced animal models

Contact  

Email: wei-hsiang.huang [at] mcgill.ca

List of Selected Publications

Javed S, Lee YJ, Xu J, Huang WH Temporal dissection of Rai1 function reveals brain-derived neurotrophic factor as a potential therapeutic target for Smith-Magenis Syndrome Human Molecular Genetics, 2021 Aug 31;. doi: 10.1093/hmg/ddab245.

Huang WH*, Wang DC, Allen, WE, Klope M, Hu H, Shamloo M, Luo L* Early Intervention Reversed Abnormal Social Interaction in a Mouse Model of Smith-Magenis Syndrome PNAS, 2018, Oct 16;115(42):10744-10749. (*correspondence)

Yeh SY, Huang WH, Wang W, Ward CS, Chao ES, Wu Z, Tang B, Tang J, Sun JJ, van der Heijden ME, Gray PA, Xue M, Ray RS, Ren D, Zoghbi HY Respiratory Network Stability and Modulatory Response to Substance P Require Nalcn Neuron, 2017, Apr 19;94(2):294-303.e4.

Huang WH*, Guenthner CJ, Xu J, Nguyen N, Wilkinson AW, Gozani O, Chang HY, Shamloo M, Luo L* Molecular and Neural Functions of Rai1, The Causal Gene for Smith-Magenis Syndrome Neuron, 2016, Oct 19;92(2):392-406. (*correspondence)

Huang WH, Tupal S, Huang TW, Ward CS, Neul JL, Klisch TJ, Gray PA, Zoghbi HY Atoh1 governs the migration of postmitotic neurons that shape respiratory effectiveness at birth and chemoresponsiveness in adulthood Neuron, 2012, Sep 6; 75(5): 799-809.

 

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The Neuro (Montreal Neurological Institute-Hospital) is a bilingual academic healthcare institution.   We are a McGill research and teaching institute; delivering high-quality patient care, as part of the Neuroscience Mission of the McGill University Health Centre. We are proud to be a Killam Institution, supported by the Killam Trusts.

 

 

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