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The Huang lab is interested in studying the molecular, cellular, circuit, and behavioral functions of genes involved in autism spectrum disorders (ASDs), neuropsychiatric disorders, and epilepsy. We currently focus on Smith-Magenis syndrome (SMS) and Tuberous Sclerosis complex (TSC), two childhood developmental disorders caused by loss of Retinoic Acid Induced 1 (RAI1) and TSC2, respectively. Both disorders are associated with intellectual disability, ASD, neuropsychiatric features, and severe epilepsy.
Our early work discovered the molecular function of Rai1 and pinpointed specific cell types underlying SMS-like neurobehavioral features (Huang WH et al., Neuron, 2016). We were also the first to demonstrate the reversibility of SMS-like symptoms in Rai1 haploinsufficient mice (Huang WH et al., PNAS, 2018). Currently, we apply modern molecular and neuroscience techniques to decipher the molecular and neural functions of Rai1 and Tsc2 in order to develop disease-modifying therapies. Currently, we are interested in the following areas:
Our early work discovered the molecular function of Rai1 and pinpointed specific cell types underlying SMS-like neurobehavioral features (Huang WH et al., Neuron, 2016). We were also the first to demonstrate the reversibility of SMS-like symptoms in Rai1 haploinsufficient mice (Huang WH et al., PNAS, 2018). Currently, we apply modern molecular and neuroscience techniques to decipher the molecular and neural functions of Rai1 and Tsc2 in order to develop disease-modifying therapies. Currently, we are interested in the following areas:
How do ASD-risk genes impair neural activity, wiring, and circuit function?
To answer this question, we will use modern neuroscience technologies including ex vivo and in vivo electrophysiology, calcium imaging, brain structural and metabolism imaging, viral-mediated circuit tracing, whole brain clearing and imaging, optogenetic, and neurobehavioral assays to study how ASD-risk genes alter neural functions from molecular to behavioral levels
To answer this question, we will use modern neuroscience technologies including ex vivo and in vivo electrophysiology, calcium imaging, brain structural and metabolism imaging, viral-mediated circuit tracing, whole brain clearing and imaging, optogenetic, and neurobehavioral assays to study how ASD-risk genes alter neural functions from molecular to behavioral levels
How do somatic mosaic mutations cause autism, psychiatric features, and epilepsy?
It is clear that many ASDs are caused by somatic mosaic mutations, such as how loss of heterozygosity (LOH). To understand how mosaic gene deletions drive ASD/epilepsy, we use an elegant genetic approach invented by my postdoc lab at Stanford, mosaic analysis of double markers (MADM), to perform single-cell analysis and dissect the cell-autonomous v.s. non-cell-autonomous functions of ASD-risk genes in neuronal development and dysfunction
It is clear that many ASDs are caused by somatic mosaic mutations, such as how loss of heterozygosity (LOH). To understand how mosaic gene deletions drive ASD/epilepsy, we use an elegant genetic approach invented by my postdoc lab at Stanford, mosaic analysis of double markers (MADM), to perform single-cell analysis and dissect the cell-autonomous v.s. non-cell-autonomous functions of ASD-risk genes in neuronal development and dysfunction
Identify molecular targets to treat ASD and psychiatric disorders associated with gene dosage imbalance
There are >600 human disorders associated with decreased gene expression (haploinsufficiency). We use cutting-edge CRISPR, genomic, transcriptomic, and proteomic approaches to identify therapeutic targets to correct symptoms associated with gene dosage imbalance to treat ASDs and epilepsy. Potential therapeutic targets include protein stability modifiers, promoters, and downstream targets of the disease-causing genes. Our recent work found that genetically increasing Bdnf signaling could prevent the development of SMS-like features in mice (Javed et al., Hum Mol Genet, 2021)
There are >600 human disorders associated with decreased gene expression (haploinsufficiency). We use cutting-edge CRISPR, genomic, transcriptomic, and proteomic approaches to identify therapeutic targets to correct symptoms associated with gene dosage imbalance to treat ASDs and epilepsy. Potential therapeutic targets include protein stability modifiers, promoters, and downstream targets of the disease-causing genes. Our recent work found that genetically increasing Bdnf signaling could prevent the development of SMS-like features in mice (Javed et al., Hum Mol Genet, 2021)
We thank our funding sources that made our work possible
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