The Huang lab is interested in studying 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), as well as tuberous sclerosis, caused by loss of TSC1/2. Both disorders are associated with intellectual disability, ASD, and severe epilepsy. We will apply modern molecular and neuroscience techniques to decipher the molecular and neural functions of RAI1 and TSC2. 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 electrophysiology, calcium 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 
Picture

​
​
 How do somatic mosaic mutations cause autism and epilepsy?

It is clear that many ASDs are caused by somatic mosaic mutations, in the case of TSC, loss of heterozygosity (LOH) is involved. To address this question, we will use an elegant genetic approach, 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 neural development ​and dysfunction
Identify molecular targets to treat ASDs associated with gene dosage imbalance

There are >600 human disorders associated with decreased gene expression (haploinsufficiency). We will use cutting-edge 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 gene.

We thank our funding sources that made our work possible