Aim of the project

We're pleased to have facilitated this Fellowship to develop academic and research links between the Chinese University of Hong Kong (CUHK) and the University of Cambridge. 
Dr Dwaipayan Adhya studied the interaction of testosterone and estradiol on developing neurons from typically developing and autistic individuals.

Importance of research

Autism is a complex genetic condition, with hormone and epigenetic components triggering risk genes. This study addressed this by looking at effects of hormones on autism-associated genes, enabling the discovery of novel genes that might play a greater role on the transcriptional level to contribute to the phenotype of the condition. Does this have translational importance to better clinical diagnosis in infants at risk of autism?

Scientists involved

  • Dr Dwaipayan Adhya

Key findings

The following outcomes were achieved:

  1. A prenatal hormonal milieu mimicking gestational steroidal levels was modelled using induced pluripotent stem cells (iPSCs).
  2. The effect of testosterone on global gene expression was investigated.
  3. Effect of testosterone on the androgen receptor was assessed.
  4. Novel genomic mutations and differentially expressed genes in autism were investigated.
  5. Caveats of working with iPSCs was investigated, such as heterogeneity and variability.
  6. Differentiating iPSCs were characterised for neuroprogenitor fate acquirement in autism.

 

How will the findings from this research help autistic people and their families?

Although these findings will not have immediate benefit to autistic people and their families, understanding the biology of autism is essential to understand the condition better and develop targeted therapeutic measures to ameliorate its symptoms. For example, it is now well known that there is presence of immune dysregulation in autism. This project has enabled us to understand the immune component in autism. Future studies will help develop therapies to reduce immune and inflammatory reactions which occur due to mutations in autism risk genes.

 

What research could this lead to?

This research will lead to several iPSC-based studies to understand convergent cellular behaviour in autism. This is important to understand how a heterogeneous genetic background may lead to common phenotypes, and if cellular phenotypes also occur in a spectrum similar to behavioural phenotypes. This study also leads to understanding the difference between syndromic and non-syndromic autism, e.g., the role of mutations in a highly associated gene such as NRXN1 versus mutations in several low risk genes.

 

List of publications

Adhya, Dwaipayan, et al. "Understanding role of steroids in typical and atypical brain development: Advantages of using a “brain in a dish” approach." Journal of Neuroendocrinology (2017).