In this month’s Science with Sara blog entry, I’ve asked two researchers from the University of Washington & Seattle Children’s Research Institute — whose work falls under the broad area of the Biology Underlying ASD – to highlight an important or informative review or summary paper from their field.

Dr. Stephen Smith PhD is an Assistant Professor at the UW and Seattle Children’s Research Institute. His work focuses on how proteins located at the junctions between brain cells (called synapses) work or, in the case of neurodevelopmental disorders, why they might malfunction. Dr. Smith uses multiple animal models of ASD in order to understand how different genetic variants impact synapse function, and in turn, how this changes how a person learns and remembers.

Dr. Smith’s Pick:
• Sestan, N., & State, M. W. (2018). Lost in Translation: Traversing the Complex Path from Genomics to Therapeutics in Autism Spectrum Disorder. Neuron, 100(2), 406-423.

“This beast of a review paper is co-authored by Dr. Matthew State, who has been at the forefront of gene discovery in Autism for many years. I hesitate to recommend this paper for a non-specialist audience because it is so dense, but its depth and quality make it worth the effort. While it’s a bit heavy on the details of the genetics (Dr. State is a geneticist, after all), the main takeaway is that, after many years of gene discovery, we are beginning to understand the central pathways that are disrupted in autism- neuronal signaling, dynamic control of DNA translation, and how those processes play central roles in development. State and his co-author Dr. Nenad Sestan then discuss future efforts to understand how mutated genes lead to atypical behavior. Although this is clearly a difficult path, they outline a plausible route that many research groups, including mine, will be taking in the years ahead.“

You can find a full list of Dr. State’s work on

Dr. Smith’s website provides updates on the work in his lab.

Dr. Smita Yadav PhD is an Assistant Professor in Pharmacology at the UW. Her work focuses on neuronal networks (networks of brain cells) and specifically on how molecules regulate communication between brain cells. One focus of Dr. Yadav’s research is in the 16p11.2 genetic location – there are 29 genes that are in this region of our DNA, and structural changes to this area of our DNA are associated with both ASD and schizophrenia.

Dr. Yadav’s pick:
• Quesnel-Vallières, M., Weatheritt, R. J., Cordes, S. P., & Blencowe, B. J. (2018). Autism spectrum disorder: insights into convergent mechanisms from transcriptomics. Nature Reviews Genetics, 1.

“The first one is a review about understanding the ~75% non-syndromic, idiopathic cases of autism. The authors argue that a common pathway is emerging from transcriptome analyses that implicates RNA processing in ASD. The evidence includes: (1) cortical patterning of gene expression is lost in autism; (2) mRNA, lncRNA, miRNA and other non-coding RNA programmes are disrupted in ASD; (3) subsets of mRNAs regulating neuronal processes are consistently downregulated in individuals with ASD; and (4) RNA splicing regulatory programmes disrupted in ASD are responsive to neuronal activity and, conversely, affect neuronal activity.”

• Amin, N. D., & Paşca, S. P. (2018). Building models of brain disorders with three-dimensional organoids. Neuron, 100(2), 389-405.

“The second paper is a review on using 3D brain organoids to model neuropsychiatric diseases. While this review is not specific to autism, in my view, this space is where a lot of the research on the biological basis of autism will be in the future. The different kinds of organoids and the questions that we can now ask are quite amazing. Some caveats of this technology remain.”

Additional References

IACC Office of Autism Research Coordination Summary of Advances in Autism Spectrum Disorder Research: Calendar Year 2017. Question 2: What is the Biology Underlying ASD?

IACC Office of Autism Research Coordination Strategic Plan For Autism Spectrum Disorder Research 2016-2017 Update. Question 2: What is the Biology Underlying ASD?