Identifying candidate psychiatric treatment targets from brain-enriched isoforms of CACNA1C

Voltage-gated calcium channels (VGCCs), including CACNA1C, are robustly linked to bipolar disorder and schizophrenia by genomic studies and are potential neuropsychiatric drug targets. However, VGCCs are also important in the cardiovascular system and existing drugs targeting these channels are used to treat high blood pressure. Therefore, we characterised the repertoire of isoforms of CACNA1C expressed in adult human brain, heart and aorta, as brain-enriched isoforms could be the targets for new brain-selective treatments. Using long-read RNA sequencing and a custom analysis pipeline, we identified many novel isoforms and demonstrated that splicing is highly tissue-specific. We discovered that alternatively spliced exons 21 and 22 are differentially expressed between the human brain and cardiovascular system. These exons are already known to influence drug response and therefore could be the target for tissue-selective treatments.

About the Speaker 

Dr Nicola Hall is a postdoctoral fellow at the University of Oxford, Department of Psychiatry. She is using her background in molecular biology and RNA sequencing to investigate gene expression in the human brain. Her current work focuses on the tissue-specific alternative splicing of genes implicated in schizophrenia and bipolar disorder, using targeted sequencing to characterise transcripts and identify novel treatment targets. Nicola completed her PhD in 2017 at the University of Oxford, Department of Biochemistry.

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