Loading Events
  • This event has passed.

« All Events

RNA Innovation Seminar: Carlos Cruchaga, Washington University in St Louis

Monday, January 30, 2023 @ 4:00 pm - 5:00 pm

“Role of Circular RNA in Alzheimer’s Disease”
Carlos Cruchaga, Ph.D.
Director, NeuroGenomics and Informatics Center
Washington University in St Louis

In-person: BSRB, ABC seminar rooms / hybrid link

Short Bio: Dr. Cruchaga is a human genomicist with expertise in multiomics, informatics, and neurodegeneration. He completed his PhD in Biochemistry & Molecular Biology in 2005 at the University of Navarra in Spain. During his first postdoc with Dr. Pastor he conducted statistical human genetics studies focused on Alzheimer’s disease (AD) and Parkinson’s disease (PD). He then moved to Dr. Goate’s Lab to complete his training in quantitative human genomics. Dr Cruchaga established his laboratory at Washington University in  2011 to study the genetic architecture of neurodegenerative diseases. His interests are focused on using human genomic and other -omis data (proteomics, metabolomics, & lipidomics) to identify and understand the biological processes that lead to AD, PD, frontotemporal dementia, and other neurodegenerative processes. He is the founding director of the NeuroGenomics and Informatics Center at Washington University.

Abstract: Circular RNAs (circRNAs) are a class of RNAs highly expressed in the nervous system and enriched in synaptoneurosomes. In Alzheimer Disease, synapse lost is one of the events implicated on disease. circRNA are form by back-splicing (head-to-tail splicing), and where first described in eukaryotic cells and other studies suggested that synapse could be enriched for circRNA. Based on we hypothesized that specific circRNA would be differentially expressed in AD cases compared to controls and that those effects could be detected early in the disease. We optimized and validated a novel analyses pipeline for circular RNAs (circRNA). We performed a three-stage study design to robustly identify circRNA associated with AD and AD-related phenotypes. Additional analyses were performed to demonstrate that the expression of circRNA were independent of the lineal form as well as the cell proportion that can confound results. Co-expression analyses of all the circRNA together with the lineal forms and found that circRNA, including those that were differentially expressed in Alzheimer disease compared to controls co-expressed with known causal Alzheimer genes, such as APP and PSEN1, indicating that some circRNA are also part of the causal pathway. We also demonstrated that cirRNAs brain expression explained more about Alzheimer clinical manifestations that the number of APOε4 alleles, suggesting that could be used as a potential biomarker for Alzheimer disease. In summary, we demonstrated for the first time that brain circular RNAs (circRNA) are part of the pathogenic events that lead to Alzheimer’s disease


Monday, January 30, 2023
4:00 pm - 5:00 pm