Project 8p Research Newsletter
Welcome to the Project 8p Research Newsletter!
8p research is on the move in 2023. Last year we assembled a mission-driven team of researchers and clinicians focused on different segments of the Two-Year Research Plan, as explained below. As highlighted in the next section, two research projects that got underway last year are producing thought-provoking preliminary results. If you want to stay up to date on the leading edge of 8p research, please subscribe!
Dr Ethan Perlstein, PhD.
Director of Research @ Project 8p
Research Question of the Month
What if we could use 8p hero skin cells to identify potential drug repurposing treatments?
Research Highlight - January Research Roundtable
Dr. Nicoleta Moisoi is investigating mitochondrial dysfunction and DNA damage and repair in 8p fibroblasts in order to identify phenotypes that could be used for drug repurposing screens. During the January roundtable Dr. Moisoi showed that
8p fibroblasts are more resistant to cell death and exhibit lower levels of stress markers
8p fibroblasts accumulate more DNA damage
Cell painting showed distinct organellar features in 8p fibroblasts compared to controls
Dr. Alysson Muotri is growing cortical organoids derived from 8p family iPSCs to better understand the effects of the CNVs on early brain development. Dr. Muotri shared his recent results from single-cell sequencing of 1-month-old 8p cortical organoids, which showed that
8p organoids are smaller than control organoids and have fewer dividing cells
8p organoids show distinct populations of cells not found in control organoids
Watch the January Roundtable on the Project 8p YouTube channel:
Featured images above:
Left: Staining of DNA damage markers in fibroblast nuclei. Dr. Nicoleta Moisoi, De Montefort University
Right: t-SNE of single-cell sequencing from brain organoids. Dr. Alysson Muotri, UCSD
Project 8p Researcher Network and Two-Year Research Plan
The Project 8p Research Plan features four major research segments, with a fifth to be added soon:
💊 Drug Repurposing
🧠 Disease Modeling
🧬 Chromosome Therapies
💟 In-Hero Studies
💬 Assistive Technology - Coming Soon!
📃 Read the whole Research Plan on Substack
Recent Relevant Publications
The impact of 22q11.2 copy-number variants on human traits in the general population. Zamariolli, M. et al. AJHG (2023). https://doi.org/10.1016/j.ajhg.2023.01.005
This paper provides new evidence of incomplete penetrance and variable expressivity of 22q11.2 CNVs. Similar analysis of 8p CNVs is needed and would shed light on whether a top-down or bottom-up drug repurposing approach might be more successful.
The contribution of copy number variants to psychiatric symptoms and cognitive ability. Mollon, J. et al. Mol Psychiatry (2023). https://doi.org/10.1038/s41380-023-01978-4
This review article provides a nice overview of the relationship between different CNVs and various neurological disorders and includes discussion of potential mechanisms of incomplete penetrance and variable expressivity.
Neurodevelopmental copy-number variants: A roadmap to improving outcomes by uniting patient advocates, researchers, and clinicians for collective impact. Commission on Novel Technologies for Neurodevelopmental Copy Number Variants. AJHG (2022). https://doi.org/10.1016/j.ajhg.2022.07.003
Last year, the Commission on Novel Technologies for Neurodevelopmental CNVs, of which Project 8p is a part, outlined their collaborative, team science approach to accelerate CNV research.
Let us know if you’ve read or published a paper recently that you think the 8p community should know about!
Family Corner
The My Hero Initiative was created by Project 8p to support our patient driven goals. The My Hero Initiative includes all existing programs and partnerships that involve data and biospecimen collection, aggregation and analysis. Currently, there are 3 components (puzzle pieces) to the My Hero Initiative:
Please contact Kaiti Syverson (kaiti@project8p.org), Patient Engagement manager and 8p mother to enroll.
Upcoming Events
8p Research Roundtable, Dr. Ethan Perlstein February 27th, 1:30 PM EST
Gordon Research Conference on Functional Genomics of Human Brain Development and Disease April 2nd-7th, Ventura, CA. Ethan will be there - let us know if you will be too!
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Founded in November 2018 as a 501(c)(3) nonprofit, Project 8p Foundation works to empower a unified community for chromosome 8p heroes for a meaningful life today while accelerating treatments for tomorrow.