Project 8p Research Newsletter - September 2023
💬 Research Question of the Month
Do you know a researcher who should be part of the Project 8p Research Network?
Let us know in the Comments section below!
🔬Research Highlight - The Project 8p Research Network
This month we are highlighting some of the talented researchers who are a part of the Project 8p Research network. They each bring unique expertise and perspective to their fields and to chromosome 8p disorder research.
Dr. Alysson Muotri - Professor, Departments of Pediatrics and Cellular & Molecular Medicine, School of Medicine, University of California, San Diego.
Dr. Muotri’s lab studies the evolution and development of the human brain using human stem cell models, brain organoids, electrophysiological recordings, and genomics techniques. He has made important contributions to the field of autism research and his partnerships with multiple rare diseases foundations, including the Loulou Foundation, Pitt-Hopkins Research Foundation, and the Rett Syndrome Research Trust, have led to the development of disease models that will help these communities better understand their disorders, and ultimately develop therapeutic treatments (Marchetto et al. 2010, Urresti et al. 2021, Wu et al. 2022).
Currently, Dr. Muotri’s lab is using cortical organoids derived from 8p families to better understand which cell types drive 8p neurodevelopmental phenotypes. Already this work has uncovered a potential key player in the pathobiology of 8p, a gene called RELN.
Dr. Muotri was a 2002 Pew Fellow, and is the recipient of numerous NIH grants and awards, including the NIH Director’s New Innovator Award, NARSAD, Emerald Foundation Young Investigator Award, Surugadai Award, Rock Star of Innovation, NIH EUREKA Award, and two Telly Awards for Excellence in Science Communication. Dr. Mutori will co-lead the newly launched UCSD Gene Therapy Initiative.
Learn more about Dr. Muotri and his research:
Modeling 8p with human brain organoids (Project 8p Research Roundtable, September 2022)
Alysson Muotri: A Brain Begins - in a Dish (Science Clear+Vivid podcast with Alan Alda)
Dr. Jason Sheltzer - Assistant Professor of Surgery (Oncology) and Genetics, Yale School of Medicine.
Dr. Sheltzer began studying aneuploidy in cancer as a postdoctoral fellow in the lab of the late Dr. Angelica Amon at MIT. Since then, he has made important contributions to the field of cancer research, identifying drivers of cancer resistance (Lukow et al. 2021) and prognosis (Smith and Sheltzer 2022), highlighting oversights in drug development (Lin et al. 2019, Bhattacharjee et al. 2022, Médard and Sheltzer 2023, The New York Times), and developing and employing novel CRISPR techniques to identify cancer’s genetic dependencies (Girish et al. 2023, Yale News). He has also published multiple papers on the topic of gender disparities in STEM (Sheltzer and Smith 2014, Sheltzer 2018, Greider et al. 2019, The Washington Post).
Now, Dr. Sheltzer is applying his deep knowledge of aneuploidy and experience with cutting-edge CRISPR techniques to chromosome 8p disorders. Using multiple techniques, his lab will attempt to restore disomy to 8p iPS cells in order to generate genetically matched 8p and control lines, which will serve as an important model for further research and drug screens. This work will also shed light on the possibility of chromosome engineering as a therapeutic strategy.
Dr. Sheltzer has been awarded the Gilula Prize from the American Society for Cell Biology, the Presidential Early-Career Science and Engineering Award, and was named one of Forbes Magazine’s 30 under 30 in Science (2015). Dr. Sheltzer is also a co-founder of the biotech startup Meliora Therapeutics, which has raised $11M in seed funding to develop mechanism-focused oncology drugs.
Learn more about Dr. Sheltzer’s research:
Chromosome Engineering to Restore Disomy in 8p iPS Cells (Project 8p Research Roundtable, June 2023)
Dr. Stefan Pinter - Assistant Professor, Genetics and Genome Sciences, Institute for Systems Genomics, University of Connecticut.
Dr. Pinter did his postdoctoral work in the Harvard lab of Dr. Jeannie Lee, a pioneer in the field of long noncoding RNA. There he became an expert in X chromosome inactivation (Pinter et al. 2012, Simon et al. 2013, Pinter 2016, Bansal et al. 2020, Bansal et al. 2021). Now, at the University of Connecticut, his lab is applying tools like XIST and CRISPR to study the developmental impact of changes in gene dosage in aneuploidy disorders like Trisomy 21 and Turner Syndrome (Ahern et al. 2022, Ahern et al. 2023, Bansal et al. 2023). His experience thinking about aneuploidy, complex modes of gene regulation, and in developing gold-standard iPSC-derived models are a huge asset to the 8p research network.
Dr. Pinter’s lab is currently working on a project to equip 8p and euploid iPS cells with inducible NGN2, to drive neuronal differentiation, and inducible CRISPR constructs capable of turning gene expression on (CRISPRa) or off (CRISPRi) in a targeted fashion. These tools will be used to dissect the impact of changes in gene dosage of individual 8p genes.
Dr. Pinter is a recipient of the prestigious NIH MIRA Award. He has also received the Centennial Award for Molecular Genetics from The Genetics Society of America for his outstanding research article “Allelic Imbalance Is a Prevalent and Tissue-Specific Feature of the Mouse Transcriptome” (Pinter et al. Genetics 2015), and has received fellowships from Massachusetts General Hospital and the German Research Foundation (DFG).
Learn more about Dr. Pinter’s research:
CRISPRa/i tools to probe gene function in 8p research (Project 8p Research Roundtable, May 2023)
💜 Family Corner
📆 Upcoming Events
8p Research Roundtable, September 25th, 1:30 PM EST. Email whitney@perlara.com if you would like to attend.
Dr Solveig Heide, Roseline Vibert, Professor Caroline Desombre