Editing the Brain @ University of Maryland School of Medicine
Congratulations to JaNýa Brown, who’s team won the grand prize at the 2024 D.C. Public Health Case Challenge at the National Academy of Medicine!!! Their proposal “Guiding Resilience and Offering Wellness (GROW)” came in at the top of this year’s competition on “A Public Health Approach to Address Substance Use and Mental Health Concerns Among Emerging Adults in the DMV Area”. Read all about it in the linked press release by the NAM!
Congrats to Bek Altas and other lab members, as well as our collaborators at the Max Planck Institute for Multidisciplinary Sciences and the University of Turin. Our paper on the synaptic localization of Neuroligin-3 in the mouse and human brain and the molecular mechanism that regulates it, became the cover article on this month’s issue of Biological Psychiatry! Congrats to Cheryl Brandenburg for the cover art and the epic experiment that inspired it, one of the first ever immunolabelings of excitatory and inhibitory synapses in the human brain!
Congrats to all involved in obtaining funding from the Maryland Stem Cell Research Fund. Our lab, in collaboration with the Ivy Dick lab, was awarded a 2-year MSCRF Launch grant titled “iPSC Platforms to Develop Genome Restoration Strategies Using Cas9-RC“.
The first study, led by the Mackis Lab at Harvard University and featured in Cell Reports, develops an approach for delivering genes, including Cas9, to select neural populations by in utero electroporation. This method achieves internally-controlled mosaicism that facilitates phenotype discovery in the developing brain.
The second paper, from the Suk Lab at UMSOM and published in ACS Nano, demonstrates our ability to target Cas9 mRNA to select foci in the adult brain. This was achieved through systemic delivery using lipid nanoparticles, coupled with localized targeting by microbubble-mediated focused ultrasound. This non-viral strategy represents a significant advance in treating adult brain disorders by enabling focal genome editing directly in the adult brain.
Together, these studies represent substantial progress in non-viral CRISPR delivery methods for both developing and adult brains. By expanding the in vivo CRISPR toolkit, we are laying the groundwork for the development of neural somatic cell genome editing as future genomic therapeutics.
Congratulations Luciano and Gijung!
Colin Robertson becomes the 3rd member of the lab to defend their PhD, in the historic Davidge Hall, the longest serving Medical Lecture Hall in America!
Colin defended his pioneering work in using Prime Editing, a reverse-transcriptase hybrid CRISPR technology, in the developing mouse brain to model individual patients with genetic epilepsies. Colin is staying on as a postdoc to translate these CRISPR technologies into clinical applications.
Congratulations Colin!!
Andrea Romanowski successfully defends her PhD work on developing CRIPSR tools for gene knockin in the embryonic rodent brain. Her unique combination of expertise in developmental neuroscience and in vivo genome editing got her recruited to the National Institutes of Mental Health in Bethesda, where she will do a postdoc in the lab of James Bourne!
Congratulations Andrea!!!
Our paper with Gene Blatt in Journal of Comparative Neurology on the evolution of neuroanatomical tracing methods came out today with Cheryl’s beautiful electroporated, cleared, and light sheet imaged hippocampus gracing the cover, alongside Dee Pandya’s India Ink traces. Happy New Year everyone!
Just out, our paper on the biology of a synaptic adhesion molecule critically implicated in autism, published in Biological Psychiatry!
This massive paper includes outstanding work from scientists and collaborators at the Max Planck Institute for Multidisciplinary Sciences in Germany, and the University of Turin in Italy. It includes some of the first ever imaging of human synapses (spot the cool cup-shaped presynaptic terminals nestled in the human brainstem ????!), and identifies a molecular mechanism that determines the synaptic localization and transmitter-specificity of Neuroligin-3 between excitatory and inhibitory synapses in the brain. Congrats to everyone involved, a great way to end the year!
For all genome editing fans out there, check out our latest study on bioRxiv showcasing in utero prime editing to model an epilepsy patient with an ultra-rare GRIN variant. To our knowledge, this marks a significant milestone as the first prime editing of neurons in vivo!
Led by Colin Robertson in our lab, alongside Patrick Davis from Boston Children’s Hospital and Harvard Medical School, this ambitious project aims to make precision medicine more accessible to a broad patient population. This rapid workflow to generate personalized animal models with prime editing we hope is a step toward enabling individuals with rare genetic epilepsies to test and tailor pharmacotherapy on their personalized models, reducing the burdens of exploring treatments.
A big thank you for the collaborative efforts of the team, including our partner UM-MIND labs of Peter Crino, Phil Iffland, Steffen Wolff, Brian Mathur, and Ivy Dick; as well as our wonderful collaborators from U Pitt, Eldin Jašarević, and UC Anschutz, Tracy Bale! Thank you all for this achievement and the fantastic collaboration we enjoy!
We look forward to this research advancing toward bedside-to-bench applications!
Congrats to Dr. Bek Altas and our collaborator Prof. Hiroshi Kawabe from Gunma University, Japan, who teased apart a complicated network of cellular interactions between neurons and glia in the brain that cause seizures. Mechanisms of proteostasis and downstream ion gradient homeostasis in astrocytes results in epileptiform network activity in neurons, possibly informing about the pathophysiology behind rare forms of epilepsy with gene variants of the ubiquitin pathway. Read all about it!