British Society for Gene and Cell Therapy (BSGCT)’s Post

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare genetic #epilepsy. A theme of cell biology is redundancy: if a gene or protein is lost, there are often alternate pathways that can somewhat compensate, but the compensation is seldom 100%. Researchers found that the protein EB2, a key target of CDKL5, is also phosphorylated by another protein called CDKL2. The idea is to exploit this pathway redundancy by searching for ways to boost CDKL2 levels, hoping to sufficiently activate EB2 in the absence of CDKL5. This strategy of activating or enhancing an alternate biological pathway has led to breakthroughs in other genetic diseases, such as spinal muscular atrophy with nusinersen (Spinraza). Hope this strategy pays off in CDD and leads to treatments for other genetic epilepsies and diseases! +++ 👋 I’m Chris, a passionate medical writer, strategist, and founder of Quill Science LLC dedicated to bridging the gap between science and its impact with accurate and compelling narratives. 🌐 For a scientific partner led by curiosity and desire to improve health, please check out Quill Science and book a discovery call: www.quillscience.com

Leveraging patient cell transdifferentiation into induced neurons to enhance diagnostic yield for neurological genetic disorders, Pengfei Liu, PhD, FACMGG joins this month's journal club to present this innovative workflow for rare disease diagnostics using RNA-seq. During the live journal club event, Dr. Liu will cover: 🧬How transcriptome RNA-seq using accessible tissues can fall short in characterizing genes involved in neurological disorders. 💡The streamlining of cell transdifferentiation into a diagnostic RNA-seq workflow. 🥼The increased molecular diagnostic yield by activating neurological disease-associated genes and neuron-specific isoforms with induced neuron RNA-seq. Gain these insights on June 12 by registering today: https://lnkd.in/eeH-XUHJ #ASHG #HumanGenetics

"🧬 Groundbreaking Discovery! A recent study has unveiled mutations in a non-coding gene, RNU4-2, as a leading genetic cause of intellectual disability, impacting tens of thousands globally. This significant finding, emerging from collaborative efforts at Mount Sinai, University of Bristol, KU Leuven, and the NIHR BioResource, ranks just behind Rett syndrome in prevalence among neurodevelopmental disorders. Dive into the details of how this overlooked gene could reshape our approach to diagnosing and understanding intellectual disabilities. #Genetics #Neurodevelopment #Innovation"

I am pleased to share a new preprint from our lab. In this study, we demonstrated the scalable and robust differentiation of human pluripotent stem cells (hPSCs) into key subpopulations of hypothalamic arcuate nucleus (ARC) neurons, including proopiomelanocortin (POMC), dopamine, and gonadotropin-releasing hormone (GnRH) neurons. The ARC is crucial for appetite regulation, glucose metabolism, reproductive function, energy balance, etc., making these neurons invaluable for studying metabolic disorders such as type-2 diabetes (T2D) and obesity, as a human model for reproductive neuroendocrinology research, and for drug target discovery and high-throughput screening. Our experiments involved a range of multi-omics assays for detailed molecular, cellular, and functional characterization. We identified genes associated with T2D and obesity expressed in these neurons, along with potential candidate gene-enhancer regions. Additionally, these neurons were responsive to glucose, insulin, kisspeptin, and GLP1R agonist drugs used in diabetes and obesity treatments. This scalable platform, developed at National Center for Advancing Translational Sciences (NCATS), will be valuable in upcoming cross-institutional collaborations to study the genetics of metabolic disorders as part of the Hypothalamus Consortium in collaboration with esteemed colleagues, including Claudia A. Doege's lab at Columbia University, Francis Collins’ lab at National Human Genome Research Institute (NHGRI), and Shuibing Chen’s lab at Cornell University. A huge thank you to all the authors for their invaluable contributions! Check out our preprint for more details! https://lnkd.in/e8C-vmdJ #StemCells #Hypothalamus #TranslationalResearch #T2D #Obesity #MetabolicDisorders #ReproductiveHealth

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare genetic #epilepsy. A theme of cell biology is redundancy: if a gene or protein is lost, there are often alternate pathways that can somewhat compensate, but the compensation is seldom 100%. Researchers found that the protein EB2, a key target of CDKL5, is also phosphorylated by another protein called CDKL2. The idea is to exploit this pathway redundancy by searching for ways to boost CDKL2 levels, hoping to sufficiently activate EB2 in the absence of CDKL5. This strategy of activating or enhancing an alternate biological pathway has led to breakthroughs in other genetic diseases, such as spinal muscular atrophy with nusinersen (Spinraza). We hope this strategy pays off in CDD and leads to treatments for other genetic epilepsies and diseases! +++ 🗨️ Want to chat more about #epilepsy and #rareDisease? Book a discovery call at www.quillscience.com 🔬

Rare Disease Day is only 2 more days to go! Let's ensure that awareness continues to soar!  🌟 We are thrilled to invite you to session 2 of the Rare Disease Awareness Workshop Webinar where we are honored to have four influential academic researchers as speakers. Join us as we delve into the edge-cutting work of Dr. Don Cleveland, Dr. Tim Yu, Dr. Gene Yeo, and Dr. Jeanne Loring to understand the crucial role of iPSC-derived CNS models and ASOs in therapy development. Why you shouldn’t miss out:  1️⃣ Explore case studies on the treatment of neurodegenerative disease through neurons from stem cells;  2️⃣ Gain insights into the progress and challenges in the journey of personalized therapy;  3️⃣ Discover the immense potential of DNA and RNA for therapeutics. With expert insights and impressive case studies, this is the one not to miss! Check out the webinar now: https://lnkd.in/gSWCxP_W #RareDisease #Innovation #Webinar #Healthcare #Leadership #iXCells #DrugDevelopment #PersonalizedMedicine #StemCellsResearch #RegenerativeMedicine #Biotech #RareDiseaseAwareness #ASODevelopment #Neuroscience #CNSDiseases #PatientFocusedTherapy #RareDiseaseDay 

Exciting new research uncovers high-confidence ASD-associated genes in human iPSC-derived excitatory neurons. The network reveals novel interactions, enriched genetic/transcriptional perturbations in ASD individuals, and offers insights into neuron-specific biology related to ASDs. This study enables hypothesis generation around individual ASD-associated genes as well as identifies convergent pathways for potential therapeutic interventions or clinical stratification strategies. Dive into the study here: https://lnkd.in/ehFpEUGe.

𝐂𝐇𝐀𝐍𝐆𝐈𝐍𝐆 𝐓𝐇𝐄 𝐖𝐀𝐘 𝐖𝐄 𝐓𝐇𝐈𝐍𝐊 𝐀𝐁𝐎𝐔𝐓 𝐂𝐀𝐍𝐂𝐄𝐑 The vision of 𝐂𝐨𝐧𝐫𝐚𝐝 𝐖𝐚𝐝𝐝𝐢𝐧𝐠𝐭𝐨𝐧 laid the groundwork for 𝐃𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭𝐚𝐥 𝐁𝐢𝐨𝐥𝐨𝐠𝐲 & 𝐄𝐩𝐢𝐠𝐞𝐧𝐞𝐭𝐢𝐜𝐬. He imagined—or rather, knew—that a cell is embedded in a specific frame, the so-called "𝐓𝐡𝐞 𝐄𝐩𝐢𝐠𝐞𝐧𝐞𝐭𝐢𝐜 𝐋𝐚𝐧𝐝𝐬𝐜𝐚𝐩𝐞". His metaphor involved "𝐜𝐞𝐥𝐥𝐬 𝐝𝐞𝐩𝐢𝐜𝐭𝐞𝐝 𝐚𝐬 𝐛𝐚𝐥𝐥𝐬 𝐫𝐨𝐥𝐥𝐢𝐧𝐠 𝐝𝐨𝐰𝐧𝐡𝐢𝐥𝐥 𝐚𝐜𝐫𝐨𝐬𝐬 𝐚 𝐥𝐚𝐧𝐝𝐬𝐜𝐚𝐩𝐞 𝐨𝐟 𝐛𝐢𝐟𝐮𝐫𝐜𝐚𝐭𝐢𝐧𝐠 𝐯𝐚𝐥𝐥𝐞𝐲𝐬," which he conjured up in his mind. That's beautiful, isn't it? Each cell must follow its predefined programs—beginning with the very first stage of development. By doing this, specific "precursor cells" develop into neurons while others help to construct your muscles, heart, bones, etc. This is why Scientists are interested in learning more about the destiny of cells. Once a developmental path is known—it is possible to determine why a cell doesn't take the right one during disease. This set of epigenetic guidelines applies to all disorders—including cancer. The cancer biology field is currently focusing on the concept of the "𝐓𝐡𝐞 𝐄𝐩𝐢𝐠𝐞𝐧𝐞𝐭𝐢𝐜 𝐋𝐚𝐧𝐝𝐬𝐜𝐚𝐩𝐞" to comprehend the relationship between 𝐠𝐞𝐧𝐞𝐭𝐢𝐜 & 𝐞𝐧𝐯𝐢𝐫𝐨𝐧𝐦𝐞𝐧𝐭𝐚𝐥 𝐟𝐚𝐜𝐭𝐨𝐫𝐬 that contribute to 𝐭𝐡𝐞 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 𝐨𝐟 𝐜𝐚𝐧𝐜𝐞𝐫. ~~~ Thank you so much for reading. Wish to learn more? Hit the "𝐅𝐨𝐥𝐥𝐨𝐰"—you'll never miss out on the latest 𝐄𝐩𝐢𝐠𝐞𝐧𝐞𝐭𝐢𝐜 news! [Let your friends know too by resharing this Epi-content] "𝐘𝐨𝐮𝐫 𝐄𝐩𝐢𝐠𝐞𝐧𝐨𝐦𝐞𝐬 𝐬𝐡𝐚𝐩𝐞 𝐭𝐡𝐞 𝐝𝐞𝐬𝐭𝐢𝐧𝐲 𝐨𝐟 𝐲𝐨𝐮𝐫 𝐡𝐞𝐚𝐥𝐭𝐡" Remember that. I talk about: #precisionmedicine #epigenetics #genomics #singlecell #genetics #science #health #omics — Always be on top of your DNA!

Pengfei Liu, PhD, FACMGG, is discussing everything RNA-seq in next week's journal club! Don't miss his live presentation delving into the specifics on this innovative rare disease diagnostic workflow. During Dr. Liu's presentation he'll tackle: 🧬How transcriptome RNA-seq using accessible tissues can fall short in characterizing genes involved in neurological disorders. 💡How cell transdifferentiation is streamlined into a diagnostic RNA-seq workflow. 🥼How to increase molecular diagnostic yield by activating neurological disease-associated genes and neuron-specific isoforms with induced neuron RNA-seq. Gain these insights on June 12 by registering today: https://lnkd.in/eeH-XUHJ #ASHG #HumanGenetics

"Investigators reveal how genetic changes in certain types of brain cells may contribute to the inflammatory response seen in Alzheimer's disease." A new study by investigators Vicky Chou, Richard V. Pearse II, Tracy L. Young-Pearse, et al. "explores how the genetics of #Microglia contribute to #Neuroinflammation and, in turn, #AlzheimersDisease." "The team revealed that a reduction of INPP5D, a gene found in microglia, results in neuroinflammation and increases the risk for #Alzheimers. Their results have important implications for the design of microglia-centered therapeutics for Alzheimer's disease and related disorders." Learn More in Nature Communications | Nature Portfolio https://lnkd.in/gYgYPyaY INPP5D regulates inflammasome activation in human microglia - Vicky Chou, Richard V. Pearse II, David A. Bennett, Philip De Jager, Vilas Menon, Tracy Young-Pearse, et al. Brigham and Women's Hospital and Harvard Medical School Columbia University Irving Medical Center Emory University School of Medicine Rush Alzheimer’s Disease Center, RUSH University Medical Center Harvard Stem Cell Institute, Harvard University