Zachary Welch’s Post

Tissue-specific gene regulation by diabetes-linked transcription factors Scientists have generated a comprehensive map of the gene targets regulated by the transcription factors HNF4A and HNF1A in human pancreatic beta cells and liver cells. Published in the journal Nature Communications, the study revealed common and tissue-specific molecular pathways regulated by HNF4A and HNF1A, two proteins that possess important functions governing the development and function of the pancreas and liver. Notably, the scientists identified several novel gene targets in pancreatic beta cells, the cells responsible for insulin production, that may play previously unknown roles in regulating insulin secretion. As genetic variants in HNF4A and HNF1A are known to cause a rare form of diabetes called Maturity Onset Diabetes of the Young (MODY) and also influence risk for the more common type 2 diabetes, these findings provide valuable insights into potential therapeutic targets for diabetes. #ScienceMission #sciencenewshighlights https://lnkd.in/gAG9qRsX

Congenital central hypoventilation syndrome (#CCHS) is a rare genetic disease resulting from in-frame triplet duplications in the paired-like homeobox 2B (PHOX2B) gene, leading to an expansion of the normal #polyalanine (polyAla) stretch from 20 residues to +4 to +13 additional alanine residues. Read our commentary on the exciting research by Africano et al. to find a cure for CCHS: https://lnkd.in/dRbRGZWR and the full paper by Africano et al. in published Molecular Therapy Nucleic Acids: https://lnkd.in/dmFaTEYf

💥 New Publication Alert 💡 Title: Association of TGFBR2 gene polymorphisms (rs6785358 and rs764522) with congenital heart disease susceptibility in Egyptians 🌟 Conclusions: These findings indicate that TGFBR2 gene SNPs (rs6785358 and rs764522) may be risk factors for CHD in Egyptians. 🧐 Authors: Nahed Dawood, El-Shaimaa Shabana, Ashraf A.H. El-Midany, Faten R. Abdelghaffar, Islam El-Garawani, Rizk Elbaz 🔏 Keywords: Transforming growth factor beta receptor II (#TGFBR2) single nucleotide polymorphisms (#SNP) congenital #heartdisease case-control study Curious to know more? Dive into the article: ➡ https://lnkd.in/gPf7pMf6

Mitochondrial perturbation in the intestine causes microbiota-dependent injury and gene signatures discriminative of inflammatory disease; Elisabeth Urbauer, et al.; Cell Host and Microbe: August 14, 2024; Open access: https://lnkd.in/eQxyeZ8X

🚀 Excited to share my latest research paper: "CDK9 phosphorylates RUNX1 to promote megakaryocytic fate in megakaryocytic-erythroid progenitors" In this study, we explore the crucial role of RUNX1 in the specification of megakaryocytic and erythroid lineages from primary human megakaryocytic-erythroid progenitors (MEPs). Our findings reveal that RUNX1 is a key modulator of gene expression during MEP fate specification. Overexpression of RUNX1 promotes megakaryocyte (Mk) specification, while its inhibition favors erythroid (E) lineage commitment. Notably, we identify cyclin-dependent kinase 9 (CDK9) as a novel regulator, where its inhibition leads to decreased RUNX1 phosphorylation and increased E commitment. This highlights the intricate interplay between RUNX1 phosphorylation and lineage specification. Read the full paper here 👉 https://lnkd.in/eX_4bQHy

Bacterial Antiviral Mechanism Triggers Growth Arrest through de novo Neo Gene New work from the lab of Sam Sternberg, PhD, associate professor of biochemistry and molecular biology at Columbia University and an HHMI Investigator, describes the mechanism of antiviral immunity used by a DRT. The findings show that the DRT achieves population-level antiviral immunity via cellular growth arrest. More specifically, upon phage infection, reverse transcriptase synthesizes genes whose protein products help shut down cell growth .https://hubs.li/Q02KNRkY0

MicroRNA Breakthrough: Nobel Prize Awarded for Transformative Discovery in Gene Regulation https://lnkd.in/gtPRkQgW #NobelPrize #MicroRNA #GeneRegulation #VictorAmbros #GaryRuvkun #MolecularBiology #MedicalResearch #Biotechnology #PersonalizedMedicine #HealthInnovation #RNAResearch #CancerResearch #ScientificDiscovery #MedicalBreakthrough #Genetics #Biomarkers

It's been a long time coming and happy to share that my post-doctoral research project has finally been published in Nature Communications. The article provides a resource to the community on the gene targets of HNF4A and HNF1A, two important transcription factors that regulate gene networks involved in pancreas and liver development, using chromatin immunoprecipitation sequencing (ChIP-Seq). This work would not have been possible without the steadfast collaboration with Soumita Ghosh, the support and persistence from my PI Adrian Teo, and effort from Yaw Sing Tan to model gene variants. https://lnkd.in/gbUzrggt In this paper we uncovered an extensive list of genomic targets and pathways in various pancreatic and hepatic cell models, including several genes that were found to influence insulin secretion, the core function of pancreatic beta cells. We also discovered a new molecular mechanism that may contribute to the association between a genetic risk variant and type 2 diabetes. A single research group will not be able to exploit all the results, and we hope that this will act as a resource to the community to continue to uncover deeper mechanisms underlying pancreatic beta cell function and diabetes pathophysiology. #HNF1A #HNF4A #diabetes #betacells #insulin

Proud to be featured by the University of Helsinki to share our latest article, revealing how a mutation in the RFX6 gene significantly increases the risk of type 2 and gestational diabetes. This discovery is particularly important for Finland, where this mutation is most prevalent. #DiabetesResearch #StemCells #BetaCells #CRISPR

Metabolic gene function discovery platform GeneMAP identifies SLC25A48 as necessary for mitochondrial choline import. Organisms maintain metabolic homeostasis through the combined functions of small-molecule transporters and enzymes. While many metabolic components have been well established, a substantial number remains without identified physiological substrates. To bridge this gap, we have leveraged large-scale plasma metabolome genome-wide association studies (GWAS) to develop a multiomic Gene-Metabolite Association Prediction (GeneMAP) discovery platform. GeneMAP can generate accurate predictions and even pinpoint genes that are distant from the variants implicated by GWAS. In particular, our analysis identified solute carrier family 25 member 48 (SLC25A48) as a genetic determinant of plasma choline levels. Mechanistically, SLC25A48 loss strongly impairs mitochondrial choline import and synthesis of its downstream metabolite betaine. Integrative rare variant and polygenic score analyses in UK Biobank provide strong evidence that the SLC25A48 causal effects on human disease may in part be mediated by the effects of choline. Altogether, our study provides a discovery platform for metabolic gene function and proposes SLC25A48 as a mitochondrial choline transporter. Source: Nat Genet https://lnkd.in/gZM9z7UW