Matthew T Weirauch

Oct 29, 2024 | nature.com | Matthew T Weirauch

AbstractMultinucleated skeletal muscle cells need to acquire additional nuclei through fusion with activated skeletal muscle stem cells when responding to both developmental and adaptive growth stimuli. A fundamental question in skeletal muscle biology has been the reason underlying this need for new nuclei in cells that already harbor hundreds of nuclei.

Aug 9, 2024 | nature.com | Qiang Wang |taehyeung Kim |Marta Martínez-Bonet |Sangwan Sim |Jing Cui |Jeffrey A Sparks | +9 more

Genome-wide association studies implicate multiple loci in risk for systemic lupus erythematosus (SLE), but few contain exonic variants, rendering systematic identification of non-coding variants essential to decoding SLE genetics. We utilized SNP-seq and bioinformatic enrichment to interrogate 2180 single-nucleotide polymorphisms (SNPs) from 87 SLE risk loci for potential binding of transcription factors and related proteins from B cells. 52 SNPs that passed initial screening were tested by electrophoretic mobility shift and luciferase reporter assays. To validate the approach, we studied rs2297550 in detail, finding that the risk allele enhanced binding to the transcription factor Ikaros (encoded by IKZF1), thereby modulating expression of IKBKE. Correspondingly, primary cells from genotyped healthy donors bearing the risk allele expressed higher levels of the interferon / NF-κB regulator IKKε. Together, these findings define a set of likely functional non-coding lupus risk variants and identify a regulatory pathway involving rs2297550, Ikaros, and IKKε implicated by human genetics in risk for SLE. Here, the authors use SNP-seq to screen 87 lupus risk loci for functional non-coding variants. Validation at one locus identified a risk variant through which enhanced Ikaros binding amplifies expression of the interferon / NFκB regulator IKKε.

Jan 26, 2024 | scienceblog.cincinnatichildrens.org | Leah C. Kottyan |Matthew T Weirauch |Marc E. Rothenberg

Symptoms of eosinophilic esophagitis (EoE) mirror those of many common conditions, making it challenging to diagnose. Surgical biopsy is the diagnostic gold standard, but no guidelines exist to help clinicians decide whether to perform one. Researchers at Cincinnati Children’s hope to improve the way genetic risk can be incorporated into decision making with help from a novel, DNA-based tool called massively parallel reporter assays (MPRA).