Michaela Willi
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View article: Patients’, parents’, and survivors’ perspective about AI applications in pediatric oncology
Patients’, parents’, and survivors’ perspective about AI applications in pediatric oncology Open
Patients, parents and survivors of childhood cancer are those who represent the critical link between the clinical and technical research spheres. Thus, UNICA4EU worked towards a patient- centric approach to integrate AI in the care pathwa…
View article: Cell-specific and shared regulatory elements control a multigene locus active in mammary and salivary glands
Cell-specific and shared regulatory elements control a multigene locus active in mammary and salivary glands Open
Regulation of high-density loci harboring genes with different cell-specificities remains a puzzle. Here we investigate a locus that evolved through gene duplication and contains eight genes and 20 candidate regulatory elements, including …
View article: Indian Hedgehog release from TNF-activated renal epithelia drives local and remote organ fibrosis
Indian Hedgehog release from TNF-activated renal epithelia drives local and remote organ fibrosis Open
Progressive fibrosis is a feature of aging and chronic tissue injury in multiple organs, including the kidney and heart. Glioma-associated oncogene 1 expressing (Gli1 + ) cells are a major source of activated fibroblasts in multiple organs…
View article: Cell-specific and shared enhancers control a high-density multi-gene locus active in mammary and salivary glands
Cell-specific and shared enhancers control a high-density multi-gene locus active in mammary and salivary glands Open
Regulation of high-density loci harboring genes with different cell-specificities remains a puzzle. Here we investigate a locus that evolved through gene duplication 1 and contains eight genes and 20 candidate regulatory elements, includin…
View article: Testing methods to diagnose TRK fusion cancer - a plain language summary and patient perspective
Testing methods to diagnose TRK fusion cancer - a plain language summary and patient perspective Open
The results of this study provide a guidance for healthcare professionals on the methods used for testing to identify patients that have TRK fusion cancer. By characterizing the types of testing done across cancer types, patients and their…
View article: Indian Hedgehog release from renal epithelia drives local and remote organ fibrosis
Indian Hedgehog release from renal epithelia drives local and remote organ fibrosis Open
Chronic kidney disease (CKD) and ageing inhibit tissue regeneration and increase risks of organ fibrosis and cardiovascular disease. Increased numbers of leukocytes are present in the circulation and within the kidney of ageing individuals…
View article: Redundant and non-redundant cytokine-activated enhancers control Csn1s2b expression in the lactating mouse mammary gland
Redundant and non-redundant cytokine-activated enhancers control Csn1s2b expression in the lactating mouse mammary gland Open
Enhancers are transcription factor platforms that synergize with promoters to control gene expression. Here, we investigate enhancers that activate gene expression several hundred-fold exclusively in the lactating mouse mammary gland. Usin…
View article: Enhancer and super-enhancer dynamics in repair after ischemic acute kidney injury
Enhancer and super-enhancer dynamics in repair after ischemic acute kidney injury Open
The endogenous repair process can result in recovery after acute kidney injury (AKI) with adaptive proliferation of tubular epithelial cells, but repair can also lead to fibrosis and progressive kidney disease. There is currently limited k…
View article: P0511ENHANCER AND SUPER-ENHANCER DYNAMICS IN REPAIR AFTER ISCHEMIC ACUTE KIDNEY INJURY
P0511ENHANCER AND SUPER-ENHANCER DYNAMICS IN REPAIR AFTER ISCHEMIC ACUTE KIDNEY INJURY Open
Background and Aims The endogenous repair process of the mammalian kidney allows rapid recovery after acute kidney injury (AKI) through robust proliferation of tubular epithelial cells. There is currently limited understanding of which tra…
View article: Cytosine base editor 4 but not adenine base editor generates off-target mutations in mouse embryos
Cytosine base editor 4 but not adenine base editor generates off-target mutations in mouse embryos Open
Deaminase base editing has emerged as a tool to install or correct point mutations in the genomes of living cells in a wide range of organisms. However, the genome-wide off-target effects introduced by base editors in the mammalian genome …
View article: Cytosine but not adenine base editor generates mutations in mice
Cytosine but not adenine base editor generates mutations in mice Open
Deaminase base editing has emerged as a tool to install or correct point mutations in the genomes of living cells in a wide range of organisms and its ultimate success therapeutically depends on its accuracy. Here we have investigated the …
View article: Progressing super-enhancer landscape during mammary differentiation controls tissue-specific gene regulation
Progressing super-enhancer landscape during mammary differentiation controls tissue-specific gene regulation Open
The mammary luminal lineage relies on the common cytokine-sensing transcription factor STAT5 to establish super-enhancers during pregnancy and initiate a genetic program that activates milk production. As pups grow, the greatly increasing …
View article: Assessing eRNAs associated with a cytokine-sensing mammary super-enhancer
Assessing eRNAs associated with a cytokine-sensing mammary super-enhancer Open
Enhancers are transcription factor platforms that also bind RNA polymerase II and generate enhancer RNAs (eRNA). Although eRNAs have been suggested as predictors of enhancer activities and possibly key components facilitating transcription…
View article: Functional assessment of CTCF sites at cytokine-sensing mammary enhancers using CRISPR/Cas9 gene editing in mice
Functional assessment of CTCF sites at cytokine-sensing mammary enhancers using CRISPR/Cas9 gene editing in mice Open
The zinc finger protein CTCF has been invoked in establishing boundaries between genes, thereby controlling spatial and temporal enhancer activities. However, there is limited genetic evidence to support the concept that these boundaries r…
View article: dbVar structural variant cluster set for data analysis and variant comparison
dbVar structural variant cluster set for data analysis and variant comparison Open
dbVar houses over 3 million submitted structural variants (SSV) from 120 human studies including copy number variations (CNV), insertions, deletions, inversions, translocations, and complex chromosomal rearrangements. Users can submit mult…
View article: Lineage-Specific and Non-specific Cytokine-Sensing Genes Respond Differentially to the Master Regulator STAT5
Lineage-Specific and Non-specific Cytokine-Sensing Genes Respond Differentially to the Master Regulator STAT5 Open
STAT5, a member of the family of signal transducers and activators of transcription, senses cytokines and controls the biology of cell lineages, including mammary, liver, and T cells. Here, we show that STAT5 activates lineage-specific and…
View article: Differential cytokine sensitivities of STAT5-dependent enhancers rely on<i>Stat5</i>autoregulation
Differential cytokine sensitivities of STAT5-dependent enhancers rely on<i>Stat5</i>autoregulation Open
Cytokines utilize the transcription factor STAT5 to control cell-specific genes at a larger scale than universal genes, with a mechanistic explanation yet to be supplied. Genome-wide studies have identified putative STAT5-based mammary-spe…
View article: Loss of CHD1 causes decreased species diversity in the gut microbiome.
Loss of CHD1 causes decreased species diversity in the gut microbiome. Open
(A) Relative abundance of bacterial families (97% similarity threshold) determined by 16S rDNA sequencing in Chd1WT/WT and Chd1-/- samples. Families present at levels less than 1.5% were summarized as “others“. (B) Heatmap of the 25 most a…
View article: Age-related changes of bacterial load and species distribution in <i>Chd1</i> mutant and wild-type flies.
Age-related changes of bacterial load and species distribution in <i>Chd1</i> mutant and wild-type flies. Open
(A) Flies of the indicated ages were surface-sterilized and homogenates were plated on Ace agar (left panel) to select for Acetobacteraceae or on MRS agar (right panel) to select for Lactobacillaceae. CFUs per fly were calculated and mean …
View article: Time-dependent decrease in supplemented <i>L</i>. <i>plantarum</i> in <i>Chd1</i><sup><i>-/-</i></sup> but not <i>Chd1</i><sup><i>WT/WT</i></sup> flies.
Time-dependent decrease in supplemented <i>L</i>. <i>plantarum</i> in <i>Chd1</i><sup><i>-/-</i></sup> but not <i>Chd1</i><sup><i>WT/WT</i></sup> flies. Open
Flies were fed on L. plantarum overnight, transferred to fresh food vials and collected at the indicated days after inoculation. (A) Lactobacillus load was determined by plating fly homogenates on MRS agar; (B) L. plantarum was detected by…
View article: The microbiome composition in the gut of <i>Chd1</i><sup><i>-/-</i></sup> and <i>Chd1</i><sup><i>WT/WT</i></sup> flies is significantly different.
The microbiome composition in the gut of <i>Chd1</i><sup><i>-/-</i></sup> and <i>Chd1</i><sup><i>WT/WT</i></sup> flies is significantly different. Open
(A) Principal Coordinate Analysis (PCoA) plot depicting β-diversity by jackknifed UniFrac distances (normalized, weighted UniFrac metric) based on 97% similarity OTU assignments. Chd1WT/WT and Chd1-/- replicates differ considerably for PC1…
View article: Impact of the Chromatin Remodeling Factor CHD1 on Gut Microbiome Composition of Drosophila melanogaster
Impact of the Chromatin Remodeling Factor CHD1 on Gut Microbiome Composition of Drosophila melanogaster Open
The composition of the intestinal microbiota of Drosophila has been studied in some detail in recent years. Environmental, developmental and host-specific genetic factors influence microbiome composition in the fly. Our previous work has i…