Sarah Kim-Hellmuth
A5039696630- Genetic Associations and Epidemiology
- RNA Research and Splicing
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Immune Cell Function and Interaction
- Bioinformatics and Genomic Networks
- Genetic Mapping and Diversity in Plants and Animals
- Immune Response and Inflammation
- Cancer-related molecular mechanisms research
- Gene expression and cancer classification
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- Peroxisome Proliferator-Activated Receptors
- Genomics and Chromatin Dynamics
- interferon and immune responses
- Inflammasome and immune disorders
- Metabolism, Diabetes, and Cancer
- RNA Interference and Gene Delivery
- Immune cells in cancer
- Molecular Biology Techniques and Applications
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Digital Rights Management and Security
- Telomeres, Telomerase, and Senescence
- Genetics, Aging, and Longevity in Model Organisms
Ludwig-Maximilians-Universität München
2006-2025
Helmholtz Zentrum München
2023-2025
LMU Klinikum
2021-2025
Virginia Commonwealth University
2018-2025
New York Genome Center
2016-2024
University of California, Los Angeles
2000-2024
Chonnam National University Hospital
2024
German Center for Pediatric and Adolescent Rheumatology
2024
Emory University
2020-2023
Columbia University
2016-2022
The Genotype-Tissue Expression (GTEx) project dissects how genetic variation affects gene expression and splicing.
The structural basis for the distinction of viral RNA from abundant self in cytoplasm virally infected cells is largely unknown. We demonstrated that 5'-triphosphate end generated by polymerases responsible retinoic acid-inducible protein I (RIG-I)-mediated detection molecules. Detection abrogated capping or nucleoside modification RNA, both occurring during posttranscriptional processing eukaryotes. Genomic prepared a negative-strand virus and virus-infected (but not noninfected cells)...
Abstract Scalable, integrative methods to understand mechanisms that link genetic variants with phenotypes are needed. Here we derive a mathematical expression compute PrediXcan (a gene mapping approach) results using summary data (S-PrediXcan) and show its accuracy general robustness misspecified reference sets. We apply this framework 44 GTEx tissues 100+ from GWAS meta-analysis studies, creating growing public catalog of associations seeks capture the effects variation on human...
Fast and reliable detection of patients with severe heterogeneous illnesses is a major goal precision medicine1,2. Patients leukaemia can be identified using machine learning on the basis their blood transcriptomes3. However, there an increasing divide between what technically possible allowed, because privacy legislation4,5. Here, to facilitate integration any medical data from owner worldwide without violating laws, we introduce Swarm Learning-a decentralized machine-learning approach that...
Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex in gene expression and genetic regulation across 44 tissue sources surveyed by Genotype-Tissue Expression project (GTEx, v8 release). demonstrate that influences levels cellular composition samples body. A total 37% all genes sex-biased at least one tissue. identify cis quantitative trait loci (eQTLs)...
Cell type composition, estimated from bulk tissue, maps the cellular specificity of genetic variants.
Telomere length within an individual varies in a correlated manner across most tissues.
The resources generated by the GTEx consortium offer unprecedented opportunities to advance our understanding of biology human diseases. Here, we present an in-depth examination phenotypic consequences transcriptome regulation and a blueprint for functional interpretation genome-wide association study-discovered loci. Across broad set complex traits diseases, demonstrate widespread dose-dependent effects RNA expression splicing. We develop data-driven framework benchmark methods that...
Abstract The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues, and link these regulatory mechanisms trait disease associations. Here, we present analyses of v8 data, based 17,382 RNA-sequencing samples from 54 tissues 948 post-mortem donors. We comprehensively associations for gene expression splicing in cis trans , showing that are found almost all genes, describe underlying molecular their contribution...
The immune system plays a major role in human health and disease, understanding genetic causes of interindividual variability responses is vital. Here, we isolate monocytes from 134 genotyped individuals, stimulate these cells with three defined microbe-associated molecular patterns (LPS, MDP, 5'-ppp-dsRNA), profile the transcriptomes at time points. Mapping expression quantitative trait loci (eQTL), identify 417 response eQTLs (reQTLs) varying effects between conditions. We characterize...
Abstract The inflammasome pathway functions to regulate caspase‐1 activation in response a broad range of stimuli. Caspase‐1 is required for the maturation pivotal pro‐inflammatory cytokines pro‐IL‐1β family. In addition, leads certain type cell death known as pyroptosis. Activation has been shown play critical role recognition and containment various microbial pathogens, including intracellularly replicating Listeria monocytogenes ; however, pathways activated during L. infection are only...
Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear superfamily that activated by binding certain fatty acids, eicosanoids, and insulin-sensitizing thiazolidinediones (TZD). The TZD troglitazone (TRO) inhibits vascular smooth muscle cell proliferation migration both <i>in vitro</i> vivo</i>. precise mechanism its antiproliferative activity, however, has not been elucidated. We report here PPARγ ligands inhibit rat aortic blocking events critical for G<sub>1</sub>...
Novel strategies for the therapy of recurrent ovarian cancer are warranted. We report a study combinatorial approach encompassing dendritic cell (DC)-based autologous whole tumor vaccination and anti-angiogenesis therapy, followed by adoptive transfer vaccine-primed CD3/CD28-co-stimulated lymphocytes. Recurrent patients whom lysate was available from prior cytoreductive surgery underwent conditioning with intravenous bevacizumab oral metronomic cyclophosphamide, sequentially (1) plus DCs...
Outliers in the human transcriptome reveal functional effects of rare genetic variants.
Abstract Allele expression (AE) analysis robustly measures cis -regulatory effects. Here, we present and demonstrate the utility of a vast AE resource generated from GTEx v8 release, containing 15,253 samples spanning 54 human tissues for total 431 million measurements at SNP level 153 haplotype level. In addition, develop an extension our tool phASER that allows effect sizes variants to be estimated using haplotype-level data. This is largest date, are able make data publicly available. We...
Detection of non-self RNA by TLRs within endosomes and retinoic acid-inducible gene I (RIG-I)-like helicases in the cytosol is central to mammalian antiviral immunity. In this study, we used pathway-specific agonists targeted delivery address immunorecognition primary human immune cells. Within PBMC, plasmacytoid dendritic cells (pDC) monocytes were found be responsible for IFN-alpha production upon RNA. The mechanisms recognition pDC distinct. pDC, ssRNA dsRNA oligonucleotides was...
Abstract Toll-like receptors (TLRs) play a key role in innate immunity. Apart from their function host defense, dysregulation TLR signalling can confer risk to autoimmune diseases, septic shock or cancer. Here we report genetic variants and transcripts that are active only during contribute interindividual differences immune response. Comparing unstimulated versus TLR4-stimulated monocytes reveals 1,471 expression quantitative trait loci (eQTLs) unique TLR4 stimulation. Among these find...