A5091065467- Cancer Genomics and Diagnostics
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Molecular Biology Techniques and Applications
- Ferroptosis and cancer prognosis
- Heat shock proteins research
- RNA Research and Splicing
- Nuclear Structure and Function
- interferon and immune responses
- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
- Prion Diseases and Protein Misfolding
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Cancer-related Molecular Pathways
- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- Effects and risks of endocrine disrupting chemicals
- Immune Cell Function and Interaction
- Genomics and Phylogenetic Studies
- Cancer, Lipids, and Metabolism
- RNA and protein synthesis mechanisms
- 3D Printing in Biomedical Research
Medical University of Vienna
2023-2025
Comprehensive Cancer Center Vienna
2023-2024
Center for Cancer Research
2023-2024
University of California, San Francisco
2018-2023
University of California San Francisco Medical Center
2022
City College of San Francisco
2022
UCSF Helen Diller Family Comprehensive Cancer Center
2018-2021
Heidelberg University
2010-2016
University Hospital Heidelberg
2014-2016
DKFZ-ZMBH Alliance
2010-2015
Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing biology and enabling new insights into the physiology human organs. We created a reference atlas comprising nearly 500,000 cells from 24 different tissues organs, many same donor. This enabled molecular more than 400 types, their distribution across tissues, tissue-specific variation in gene expression. Using multiple single donor identification clonal T between mutation rate B cells,...
Hsp100 and Hsp70 chaperones in bacteria, yeast, plants cooperate to reactivate aggregated proteins. Disaggregation relies on function ATP-dependent threading of polypeptides through the pore AAA(+) hexamer. In both also promote propagation prions by fibril fragmentation, but their functional interplay is controversial. Here, we demonstrate that were essential for species-specific targeting partner ClpB Hsp104, respectively, heat-induced protein aggregates vivo. inactivation yeast abrogated...
Abstract Cell-free RNA from liquid biopsies can be analyzed to determine disease tissue of origin. We extend this concept identify cell types origin using the Tabula Sapiens transcriptomic atlas as well individual atlases in combination with Human Protein Atlas consensus dataset. define type signature scores, which allow inference that contribute cell-free for a variety diseases.
Abstract The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results comparative lower tract transcriptional profiling tracheal aspirate 52 critically ill patients with COVID-19 or etiologies, as well controls without ARDS. In contrast to a “cytokine storm,” observe reduced proinflammatory gene expression in when compared due causes. is characterized by...
SignificanceBisphenol A (BPA), found in many plastic products, has weak estrogenic effects that can be harmful to human health. Thus, structurally related replacements-bisphenol S (BPS) and bisphenol F (BPF)-are coming into wider use with very few data about their biological activities. Here, we compared the of BPA, BPS, BPF on mammary organoids established from normal breast tissue. BPS disrupted organoid architecture induced supernumerary branching. At a proteomic level, bisphenols altered...
Abstract Few patients with triple negative breast cancer (TNBC) benefit from immune checkpoint inhibitors complete and durable remissions being quite rare. Oncogenes can regulate tumor infiltration, however whether oncogenes dictate diminished response to immunotherapy these effects are reversible remains poorly understood. Here, we report that TNBCs elevated MYC expression resistant inhibitor therapy. Using mouse models patient data, show signaling is associated low cell PD-L1, overall...
Abstract Cancer cells often co-opt post-transcriptional regulatory mechanisms to achieve pathologic expression of gene networks that drive metastasis. Translational control is a major hub in oncogenesis; however, its effects on cancer progression remain poorly understood. Here, address this, we used ribosome profiling compare genome-wide translation efficiencies and highly metastatic breast patient-derived xenografts. We developed dedicated regression-based methods analyse alternative...
Genomic and proteomic screens have identified numerous host factors of SARS-CoV-2, but efficient delineation their molecular roles during infection remains a challenge. Here we use Perturb-seq, combining genetic perturbations with single-cell readout, to investigate how inactivation changes the course SARS-CoV-2 response in human lung epithelial cells. Our high-dimensional data resolve complex phenotypes such as shifts stages modulations interferon response. However, only small percentage...
Abstract Background Members of the karyopherin superfamily serve as nuclear transport receptors/adaptor proteins and provide exchange macromolecules between nucleo- cytoplasm. Emerging evidence suggests a subset karyopherins to be dysregulated in hepatocarcinogenesis including karyopherin-α2 (KPNA2). However, functional regulatory role KPNA2 liver cancer remains incompletely understood. Methods Quantitative proteomics (LC-MS/MS, ~ 1750 total) was used study changes global protein abundance...
Abstract Immunity suffers a function deficit during aging, and the incidence of cancer is increased in elderly. However, most models employ young mice, which are poorly representative adult patients. We have previously reported that Triple-Therapy (TT), involving antigen-presenting-cell activation by vinorelbine generation TCF1 + -stem-cell-like T cells (scTs) cyclophosphamide significantly improved anti-PD-1 efficacy anti-PD1-resistant like Triple-Negative Breast Cancer (TNBC) Non-Hodgkin’s...
Abstract Immunity declines with age, leading to functional deficits and an increased incidence of cancer in the elderly. Despite this, most models utilize young (6-8 week old) mice, which are not representative adult patients. Triple negative breast (TNBC) typically occurs around 30-50 years can be approximated 12 months mice. We previously demonstrated that a Triple-Therapy (TT) including APC activation via vinorelbine generation TCF1+ stem-cell-like T cells (scTs) by cyclophosphamide...
Summary It is still an open question how intracellular cytoskeleton directs the synthesis of peptidoglycan exoskeleton. In contrast to MreB rod‐shaped bacteria, which essential for lateral cell wall synthesis, Streptomyces coelicolor has a role in sporulation. To study function S. mre gene cluster consisting mreB, mreC, mreD, pbp2 and sfr , we generated non‐polar replacement mutants. The individual mutants were viable growth substrate mycelium was not affected. However, all produced enlarged...
Yeast prions constitute a “protein-only” mechanism of inheritance that is widely deployed by wild yeast to create diverse phenotypes. One the best-characterized prions, [ PSI + ], governed conformational change in prion domain Sup35, translation-termination factor. When this switches from its normal soluble form an insoluble amyloid, ensuing protein synthesis creates new traits. Two factors make these traits heritable: ( i ) amyloid conformation self-templating; and ii protein-remodeling...
Proteins of the karyopherin superfamily including importins and exportins represent an essential part nucleocytoplasmic transport machinery. However, functional relevance regulation karyopherins in hepatocellular carcinoma (HCC) is poorly understood. Here we identified cellular apoptosis susceptibility (CAS, exportin-2) its substrate importin-α1 (imp-α1) among significantly up-regulated factor genes HCC. Disruption CAS/imp-α1 cycle by RNA i HCC cell lines resulted decreased tumor growth...
Metastasis is the leading cause of cancer-related deaths. It unclear how intratumor heterogeneity (ITH) contributes to metastasis and metastatic cells adapt distant tissue environments. The study these adaptations challenged by limited access patient material a lack experimental models that appropriately recapitulate ITH. To investigate cell contribution ITH metastasis, we analyzed single-cell transcriptomes matched primary tumors metastases from patient-derived xenograft breast cancer. We...
About 40% of clear-cell renal cell carcinomas (ccRCC) harbour mutations in Polybromo-1 (PBRM1), encoding the BAF180 subunit a SWI/SNF chromatin remodelling complex. This qualifies PBRM1 as major cancer gene ccRCC. The protein alters structure and its known functions include transcriptional regulation by controlling accessibility DNA influencing p53 activity. Since little is about PBRM1, we studied possible mechanisms interaction partners involved expression. Activation RCC cells resulted...
// Juliane Winkler 1 , Stephanie Roessler Carsten Sticht 2 Amanda L. DiGuilio 3 Elisabeth Drucker Kerstin Holzer Eva Eiteneuer Esther Herpel 1, 4 Kai Breuhahn Norbert Gretz Peter Schirmacher Alessandro Ori 5, 6 Stephan Singer 5 Institute of Pathology, University Hospital Heidelberg, Germany Medical Research Centre, Faculty Mannheim, Department Chemistry, Chemical Biology and Biomedical Engineering, Stevens Technology, Hoboken, NJ, USA Tissue Bank the National Center for Tumor Diseases (NCT)...
ABSTRACT We describe MULTI-seq: A rapid, modular, and universal scRNA-seq sample m ultiplexing strategy u sing l ipid- t agged i ndices. MULTI-seq reagents can barcode any cell type from species with an accessible plasma membrane. The method is compatible enzymatic tissue dissociation, also preserves viability endogenous gene expression patterns. leverage these features to multiplex the analysis of multiple solid tissues comprising human mouse cells isolated patient-derived xenograft models....