Jan‐Philipp Mallm
A5061170036- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Multiple Myeloma Research and Treatments
- Chronic Lymphocytic Leukemia Research
- Genomics and Chromatin Dynamics
- Immune Cell Function and Interaction
- Cancer-related molecular mechanisms research
- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Circular RNAs in diseases
- Hematopoietic Stem Cell Transplantation
- T-cell and B-cell Immunology
- Protein Degradation and Inhibitors
- Cancer Cells and Metastasis
- RNA modifications and cancer
- RNA Research and Splicing
- Chemokine receptors and signaling
- Mesenchymal stem cell research
- Lymphoma Diagnosis and Treatment
- Advanced biosensing and bioanalysis techniques
- Telomeres, Telomerase, and Senescence
- SARS-CoV-2 and COVID-19 Research
- Immunodeficiency and Autoimmune Disorders
German Cancer Research Center
2016-2025
Heidelberg University
2016-2025
DKFZ-ZMBH Alliance
2012-2023
Deutschen Konsortium für Translationale Krebsforschung
2020
Hopp Children's Cancer Center Heidelberg
2018-2019
European Molecular Biology Organization
2013-2015
Heidelberg University
2014
Abstract Hepatocellular carcinoma (HCC) can have viral or non-viral causes 1–5 . Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification patients optimal response to therapy unmet need 6,7 Here we report the progressive accumulation exhausted, unconventionally activated CD8 + PD1 T cells in NASH-affected livers. In preclinical models NASH-induced therapeutic immunotherapy targeted at programmed...
Abstract Fibroblasts are an essential cell population for human skin architecture and function. While fibroblast heterogeneity is well established, this phenomenon has not been analyzed systematically yet. We have used single-cell RNA sequencing to analyze the transcriptomes of more than 5,000 fibroblasts from a sun-protected area in healthy donors. Our results define four main subpopulations that can be spatially localized show differential secretory, mesenchymal pro-inflammatory functional...
The global impact of DNA methylation on alternative splicing is largely unknown. Using a genome-wide approach in wild-type and methylation-deficient embryonic stem cells, we found that can either enhance or silence exon recognition affects the more than 20% exons. These exons are characterized by distinct genetic epigenetic signatures. Alternative regulation subset these be explained heterochromatin protein 1 (HP1), which silences enhances position-dependent manner. We constructed an...
Specialized regulatory T (Treg) cells accumulate and perform homeostatic regenerative functions in nonlymphoid tissues. Whether common precursors for nonlymphoid-tissue Treg exist how they differentiate remain elusive. Using transcription factor nuclear factor, interleukin 3 regulated (Nfil3) reporter mice single-cell RNA-sequencing (scRNA-seq), we identified two precursor stages of 33 (IL-33) receptor ST2-expressing tissue cells, which resided the spleen lymph nodes. Global chromatin...
During differentiation of embryonic stem cells, chromatin reorganizes to establish cell type-specific expression programs. Here, we have dissected the linkages between DNA methylation (5mC), hydroxymethylation (5hmC), nucleosome repositioning, and binding transcription factor CTCF during this process. By integrating MNase-seq ChIP-seq experiments in mouse cells (ESC) their differentiated counterparts with biophysical modeling, found that interplay these factors depends on genomic context....
Cohesin plays an important role in chromatid cohesion and has additional functions higher-order chromatin organization transcriptional regulation. The binding of cohesin to euchromatic regions is largely mediated by CTCF or the mediator complex. However, it currently unknown how recruited pericentric heterochromatin mammalian cells. Here we define histone methyltransferase Suv4-20h2 as a major structural constituent that mediates compaction recruitment. stably associates with through...
Article24 March 2016Open Access Transparent process Environment-induced epigenetic reprogramming in genomic regulatory elements smoking mothers and their children Tobias Bauer orcid.org/0000-0002-4961-3639 Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany Search for more papers by this author Saskia Trump Department Environmental Immunology, Helmholtz Centre Leipzig - UFZ, Leipzig, Naveed Ishaque Heidelberg Personalized Oncology, DKFZ-HIPO,...
Virtually all patients with multiple myeloma become unresponsive to treatment over time. Relapsed/refractory (RRMM) is accompanied by the clonal evolution of cells heterogeneous genomic aberrations and profound changes bone marrow microenvironment (BME). However, molecular mechanisms that drive drug resistance remain elusive. Here, we analyze tumor cell population its complex interaction network BME 20 RRMM single RNA-sequencing before/after treatment. Subclones chromosome 1q-gain express a...
•TGR5 is downregulated in cholangiocytes PSC and Abcb4-/- livers a cell type-specific manner.•Interleukin-8 reduces TGR5 levels biliary epithelial cells organoids.•Biliary damage aggravated Tgr5-deficient mice attenuated overexpressing Tgr5.•ScRNA-seq shows that overexpression of Tgr5 ameliorates the activated, inflammatory phenotype.•norUDCA treatment restores Tgr5-expression mice. Background & AimsPrimary sclerosing cholangitis (PSC) characterized by chronic inflammation progressive...
Intratumor heterogeneity as a clinical challenge becomes most evident after several treatment lines, when multidrug-resistant subclones accumulate. To address this challenge, the characterization of resistance mechanisms at subclonal level is key to identify common vulnerabilities. In study, we integrate whole-genome sequencing, single-cell (sc) transcriptomics (scRNA sequencing), and chromatin accessibility (scATAC sequencing) together with mitochondrial DNA mutations define architecture...
Abstract Recent advances in the genomics of glioblastoma (GBM) led to introduction molecular neuropathology but failed translate into treatment improvement. This is largely attributed genetic and phenotypic heterogeneity GBM, which are considered major obstacle GBM therapy. Here, we use advanced human GBM-like organoid (LEGO: L aboratory E ngineered G lioblastoma-like O rganoid) models provide an unprecedented comprehensive characterization LEGO using single-cell transcriptome, DNA...
Medulloblastomas with extensive nodularity are cerebellar tumors characterized by two distinct compartments and variable disease progression. The mechanisms governing the balance between proliferation differentiation in MBEN remain poorly understood. Here, we employ a multi-modal single cell transcriptome analysis to dissect this process. In internodular compartment, identify proliferating granular neuronal precursor-like malignant cells, along stromal, vascular, immune cells. contrast,...
The bone marrow microenvironment plays a crucial role in the development of multiple myeloma. As disease progresses, malignant myeloma cells can evolve to survive outside marrow. However, processes underlying independence and their consequences for immune control remain poorly understood. Here, we conducted single-cell spatial multiomics analyses marrow-confined intramedullary paired breakout lesions that disrupt cortical bone. These revealed distinct cellular architectural features lesions,...