Florian Uhlitz
A5073587449- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Ferroptosis and cancer prognosis
- Melanoma and MAPK Pathways
- Computational Drug Discovery Methods
- Immune Cell Function and Interaction
- Gene expression and cancer classification
- Gene Regulatory Network Analysis
- Bioinformatics and Genomic Networks
- Genomics and Chromatin Dynamics
- Evolution and Genetic Dynamics
- Cell Image Analysis Techniques
- Colorectal Cancer Treatments and Studies
- Receptor Mechanisms and Signaling
- Genetic factors in colorectal cancer
- Immune cells in cancer
- Ovarian cancer diagnosis and treatment
- Protein Degradation and Inhibitors
- Radiomics and Machine Learning in Medical Imaging
- RNA modifications and cancer
- interferon and immune responses
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
Charité - Universitätsmedizin Berlin
2017-2024
Kettering University
2022-2024
Memorial Sloan Kettering Cancer Center
2021-2024
Humboldt-Universität zu Berlin
2017-2021
Freie Universität Berlin
2020-2021
German Cancer Research Center
2019-2021
Heidelberg University
2019-2021
Aberrant cell signaling can cause cancer and other diseases is a focal point of drug research. A common approach to infer activity pathways from gene expression. However, mapping expression pathway components disregards the effect post-translational modifications, downstream signatures represent very specific experimental conditions. Here we present PROGENy, method that overcomes both limitations by leveraging large compendium publicly available perturbation experiments yield core Pathway...
Abstract High-grade serous ovarian cancer (HGSOC) is an archetypal of genomic instability 1–4 patterned by distinct mutational processes 5,6 , tumour heterogeneity 7–9 and intraperitoneal spread 7,8,10 . Immunotherapies have had limited efficacy in HGSOC 11–13 highlighting unmet need to assess how the anatomical sites foci determine immunological states microenvironment. Here we carried out integrative analysis whole-genome sequencing, single-cell RNA digital histopathology multiplexed...
Abstract Recent developments in immuno-oncology demonstrate that not only cancer cells, but also the tumor microenvironment can guide precision medicine. A comprehensive and in-depth characterization of is challenging since its cell populations are diverse be important even if scarce. To identify clinically relevant microenvironmental features, we applied single-cell RNA sequencing to ten human lung adenocarcinomas normal control tissues. Our analyses revealed heterogeneous carcinoma...
How cell-to-cell copy number alterations that underpin genomic instability
Article3 May 2017Open Access Source DataTransparent process An immediate–late gene expression module decodes ERK signal duration Florian Uhlitz orcid.org/0000-0001-9176-4660 IRI Life Sciences & Institute for Theoretical Biology, Humboldt Universität Berlin, Germany of Pathology, Charité – Universitätsmedizin Search more papers by this author Anja Sieber Emanuel Wyler Berlin Medical Systems Max Delbrück Center Molecular Medicine, Raphaela Fritsche-Guenther Johannes Meisig Markus Landthaler...
Oncoproteins such as the BRAFV600E kinase endow cancer cells with malignant properties, but they also create unique vulnerabilities. Targeting of BRAFV600E-driven cytoplasmic signaling networks has proved ineffective, patients regularly relapse reactivation targeted pathways. We identify nuclear protein SFPQ to be synthetically lethal in a loss-of-function shRNA screen. depletion decreases proliferation and specifically induces S-phase arrest apoptosis colorectal melanoma cells....
ABSTRACT Whole-genome doubling (WGD) is a critical driver of tumor development and linked to drug resistance metastasis in solid malignancies. Here, we demonstrate that WGD an ongoing mutational process evolution. Using single-cell whole-genome sequencing, measured modeled how events are distributed across cellular populations within tumors associated dynamics with properties genome diversification phenotypic consequences innate immunity. We studied evolution 65 high-grade serous ovarian...
Abstract Deciphering individual cell phenotypes from cell-specific transcriptional processes requires high dimensional single RNA sequencing. However, current dimensionality reduction methods aggregate sparse gene information across cells, without directly measuring the relationships that exist between genes. By performing with respect to co-expression, low-dimensional features can model these gene-specific and leverage shared signal overcome sparsity. We describe GeneVector, a scalable...
Abstract Deciphering individual cell phenotypes from cell-specific transcriptional processes requires high dimensional single RNA sequencing. However, current dimensionality reduction methods aggregate sparse gene information across cells, without directly measuring the relationships that exist between genes. By performing with respect to co-expression, low-dimensional features can model these gene-specific and leverage shared signal overcome sparsity. We describe GeneVector, a scalable...
Abstract In colorectal cancer, oncogenic mutations transform a hierarchically organized and homeostatic epithelium into invasive cancer tissue lacking visible organization. We sought to define cell types signals controlling their development. More than 30,000 epithelial single transcriptomes of tumors matched non-cancerous tissues twelve patients were clustered six patient-overarching groups defined by differential activities signaling pathways such as mitogen-activated protein kinase traits...
ABSTRACT High-grade serous ovarian cancer (HGSOC) is an archetypal of genomic instability patterned by distinct mutational processes, intratumoral heterogeneity and intraperitoneal spread. We investigated determinants immune recognition evasion in HGSOC to elucidate co- evolutionary processes underlying malignant progression tumor immunity. Mutational anatomic sites foci were key microenvironment cellular phenotypes, inferred from whole genome sequencing, single-cell RNA digital...
ABSTRACT Structural genome alterations are determinants of cancer ontogeny and therapeutic response. While bulk sequencing has enabled delineation structural variation (SV) mutational processes which generate patterns DNA damage, we have little understanding how these lead to cell-to-cell variations underlie selection rates accrual different genomic lesions. We analysed 309 high grade serous ovarian triple negative breast genomes determine their processes, selecting 22 from sequenced...
Abstract Cancer genomes exhibit extensive chromosomal copy number changes and structural variation, yet how allele specific alterations drive cancer genome evolution remains unclear. Here, through application of a new computational approach we report in 11,097 single cell whole from genetically engineered mammary epithelial cells 21,852 high grade serous ovarian triple negative breast cancers. Resolving profiles to individual alleles uncovered genomic background distributions gains, losses...
Abstract The MAPK pathway is an important cellular signaling cascade whose dysregulation causes a variety of diseases. While the upstream regulators this have been extensively characterized, understanding how its activation translates into different transcriptional responses remains poorly understood. This study attempts to fill knowledge gap by using targeted Perturb-seq against 22 transcription factors in inducible model system for RAF-MAPK signaling. A topology-based modeling approach...
Abstract Chromosomal instability (CIN) is a major driver of tumor progression and treatment resistance in many cancers. CIN characterized by ongoing chromosome missegregation, segmental aneuploidy whole-genome doubling (WGD), generating copy number heterogeneity that provides substrate for natural selection. Although well model systems, the evolutionary dynamics genomic impact WGD underexplored primary tumors metastases. Newly developed single-cell genomics assays now allow measurement whole...
Abstract High-grade serous ovarian cancer (HGSOC) is an archetypal of genomic instability patterned by distinct mutational processes, a high degree tumor heterogeneity and intraperitoneal spread. As immunotherapies have thus far proven ineffective in this disease, we sought to establish the determinants immune recognition, avoidance evasion disease natural history gain insight into co-evolutionary processes underlying malignant progression host immunity. Accordingly linked anatomic sites...
Abstract Chromosomal instability (CIN) is a major driver of tumor progression and treatment resistance in many cancers. CIN characterized by ongoing chromosome missegregation, generating copy number heterogeneity that provides substrate for natural selection. Although has been well studied model systems, the evolutionary dynamics genomic impact underexplored primary tumors metastases. Newly developed single cell genomics assays allow measurement whole genomes cells obtained from patient...
Introduction Oncogenic KRAS is widely acknowledged as a critical determinant of the therapeutic response colorectal cancer (CRC) – fact that to date pivotal for defining an appropriate treatment strategy. Whether this also extends beyond RTK- and MAPK- targeted molecular therapies, novel promising class anti-cancer drugs, namely HDAC inhibitors (HDACi), aspect until now has remained largely undefined. Our aim is, therefore, establish whether RAS effective predictor HDACi in CRC. Ultimately,...