Peter Blattmann

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Blattmann

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Peter

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0000-0001-9105-6381

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Publications 1 - 10 of 11

Entry of Human Papillomavirus Type 16 by Actin-Dependent, Clathrin- and Lipid Raft-Independent Endocytosis
Schelhaas, Mario; Shah, Bhavin; Holzer, Michael; et al. (2012)
PLoS Pathogens
Infectious endocytosis of incoming human papillomavirus type 16 (HPV-16), the main etiological agent of cervical cancer, is poorly characterized in terms of cellular requirements and pathways. Conflicting reports attribute HPV-16 entry to clathrin-dependent and -independent mechanisms. To comprehensively describe the cell biological features of HPV-16 entry into human epithelial cells, we compared HPV-16 pseudovirion (PsV) infection in the context of cell perturbations (drug inhibition, siRNA silencing, overexpression of dominant mutants) to five other viruses (influenza A virus, Semliki Forest virus, simian virus 40, vesicular stomatitis virus, and vaccinia virus) with defined endocytic requirements. Our analysis included infection data, i.e. GFP expression after plasmid delivery by HPV-16 PsV, and endocytosis assays in combination with electron, immunofluorescence, and video microscopy. The results indicated that HPV-16 entry into HeLa and HaCaT cells was clathrin-, caveolin-, cholesterol- and dynamin-independent. The virus made use of a potentially novel ligand-induced endocytic pathway related to macropinocytosis. This pathway was distinct from classical macropinocytosis in regards to vesicle size, cholesterol-sensitivity, and GTPase requirements, but similar in respect to the need for tyrosine kinase signaling, actin dynamics, Na+/H+ exchangers, PAK-1 and PKC. After internalization the virus was transported to late endosomes and/or endolysosomes, and activated through exposure to low pH.
Quantitative Interactomics in Primary T Cells Provides a Rationale for Concomitant PD-1 and BTLA Coinhibitor Blockade in Cancer Immunotherapy
Celis-Gutierrez, Javier; Blattmann, Peter; Zhai, Yunhao; et al. (2019)
Cell Reports
Deciphering how TCR signals are modulated by coinhibitory receptors is of fundamental and clinical interest. Using quantitative interactomics, we define the composition and dynamics of the PD-1 and BTLA coinhibitory signalosomes in primary effector T cells and at the T cell-antigen-presenting cell interface. We also solve the existing controversy regarding the role of the SHP-1 and SHP-2 protein-tyrosine phosphatases in mediating PD-1 coinhibition. PD-1 predominantly recruits SHP-2, but when absent, it recruits SHP-1 and remains functional. In contrast, BTLA predominantly recruits SHP-1 and to a lesser extent SHP-2. By separately analyzing the PD-1-SHP-1 and PD-1-SHP-2 complexes, we show that both dampen the TCR and CD28 signaling pathways equally. Therefore, our study illustrates how comparison of coinhibitory receptor signaling via quantitative interactomics in primary T cells unveils their extent of redundancy and provides a rationale for designing combinations of blocking antibodies in cancer immunotherapy on the basis of undisputed modes of action.
Human SRMAtlas: A Resource of Targeted Assays to Quantify the Complete Human Proteome
Kusebauch, Ulrike; Campbell, David S.; Deutsch, Eric W.; et al. (2016)
Cell
Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer
Plattner, Christina; Lamberti, Giorgia; Blattmann, Peter; et al. (2023)
iScience
Precision oncology approaches for patients with colorectal cancer (CRC) continue to lag behind other solid cancers. Functional precision oncology—a strategy that is based on perturbing primary tumor cells from cancer patients—could provide a road forward to personalize treatment. We extend this paradigm to measuring proteome activity landscapes by acquiring quantitative phosphoproteomic data from patient-derived organoids (PDOs). We show that kinase inhibitors induce inhibitor- and patient-specific off-target effects and pathway crosstalk. Reconstruction of the kinase networks revealed that the signaling rewiring is modestly affected by mutations. We show non-genetic heterogeneity of the PDOs and upregulation of stemness and differentiation genes by kinase inhibitors. Using imaging mass-cytometry-based profiling of the primary tumors, we characterize the tumor microenvironment (TME) and determine spatial heterocellular crosstalk and tumor-immune cell interactions. Collectively, we provide a framework for inferring tumor cell intrinsic signaling and external signaling from the TME to inform precision (immuno-) oncology in CRC.
OMICS – Mass Spectrometry-Based Proteomics in Systems Biology Research
Blattmann, Peter; Aebersold, Rudolf (2023)
Encyclopedia of Cell Biology Second Edition
Mass spectrometry-based proteomics has already contributed greatly to systems biology studies and its role in systems biology research is likely to grow in the next few years. Its unique capability of quantifying proteins and protein modifications at large scale and throughput make it a prime technology in systems biology studies, specifically those focused on complex biological processes and diseases. In this article, we first introduce the motivation and challenges of using proteomics in systems biology studies. Second, we give an overview of the most common methods to measure and quantify proteins using liquid-chromatography coupled tandem mass spectrometry. In the third section, we highlight how mass spectrometry contributes to generating functionally highly relevant proteomic information that goes beyond the identity and quantity of constituent proteins (i.e., mapping the proteoforms, mapping the interactions, and relating the proteome to the genome), and then we focus on three exemplary biological processes to show how mass spectrometry-based studies contributed to increasing our understanding of them.
Mass Spectrometric Exploration of the Biochemical Basis of Living Systems
Abersold, Ruedi; Blattmann, Peter (2019)
Chimia
High-throughput proteomic analysis of FFPE tissue samples facilitates tumor stratification
Zhu, Yi; Weiss, Tobias; Zhang, Qiushi; et al. (2019)
Molecular Oncology
Formalin‐fixed, paraffin‐embedded (FFPE), biobanked tissue samples offer an invaluable resource for clinical and biomarker research. Here, we developed a pressure cycling technology (PCT)‐SWATH mass spectrometry workflow to analyze FFPE tissue proteomes and applied it to the stratification of prostate cancer (PCa) and diffuse large B‐cell lymphoma (DLBCL) samples. We show that the proteome patterns of FFPE PCa tissue samples and their analogous fresh‐frozen (FF) counterparts have a high degree of similarity and we confirmed multiple proteins consistently regulated in PCa tissues in an independent sample cohort. We further demonstrate temporal stability of proteome patterns from FFPE samples that were stored between 1 and 15 years in a biobank and show a high degree of the proteome pattern similarity between two types of histological regions in small FFPE samples, that is, punched tissue biopsies and thin tissue sections of micrometer thickness, despite the existence of a certain degree of biological variations. Applying the method to two independent DLBCL cohorts, we identified myeloperoxidase, a peroxidase enzyme, as a novel prognostic marker. In summary, this study presents a robust proteomic method to analyze bulk and biopsy FFPE tissues and reports the first systematic comparison of proteome maps generated from FFPE and FF samples. Our data demonstrate the practicality and superiority of FFPE over FF samples for proteome in biomarker discovery. Promising biomarker candidates for PCa and DLBCL have been discovered.
SWATH2stats: An R/bioconductor package to process and convert quantitative SWATH-MS proteomics data for downstream analysis tools
Blattmann, Peter; Heusel, Moritz; Aebersold, Ruedi (2016)
PLoS ONE
SWATH-MS is an acquisition and analysis technique of targeted proteomics that enables measuring several thousand proteins with high reproducibility and accuracy across many samples. OpenSWATH is popular open-source software for peptide identification and quantification from SWATH-MS data. For downstream statistical and quantitative analysis there exist different tools such as MSstats, mapDIA and aLFQ. However, the transfer of data from OpenSWATH to the downstream statistical tools is currently technically challenging. Here we introduce the R/Bioconductor package SWATH2stats, which allows convenient processing of the data into a format directly readable by the downstream analysis tools. In addition, SWATH2stats allows annotation, analyzing the variation and the reproducibility of the measurements, FDR estimation, and advanced filtering before submitting the processed data to downstream tools. These functionalities are important to quickly analyze the quality of the SWATH-MS data. Hence, SWATH2stats is a new open-source tool that summarizes several practical functionalities for analyzing, processing, and converting SWATH-MS data and thus facilitates the efficient analysis of large-scale SWATH/DIA datasets.
Generation of a zebrafish SWATH-MS spectral library to quantify 10,000 proteins
Blattmann, Peter; Stutz, Vivienne; Lizzo, Giulia; et al. (2019)
Scientific Data
Sequential window acquisition of all theoretical mass spectra (SWATH-MS) requires a spectral library to extract quantitative measurements from the mass spectrometry data acquired in data-independent acquisition mode (DIA). Large combined spectral libraries containing SWATH assays have been generated for humans and several other organisms, but so far no publicly available library exists for measuring the proteome of zebrafish, a rapidly emerging model system in biomedical research. Here, we present a large zebrafish SWATH spectral library to measure the abundance of 104,185 proteotypic peptides from 10,405 proteins. The library includes proteins expressed in 9 different zebrafish tissues (brain, eye, heart, intestine, liver, muscle, ovary, spleen, and testis) and provides an important new resource to quantify 40% of the protein-coding zebrafish genes. We employ this resource to quantify the proteome across brain, muscle, and liver and characterize divergent expression levels of paralogous proteins in different tissues. Data are available via ProteomeXchange (PXD010876, PXD010869) and SWATHAtlas (PASS01237).
A computational framework for the inference of protein complex remodeling from whole-proteome measurements
Buljan, Marija; Banaei Esfahani, Amir; Blattmann, Peter; et al. (2023)
Nature Methods
Protein complexes are responsible for the enactment of most cellular functions. For the protein complex to form and function, its subunits often need to be present at defined quantitative ratios. Typically, global changes in protein complex composition are assessed with experimental approaches that tend to be time consuming. Here, we have developed a computational algorithm for the detection of altered protein complexes based on the systematic assessment of subunit ratios from quantitative proteomic measurements. We applied it to measurements from breast cancer cell lines and patient biopsies and were able to identify strong remodeling of HDAC2 epigenetic complexes in more aggressive forms of cancer. The presented algorithm is available as an R package and enables the inference of changes in protein complex states by extracting functionally relevant information from bottom-up proteomic datasets.

Publications 1 - 10 of 11

Peter Blattmann

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