Tomáš Raček

Central European Institute of Technology – Masaryk University

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Radka Svobodová Vařeková

Central European Institute of Technology

Jaroslav Koča

Masaryk University

Aleš Křenek

Czech Academy of Sciences, Institute of Computer Science

Stanislav Geidl

Central European Institute of Technology

Václav Hejret

Central European Institute of Technology

Karel Berka

Palacký University Olomouc

Tomáš Bouchal

Central European Institute of Technology

Christoph Klein

Ludwig-Maximilians-Universität München

Jacek Puchałka

Ludwig-Maximilians-Universität München

Ondřej Schindler

Masaryk University

Cooperative Institutions

Roche (Switzerland)

Masaryk University

Ludwig-Maximilians-Universität München

Heidelberg University

Central European Institute of Technology – Masaryk University

Central European Institute of Technology

LMU Klinikum

Centre National de la Recherche Scientifique

Roche Pharma AG (Germany)

Imperial College London

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Deficiency Of JAGN1 Causes Severe Congenital Neutropenia Associated With Defective Secretory Pathway and Aberrant Myeloid Cell Homeostasis

Blood (2013)

Kaan Boztuğ Päivi M. Järvinen Elisabeth Salzer Tomáš Raček Sebastian Mönch

Congenital Neutropenia

Failure to Thrive

Sanger sequencing

10.1182/blood.v122.21.439.439

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Citations (3)

Molecular Mechanism of p73-Mediated Regulation of Hepatitis B Virus Core Promoter/Enhancer II: Implications for Hepatocarcinogenesis

Journal of Molecular Biology (2008)

Sven Buhlmann Tomáš Raček Alexandra Schwarz Stephan Schaefer Brigitte M. Pützer

Ectopic expression

Transcription

10.1016/j.jmb.2008.02.021

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Citations (13)

Transcriptional profiling upon T cell stimulation reveals down-regulation of inflammatory pathways in T and B cells in SLE versus Sjögren’s syndrome

npj Systems Biology and Applications (2023)

Gino Kwon Annika Wiedemann Lisa M. Steinheuer Ana‐Luisa Stefanski Franziska Szelinski

Abstract Systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) share clinical as well as pathogenic similarities. Although previous studies suggest various abnormalities in different immune cell compartments, dedicated cell-type specific transcriptomic signatures are often masked by patient heterogeneity. Here, we performed transcriptional profiling of isolated CD4, CD8, CD16 and CD19 lymphocytes from pSS and SLE patients upon T cell stimulation, in addition to a steady-state condition directly after blood drawing, in total comprising 581 sequencing samples. T cell stimulation, which induced a pronounced inflammatory response in all four cell types, gave rise to substantial re-modulation of lymphocyte subsets in the two autoimmune diseases compared to healthy controls, far exceeding the transcriptomic differences detected at steady-state. In particular, we detected cell-type and disease-specific down-regulation of a range of pro-inflammatory cytokine and chemokine pathways. Such differences between SLE and pSS patients are instrumental for selective immune targeting by future therapies.

Cell type

10.1038/s41540-023-00319-z

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Citations (2)

bio.tools Sum – tool for exploration of summary information about bioinformatics services in bio.tools

F1000Research (2018)

Tomáš Raček Radka Svobodová Vařeková Dan Polanský Karel Berka Jaroslav Koča

Open peer review

10.7490/f1000research.1115564.1

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MOESM7 of High-quality and universal empirical atomic charges for chemoinformatics applications

Figshare (2015)

Stanislav Geidl Tomáš Bouchal Tomáš Raček Radka Svobodová Vařeková Václav Hejret

Additional file 7: Table S4. R 2, RMSD, $${\overline{\Delta }}$$ Δ ¯ and coverage values of all tested EEM parameter sets on the extended test set.

Cheminformatics

10.6084/m9.figshare.c.3698527_d9

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Additional file 7 of Optimized SQE atomic charges for peptides accessible via a web application

Figshare (2021)

Ondřej Schindler Tomáš Raček Aleksandra Maršavelski Jaroslav Koča Karel Berka

Additional file 7. Parameter sets.All parameter sets obtained during the comparison of empirical methods.

10.6084/m9.figshare.14889576

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Transcriptional Repression of the Prosurvival Endoplasmic Reticulum Chaperone GRP78/BIP by E2F1

Journal of Biological Chemistry (2008)

Tomáš Raček Sven Buhlmann Franziska Rúst Susanne Knoll Vijay Alla

The endoplasmic reticulum chaperone GRP78/BIP plays a central role in the prosurvival machinery, and its enhanced expression has been implicated in drug resistance, carcinogenesis, and metastasis. E2F1, as part of an antitumor safeguard mechanism, promotes apoptosis regardless of functional p53. Using cells that are defective in p53, we show that E2F1 represses GRP78/BIP at the transcriptional level, and this requires its DNA binding domain. Analysis of human GRP78/BIP promoter reporter constructs revealed that the region between -371 and -109 of the proximal promoter contains major E2F1-responsive elements. Toward understanding the underlying mechanism of this regulation, we performed chromatin immunoprecipitation and gel shift assays, demonstrating that E2F1 directly binds to GC-rich regions in the distal GC-box and endoplasmic reticulum stress response element -126 by interfering with the binding of positive regulatory proteins Sp1 and TFII-I of the ER stress response element-binding factor complex. We further show that TFII-I, which is required for optimal stress induction of GRP78/BIP, is suppressed by E2F1 on the protein level. Finally, our studies suggest a molecular link between the inhibition of GRP78/BIP and E2F1-mediated chemosensitization of tumor cells, underscoring its relevance for cancer treatment. Together, the data provide a new mechanism for the incompletely understood tumor suppressor function of E2F1.

Chaperone (clinical)

10.1074/jbc.m803925200

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Citations (38)

Phase Ib study evaluating safety and clinical activity of the anti-HER3 antibody lumretuzumab combined with the anti-HER2 antibody pertuzumab and paclitaxel in HER3-positive, HER2-low metastatic breast cancer

Investigational New Drugs (2018)

Andreas Schneeweiß Tjoung‐Won Park‐Simon Joan Albanell Ulrik Lassen Javier Cortés

Summary Purpose To investigate the safety and clinical activity of comprehensive human epidermal growth factor receptor (HER) family receptor inhibition using lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with paclitaxel in patients with metastatic breast cancer (MBC). Methods This phase Ib study enrolled 35 MBC patients (first line or higher) with HER3-positive and HER2-low (immunohistochemistry 1+ to 2+ and in-situ hybridization negative) tumors. Patients received lumretuzumab (1000 mg in Cohort 1; 500 mg in Cohorts 2 and 3) plus pertuzumab (840 mg loading dose [LD] followed by 420 mg in Cohorts 1 and 2; 420 mg without LD in Cohort 3) every 3 weeks, plus paclitaxel (80 mg/m 2 weekly in all cohorts). Patients in Cohort 3 received prophylactic loperamide treatment. Results Diarrhea grade 3 was a dose-limiting toxicity of Cohort 1 defining the maximum tolerated dose of lumretuzumab when given in combination with pertuzumab and paclitaxel at 500 mg every three weeks. Grade 3 diarrhea decreased from 50% (Cohort 2) to 30.8% (Cohort 3) with prophylactic loperamide administration and omission of the pertuzumab LD, nonetheless, all patients still experienced diarrhea. In first-line MBC patients, the objective response rate in Cohorts 2 and 3 was 55% and 38.5%, respectively. No relationship between HER2 and HER3 expression or somatic mutations and clinical response was observed. Conclusions Combination treatment with lumretuzumab, pertuzumab and paclitaxel was associated with a high incidence of diarrhea. Despite the efforts to alter dosing, the therapeutic window remained too narrow to warrant further clinical development. Trial registration: on ClinicalTrials.gov with the identifier NCT01918254 first registered on 3rd July 2013.

Pertuzumab

Loperamide

10.1007/s10637-018-0562-4

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Citations (67)

MOESM6 of High-quality and universal empirical atomic charges for chemoinformatics applications

Figshare (2015)

Stanislav Geidl Tomáš Bouchal Tomáš Raček Radka Svobodová Vařeková Václav Hejret

Additional file 6: Charge details. Values of partial atomic charges (represented as tables and as graphs) for all tested EEM parameter sets on the testset.

Cheminformatics

10.6084/m9.figshare.c.3698527_d4

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MOESM9 of High-quality and universal empirical atomic charges for chemoinformatics applications

Figshare (2015)

Stanislav Geidl Tomáš Bouchal Tomáš Raček Radka Svobodová Vařeková Václav Hejret

Additional file 9: OpenBabel patch. A patch for OpenBabel, which enables it to use the EEM parameter sets calculated in this paper.

Cheminformatics

10.6084/m9.figshare.c.3698527_d8

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