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Maciej Rosolowski

About Maciej Rosolowski:
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Health Atlas ID: 7WATJM05G3-0

Location:  Germany

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LIFE HNC - Head and Neck Cancer Group

The aim of the Head and Neck Group within the Leipzig Research Center for Civilization Diseases (LIFE) is to facilitate improvements in the treatment and care of head and neck cancer patients through insights from molecular studies.

The Head and Neck Group within the Leipzig Research Center for Civilization Diseases (LIFE) investigates the molecular mechanisms and the diagnostic and prognostic factors of head and neck cancer. For this purpose, we collected phenotypic information from about 300
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Programme: This Project is not associated with a Programme

Public web page: http://life.uni-leipzig.de/

Start date: 1st Jan 2012

End date: 31st Dec 2012

LIFE - Leipzig Research Center for Civilization Diseases: inactive since

Goal of the Leipzig Research Center for Civilization Diseases (LIFE) is the investigation of civilization diseases like depression, diabetes, allergies or cardiovascular diseases. For this purpose we collect as much data as possible regarding health and living conditions of the population in Leipzig and provide these data for scientists of the University of Leipzig and other research institutions.

Programme: Epidemiology

Public web page: http://life.uni-leipzig.de/

Start date: 1st Jan 2009

head and neck squamous cell carcinomas
LIFE HNC - Head and Neck Cancer Group

Stratification of head and neck squamous cell carcinomas (HNSCC) based on HPV16 DNA and RNA status

Snapshots: No snapshots

HNSCC
LIFE HNC - Head and Neck Cancer Group

Stratification of head and neck squamous cell carcinomas (HNSCC) based on HPV16 DNA and RNA status

Person responsible: Maciej Rosolowski

Snapshots: No snapshots

Study type: Clinical study (Phase 1)

HNSCC Clinical Dataset
LIFE HNC - Head and Neck Cancer Group
No description specified

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Snapshots: No snapshots

HNSCC OMICS Data
LIFE HNC - Head and Neck Cancer Group
No description specified

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Snapshots: No snapshots

Dynamics of cytokines, immune cell counts and disease severity in patients with community-acquired pneumonia - Unravelling potential causal relationships
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Community acquired pneumonia (CAP) is a severe and often rapidly deteriorating disease. To better understand its dynamics and potential causal relationships, we analyzed time series data of …f cytokines, blood and clinical parameters in hospitalized CAP patients. METHODS Time series data of 10 circulating cytokines, blood counts and clinical parameters were related to baseline characteristics of 403 CAP patients using univariate mixed models. Bivariate mixed models were applied to analyze correlations between the time series. To identify potential causal relationships, we inferred cross-lagged relationships between pairs of parameters using latent curve models with structured residuals. RESULTS IL-6 levels decreased faster over time in younger patients (Padj = 0.06). IL-8, VCAM-1, and IL-6 correlated strongly with disease severity as assessed by the sequential organ failure assessment (SOFA) score (r = 0.49, 0.48, 0.46, respectively; all Padj \textless 0.001). IL-6 and bilirubin correlated with respect to their mean levels and slopes over time (r = 0.36 and r = 0.46, respectively; Padj \textless 0.001). A number of potential causal relationships were identified, e.g., a negative effect of ICAM-1 on MCP-1, or a positive effect of the level of creatinine on the subsequent VCAM-1 concentration (P \textless 0.001). CONCLUSIONS These results suggest that IL-6 trajectories of CAP patients are associated with age and run parallel to bilirubin levels. The time series analysis also unraveled directed, potentially causal relationships between cytokines, blood parameters and clinical outcomes. This will facilitate the development of mechanistic models of CAP, and with it, improvements in treatment or surveillance strategies for this disease. TRIAL REGISTRATION clinicaltrials.gov NCT02782013, May 25, 2016, retrospectively registered.

Authors: Maciej Rosolowski, Volker Oberle, Peter Ahnert, Petra Creutz, Martin Witzenrath, Michael Kiehntopf, Markus Loeffler, Norbert Suttorp, Markus Scholz

Date Published: 1st Dec 2020

Publication Type: Journal article

Association of proteome and metabolome signatures with severity in patients with community-acquired pneumonia
Genetical Statistics and Systems Biology

Abstract (Expand)

A combined OMICS screening approach of human plasma and serum was used to characterize protein and metabolome signatures displaying association to severity of Community-acquired pneumonia (CAP). 240 … serum and BD P100 EDTA plasma samples from patients diagnosed with CAP, collected during the day of enrolment to the hospital, were analyzed by a metabolomic and proteomic approach, respectively. Disease severity of CAP patients was stratified using the Sequential Organ Failure Assessment (SOFA) score. Quantitative proteome and metabolome data, derived by LC-MS/MS, were associated to SOFA and specific parameters of SOFA using linear regression models adjusted for age, BMI, sex, smoking and technical variables. Both proteome and metabolome profiling revealed remarkable strong changes in plasma and serum composition in relation to severity of CAP. Proteins and metabolites displaying SOFA associated levels are involved in immune response, particularly in processes of lipid metabolism. Proteins, which show an association to SOFA score, are involved in acute phase response, coagulation, complement activation and inflammation. Many of these metabolites and proteins displayed not only associations to SOFA, but also to parameters of SOFA score, which likely reflect the strong influence of lung-, liver-, kidney- and heart-dysfunction on the metabolome and proteome patterns. SIGNIFICANCE: Community-acquired pneumonia is the most frequent infection disease with high morbidity and mortality. So far, only few studies focused on the identification of proteins or metabolites associated to severity of CAP, often based on smaller sample sets. A screening for new diagnostic markers requires extensive sample collections in combination with high quality clinical data. To characterize the proteomic and metabolomics pattern associated to severity of CAP we performed a combined metabolomics and proteomic approach of serum and plasma sample from a multi-center clinical study focused on patients with CAP, requiring hospitalization. The results of this association study of omics data to the SOFA score enable not only an interpretation of changes in molecular patterns with severity of CAP but also an assignment of altered molecules to dysfunctions of respiratory, renal, coagulation, cardiovascular systems as well as liver.

Authors: Manuela Gesell Salazar, Sophie Neugebauer, Tim Kacprowski, Stephan Michalik, Peter Ahnert, Petra Creutz, Maciej Rosolowski, Markus Löffler, Michael Bauer, Norbert Suttorp, Michael Kiehntopf, Uwe Völker

Date Published: 1st Mar 2020

Publication Type: Journal article

Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome.
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Colorectal cancer (CRC) arising in Lynch syndrome (LS) comprises tumours with constitutional mutations in DNA mismatch repair genes. There is still a lack of whole-genome and transcriptome studies of … LS-CRC to address questions about similarities and differences in mutation and gene expression characteristics between LS-CRC and sporadic CRC, about the molecular heterogeneity of LS-CRC, and about specific mechanisms of LS-CRC genesis linked to dysfunctional mismatch repair in LS colonic mucosa and the possible role of immune editing. Here, we provide a first molecular characterization of LS tumours and of matched tumour-distant reference colonic mucosa based on whole-genome DNA-sequencing and RNA-sequencing analyses. Our data support two subgroups of LS-CRCs, G1 and G2, whereby G1 tumours show a higher number of somatic mutations, a higher amount of microsatellite slippage, and a different mutation spectrum. The gene expression phenotypes support this difference. Reference mucosa of G1 shows a strong immune response associated with the expression of HLA and immune checkpoint genes and the invasion of CD4+ T cells. Such an immune response is not observed in LS tumours, G2 reference and normal (non-Lynch) mucosa, and sporadic CRC. We hypothesize that G1 tumours are edited for escape from a highly immunogenic microenvironment via loss of HLA presentation and T-cell exhaustion. In contrast, G2 tumours seem to develop in a less immunogenic microenvironment where tumour-promoting inflammation parallels tumourigenesis. Larger studies on non-neoplastic mucosa tissue of mutation carriers are required to better understand the early phases of emerging tumours. Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Authors: H. Binder, L. Hopp, M. R. Schweiger, S. Hoffmann, F. Juhling, M. Kerick, B. Timmermann, S. Siebert, C. Grimm, L. Nersisyan, A. Arakelyan, M. Herberg, P. Buske, H. Loeffler-Wirth, M. Rosolowski, C. Engel, J. Przybilla, M. Peifer, N. Friedrichs, G. Moeslein, M. Odenthal, M. Hussong, S. Peters, S. Holzapfel, J. Nattermann, R. Hueneburg, W. Schmiegel, B. Royer-Pokora, S. Aretz, M. Kloth, M. Kloor, R. Buettner, J. Galle, M. Loeffler

Date Published: 21st Jul 2017

Publication Type: Not specified

Human Diseases: Lynch syndrome, colorectal cancer

The role of HPV RNA transcription, immune response-related gene expression and disruptive TP53 mutations in diagnostic and prognostic profiling of head and neck cancer.
LIFE HNC - Head and Neck Cancer Group, Genetical Statistics and Systems Biology

Abstract (Expand)

Stratification of head and neck squamous cell carcinomas (HNSCC) based on HPV16 DNA and RNA status, gene expression patterns, and mutated candidate genes may facilitate patient treatment decision. We … characterize head and neck squamous cell carcinomas (HNSCC) with different HPV16 DNA and RNA (E6*I) status from 290 consecutively recruited patients by gene expression profiling and targeted sequencing of 50 genes. We show that tumors with transcriptionally inactive HPV16 (DNA+ RNA-) are similar to HPV-negative (DNA-) tumors regarding gene expression and frequency of TP53 mutations (47%, 8/17 and 43%, 72/167, respectively). We also find that an immune response-related gene expression cluster is associated with lymph node metastasis, independent of HPV16 status and that disruptive TP53 mutations are associated with lymph node metastasis in HPV16 DNA- tumors. We validate each of these associations in another large data set. Four gene expression clusters which we identify differ moderately but significantly in overall survival. Our findings underscore the importance of measuring the HPV16 RNA (E6*I) and TP53-mutation status for patient stratification and identify associations of an immune response-related gene expression cluster and TP53 mutations with lymph node metastasis in HNSCC.

Authors: G. Wichmann, M. Rosolowski, K. Krohn, M. Kreuz, A. Boehm, A. Reiche, U. Scharrer, D. Halama, J. Bertolini, U. Bauer, D. Holzinger, M. Pawlita, J. Hess, C. Engel, D. Hasenclever, M. Scholz, P. Ahnert, H. Kirsten, A. Hemprich, C. Wittekind, O. Herbarth, F. Horn, A. Dietz, M. Loeffler

Date Published: 15th Dec 2015

Publication Type: Not specified

Human Diseases: head and neck cancer

The PCBP1 gene encoding poly(rC) binding protein I is recurrently mutated in Burkitt lymphoma.
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

The genetic hallmark of Burkitt lymphoma is the translocation t(8;14)(q24;q32), or one of its light chain variants, resulting in IG-MYC juxtaposition. However, these translocations alone are insufficient … to drive lymphomagenesis, which requires additional genetic changes for malignant transformation. Recent studies of Burkitt lymphoma using next generation sequencing approaches have identified various recurrently mutated genes including ID3, TCF3, CCND3, and TP53. Here, by using similar approaches, we show that PCBP1 is a recurrently mutated gene in Burkitt lymphoma. By whole-genome sequencing, we identified somatic mutations in PCBP1 in 3/17 (18%) Burkitt lymphomas. We confirmed the recurrence of PCBP1 mutations by Sanger sequencing in an independent validation cohort, finding mutations in 3/28 (11%) Burkitt lymphomas and in 6/16 (38%) Burkitt lymphoma cell lines. PCBP1 is an intron-less gene encoding the 356 amino acid poly(rC) binding protein 1, which contains three K-Homology (KH) domains and two nuclear localization signals. The mutations predominantly (10/12, 83%) affect the KH III domain, either by complete domain loss or amino acid changes. Thus, these changes are predicted to alter the various functions of PCBP1, including nuclear trafficking and pre-mRNA splicing. Remarkably, all six primary Burkitt lymphomas with a PCBP1 mutation expressed MUM1/IRF4, which is otherwise detected in around 20-40% of Burkitt lymphomas. We conclude that PCBP1 mutations are recurrent in Burkitt lymphomas and might contribute, in cooperation with other mutations, to its pathogenesis.

Authors: R. Wagener, S. M. Aukema, M. Schlesner, A. Haake, B. Burkhardt, A. Claviez, H. G. Drexler, M. Hummel, M. Kreuz, M. Loeffler, M. Rosolowski, C. Lopez, P. Moller, J. Richter, M. Rohde, M. J. Betts, R. B. Russell, S. H. Bernhart, S. Hoffmann, P. Rosenstiel, M. Schilhabel, M. Szczepanowski, L. Trumper, W. Klapper, R. Siebert

Date Published: 16th Jul 2015

Publication Type: Not specified

Human Diseases: lymphoma

Massive Transcriptional Perturbation in Subgroups of Diffuse Large B-cell Lymphomas
MMML-MYC-SYS

Based on the assumption that molecular mechanisms involved in cancerogenesis are characterized by groups of coordinately expressed genes, we developed and validated a novel method for analyzing transcriptional data called Correlated Gene Set Analysis (CGSA). Using 50 extracted gene sets we identified three different profiles of tumors in a cohort of 364 Diffuse large B-cell (DLBCL) and related mature aggressive B-cell lymphomas other than Burkitt lymphoma. The first profile had high level of
...

Creator: Maciej Rosolowski

Submitter: Christoph Beger

Data file type: Transcriptomic Data

Human Diseases: diffuse large B-cell lymphoma

External Link
GSE 65858 ODM
LIFE HNC - Head and Neck Cancer Group

Our first objective was to compare the molecular features of subgroups of HNSCC defined by their HPV16 DNA and RNA status. The second objective was to identify gene expression subtypes in HNSCC and to correlate them with other characteristics of the patients.

HPV DNA and RNA status, mutations of 50 genes, survival and other clinical characteristics of 270 patients with head and neck cancer.

Creator: Maciej Rosolowski

Submitter: René Hänsel

Data file type: ODM Data

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GSE 65858 CSV
LIFE HNC - Head and Neck Cancer Group

Our first objective was to compare the molecular features of subgroups of HNSCC defined by their HPV16 DNA and RNA status. The second objective was to identify gene expression subtypes in HNSCC and to correlate them with other characteristics of the patients.

HPV DNA and RNA status, mutations of 50 genes, survival and other clinical characteristics of 270 patients with head and neck cancer.

Creator: Maciej Rosolowski

Submitter: René Hänsel

Data file type: Clinical Data

Download
GSE 65858 XLS
LIFE HNC - Head and Neck Cancer Group

Our first objective was to compare the molecular features of subgroups of HNSCC defined by their HPV16 DNA and RNA status. The second objective was to identify gene expression subtypes in HNSCC and to correlate them with other characteristics of the patients.

HPV DNA and RNA status, mutations of 50 genes, survival and other clinical characteristics of 270 patients with head and neck cancer.

Creator: Maciej Rosolowski

Submitter: René Hänsel

Data file type: Clinical Data

Download
Gene expression patterns and TP53 mutations are associated with HPV RNA status, lymph node metastasis, and survival in head and neck cancer (clinical Dataset)
LIFE HNC - Head and Neck Cancer Group

Our first objective was to compare the molecular features of subgroups of HNSCC defined by their HPV16 DNA and RNA status. The second objective was to identify gene expression subtypes in HNSCC and to correlate them with other characteristics of the patients.

HPV DNA and RNA status, mutations of 50 genes, survival and other clinical characteristics of 270 patients with head and neck cancer.

Creator: Maciej Rosolowski

Submitter: Christoph Beger

Data file type: Clinical Data

Human Diseases: head and neck squamous cell carcinoma

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CAP Severity Scores
Genetical Statistics and Systems Biology

This Shiny-App implements the calculation of several CAP (Community-Aquired-Pneumonia) severity scores for one or multiple patients based on user-updated data.

Creators: Markus Scholz, Maciej Rosolowski, Carl Beuchel

Submitter: Carl Beuchel

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Additional survival analyses of the data set from Wichmann et al. (Int. J. Canc. 2015). Head and neck tumor patients. Overall survival.
LIFE HNC - Head and Neck Cancer Group
No description specified

Creator: Maciej Rosolowski

Submitter: René Hänsel

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