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Fakultäten » Medizinische Fakultät » Dermatologische Klinik » Prof. Dr. Reinhard Dummer » Dummer

Current research project

Title / Titel Transcriptional adaptive response caused by different therapies in Cutaneous T-Cell Lymphomas
PDF Abstract (PDF, 14 KB)
Original title / Originaltitel Transcriptional adaptive response caused by different therapies Cutaneous T-Cell Lymphomas
Summary / Zusammenfassung Primary cutaneous T-cell lymphomas (CTCL) represent the most common subgroup of cutaneous lymphomas. CTCL are characterized by the initial accumulation of malignant CD4+ T-cells with memory phenotype in the skin. CTCL patients suffer severely from disfiguring skin lesions, ulcerations and itch. Despite the broad spectrum of therapeutic interventions, curative treatment for CTCL is missing.
Several studies have attempted to clarify the pathogenic events in CTCL. Molecular studies of timour cells (TCs) have revealed existence of several genetic defects and disturbances on transcriptional level. Large scale evaluation of polymorphic markers, such as single nucleotide polymorphisms (SNPs), as well as expression profiling has provided a comprehensive tool for analyzing changes in human genome or transcriptome, revealing genomic aberrations and patterns of deregulated gene expression contributing to the cancer phenotype.
Using high-throughput transcriptional profiling we plan to evaluate the level of transcriptome adaptation to therapeutic interventions for CTCL treatment. Pre-, on- and after -treatment biopsies will be collected and compared. In order to provide "etalon" samles for data analysis comparing patient samples to published data CTCL cell lines will be used. Human Exon 1.0 ST microarrays by Affymetrix will be used to assess transcriptional changes. The overall goal of the proposed project is to determine the spectrum (quality) and the frequency (quantity) of transcriptional alterations in CTCL patients underwent different cancer therapy. During data mining phase of the project the amount of transcriptional adaptation will be assessed on exon level to determine functional aspects of the changes and contribute to the development of personalized treatment approach for CTCL.
The unique novelty of this project lies within the combination of therapeutic intervention and following transcriptome profiling using latest available technology. This will allow to identify alterations associated with the pathogenesis of the disease, as well as to define new genetic markers for the CTCLs, which could be implemented in clinical practice. This project will help to define new disease-specific target(s) that may be implemented in the diagnostics and therapeutic interventions. Taking into account the lack of tumor-targeted therapies in CTCLs, this study may help to initiate the development of therapeutic strategies targeting behavior of leukemic T cells and improve the quality of life, not only in CTCL, but also in other T cell malignancies
Keywords / Suchbegriffe CTCL, targeted therapy, microarrays, HDAC inhibitors, bexarotene, doxorubicin
Project leadership and contacts /
Projektleitung und Kontakte
Prof. Dr. Reinhard Dummer, MD (Project Leader) reinhard.dummer@usz.ch
Dr. Maria B. Karpova, PhD maria.karpova@usz.ch
Dr. Sima Rozati, MD sima.rozati@usz.ch
Funding source(s) /
Unterstützt durch
Private Sector (e.g. Industry), Others
 
In collaboration with /
In Zusammenarbeit mit
Dr. Michal Okoniweski, PhD
Functional Genomic Centre
University of Zurich
Switzerland
Duration of Project / Projektdauer Jul 2010 to Mar 2013