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JRG VIII: Dr. Argyris Papantonis

· Systems biology of chromatin

My group’s aim is to understand how chromatin integrates signaling stimuli (like those of TNFα and TGFβ) to control gene expression. Genome architecture is thought to be a major determinant in this. We are particularly interested in the way effects on the ‘linear’ chromatin fibre translate into a 4-D network of interactions, i.e. in 3-D space and time.

We will apply a systems biology approach to track and correlate changes at the nascent transcriptome, proteome, and interactome levels. In the end, we anticipate the rules governing gene expression to be general ones, which – once deciphered – will allow us to predict how a cell might respond during disease or aging.



B1: Prof. Dr. Hinrich Abken

· Deciphering the hierarchic organization of established solid tumor lesions

Current concepts assume that cancer is originated by a defined subset of so-called cancer stem cells (CSCs); once the tumor is established all cancer cells have equal malignant capacities.
Our previous work, however, challenges the concept and provides strong evidence for a hierarchic organization of established tumor lesions in melanoma. Selective elimination of the 1-3% subset of CD20+ cancer cells from established melanoma lesions is particularly effective in tumor eradicating irrespective of the bulk of cancer cells.
Such "tumor sustaining cells" (TSCs) were most recently also identified in other cancer entities implying a broad relevance. The project aims at elucidating the mechanisms how CD20+ TSCs maintain their self-renewal and trigger progression of the majority of cancer cells. Work will underline an alternative concept of cancer as a top-down signaling network orchestrated by a minority of tumor sustaining cells and will provide a rationale to develop novel strategies in cancer therapy.



B2: Prof. Dr. Stephan Baldus / Dr. Anna Klinke / PD Dr. Volker Rudolph

· Significance of leukocyte-mediated impairment of vascular integrity for the pathogenesis of heart failure, and leukocyte peroxidase inhibition as a novel therapeutic concept

Leukocytes are strongly associated with the initiation and progression of heart failure, even though a direct contribution of the leukocyte to the myocyte´s integrity has not been demonstrated. However, there is firm evidence that leukocytes regulate vascular tone via release of vasoactive enzymes: Myeloperoxidase (MPO), a heme protein expressed and secreted by neutrophils and monocytes increases vascular tone by oxidation of nitric oxide. In clinical studies, increased circulating levels of MPO are found in patients with heart failure predicting the need for rehospitalization, transplantation and mortality. However, a clear mechanistic role of MPO in propagating heart failure and the distinct pathophysiological mechanisms have not been elucidated so far.

stephan.baldusSpamProtectionuk-koeln.de, anna.klinkeSpamProtectionuk-koeln.de, volker.rudolph@uk-koeln.de


B3: Prof. Dr. Thomas Benzing

· Dynamic roles of podocytes in glomerular filtration and the progression of chronic kidney disease SFB 572, SFB 635, SFB 829, SFB 832



B4: Dr. Mario Fabri

· Corticosteroid-mediated regulation of the human host response against intracellular pathogens  SFB 829



B5: Dr. Hamid Kashkar

· The ubiquitin ligase activity of XIAP in the pathogenesis of cancer SFB 832, SFB 670



B6: Prof. Dr. Martin Krönke / Prof. Dr. Olaf Utermöhlen

· NADPH oxidase (NOX)-generated reactive oxygen species (ROS): mechanisms of tissue-specific activation and pathophysiological implications for microbial infections SFB 832, SFB 670

m.kroenkeSpamProtectionuni-koeln.de, olaf.utermoehlenSpamProtectionuk-koeln.de


B7: Prof. Dr. Rudolf J. Wiesner

· How do mtDNA deletions lead to inflammation?