zum Inhalt springen

Research Area A: Mechanisms of tumor development: intrinsic and extrinsic control of cell proliferation and tissue invasion


AG Dr. Alessandro Annibaldi

· Understanding the role of cell death in health and disease

We are focussed on the role of cell death in health and disease. In particular, we investigate the molecular mechanisms regulating different forms of cell death (e.g. apoptosis and necroptosis) and how cell death contributes to inflammatory programs, activated following pathogenic infection or tissue damage, as well as to tumorigenesis. Understanding the complex relationship between cell death and inflammation will help to improve the current treatments of chronic inflammatory diseases and cancer.



AG Prof. Dr. Reinhard Büttner / Prof. Dr. Margarete Odenthal

· The multifaceted function of the lysine-specific histone demethylase 1 in lung cancer

Epigenetic abnormalities play a vital role in the progression of many cancer types including non-small cell lung cancer (NSCLC) which is a leading cause of cancer-related mortality. The lysine-specific demethylase 1 (LSD1/KDM1A) acts as an epigenetic regulator and is overexpressed in a wide variety of cancer types. In our studies, we address the mechanistic links of LSD1 function in NSCLC development using cancer-related cell systems and genetic mouse models.

reinhard.buettnerSpamProtectionuk-koeln.de, margarete.odenthalSpamProtectionuk-koeln.de


AG Prof. Dr. Christiane Bruns

· Relevance of the IL-17 immune response in a mouse model of pancreatic cancer and its modulation with mesenchymal stem cells

Aim: To elucidate if modulation of the IL-17 immune response with antibodies and mesenchymal stem cells (MSC) delays initiation, progression and dissemination of pancreatic ductal adenocarcinoma (PDAC).



AG Dr. Mathieu Clement-Ziza

· Mechanisms of tumor development: intrinsic and extrinsic control of cell proliferation and tissue invasion

Technological advances permit quantitative measurements of multiple biological characteristics at the genome-wide/system-wide level. Integrating, analysing and understanding these data is necessary to gain novel knowledge. Our research group embraces this data paradigm and develop system approaches to biological question. We work at the interface between molecular biology and computational biology.



AG Prof. Dr. Alexander Drzezga

· CXCR4 in kidney tumors

The translation of knowledge about CXCR4 expression from basic science into clinical practice by using Ga68-Pentixafor PET/CT may help for the in vivo characterization of kidney tumors with regard to aggressiveness, heterogeneity, prognosis, metastatic potential, therapy resistance and eligibility for novel therapy approaches.



AG Prof. Dr. Matthias Fischer

· The functional and therapeutic significance of activated telomerase in neuroblastoma

Neuroblastoma is malignant pediatric tumor with diverse clinical courses, ranging from spontaneous regression to fatal progression. Our findings establish a novel mechanistic classification of neuroblastoma that may benefit the clinical management of patients.



AG Prof. Dr. Jay Gopalakrishnan

· Targeting centrosome activation mechanisms to perturb cancer cell proliferation and invasion

Our aim was to apply our interdisciplinary expertise of genetics, biochemistry and structural biology to underpin how functional centrosomes are built and how do they control cell proliferation, differentiatuion and organ development.



AG Prof. Dr. Michael Hallek / Dr. Hien Nguyen

· Comprehensive analyses of the mechanistic role of LYN kinase in B cell malignancies

Chronic lymphocytic leukemia (CLL) is a malignant disease in which the survival of leukemic cells is strongly dependent of continuous stimulation by extracellular factors. We aim to explore this potential "Achilles heel" of CLL using a CLL mouse model and we work to develop novel therapeutic approaches in the future.

michael.hallekSpamProtectionuni-koeln.de, hien.nguyenSpamProtectionuk-koeln.de


AG Prof. Dr. Matthias Hammerschmidt

· The multiple facets of the type II transmembrane serine protease ST14 and hypotonic stress during carcinogenesis in fish and mammals

The cell surface-associated type II transmembrane protease matriptase 1 (MT-SP1, ST14) is implicated in the growth and invasion of multiple epithelial tumors, including ovarian, prostate, colorectal and skin cancer (Uhland, 2006; List, 2009). Several substrates of matriptase have been described, ranging from growth factors and their receptors to structural ECM proteins. However, no systematic searchers for matriptase substrates have been carried out as yet.


AG Dr. Robert Haensel-Hertsch

· (Epi)Genome structure and stability

Our lab explores the existence and significance of epigenome structural alterations for ageing and its impact on disease development



AG Dr. Marco Herling / Dr. Elena Vasyutina

· Context-specific mechanisms of the TCL1 oncogene in T- and B-cell leukemias

The proto-oncogene TCL1 is causally implicated in various B-cell and T-cell malignancies. Through a functional characterization of TCL1-engaged signaling networks and TCL1-centric therapeutic vulnerabilities, we addressed an essential scientific knowledge gap on the mechanisms of (chemo)therapy resistance in hematologic tumors.

marco.herlingSpamProtectionuk-koeln.de, elena.vasyutinaSpamProtectionuk-koeln.de


AG Dr. Roman-Ulrich Müller

· Characterizing the molecular functions of the tumor suppressor protein Folliculin using the model organism Caenorhabditis elegans

Birt-Hogg-Dubé syndrome is an autosomal dominant multitumor syndrome that is characterized by the triad of benign skin tumors, recurrent pneumothoraces and renal cyst and tumor formation. Germline mutations in Folliculin are the underlying cause of this syndrome.

In a recent study we have been able to introduce the nematode C. elegans as a novel model organism for studying the biology of BHD syndrome by characterizing a knockout strain of flcn-1, the worm homologue of Folliculin. Doing so we could confirm a previous report on a possible role of Folliculin in hypoxia-inducible factor signaling.
We will now continue this project using both cell culture and particularly the nematode model to examine the signaling pathways Folliculin is involved in more closely and to address a possible ciliary function of this tumor suppressor protein.



AG Dr. Sandra Iden:

· Requirement of polarity networks in melanoma cell plasticity, therapy and drug resistance

The establishment and maintenance of cellular polarity is crucial for tissue homeostasis, and its loss is a hallmark of carcinogenesis. This project aims to identify the role of conserved polarity proteins, master regulators of cytoarchitecture, in the initiation and progression of melanoma skin cancer. An ultimate goal is to translate the knowledge gained in this project into strategies for improved diagnosis and treatment of human melanoma.



AG Prof. Dr. Axel Heidenreich

Molecular mechanisms involved in migration, invasion and metastastic processes of testicular germ cell tumors


As with any given cancer TGCT consist of different cellular subpopulations with different abilities of growth, differentiation, metastatic potential, and drug resistance. TGCT are genetically heterogeneous and subpopulations with high metastatic potential may be present only in low quantities. The identification of specific biomarkers of such highly aggressive subpopulations represents a crucial issue in order to develop an individualized and risk adapted therapeutic approach in clinical stage I disease.



AG Dr. Catherin Niemann

· Mechanisms of stem cell-specific gatekeeper functions in cancer initiation

The overall goal is to understand cellular and molecular mechanisms that control adult epithelial stem cells, both under homeostatic and pathological conditions. Our research is focussing on epithelial stem cells of the skin that generate a diverse set of differentiated cell lineages, including keratinocytes of the interfollicular epidermis, hair follicles and sebaceous glands. We are investigating regulatory pathways of stem cell activation and lineage selection to explore their therapeutic value and we aim to identify the underlying molecular mechanisms of stem and progenitor cell activation in the process of epidermal tumour formation.



AG Dr. Maria Notara

· Effects of UV irradiation on corneal angiogenic privilege: pterygium as a UV-induced stem cell disease model: The limbal niche and corneal avascularity

The aim of this research group is to understand the mechanisms underlying the role of the limbal epithelial stem cells in corneal avascularity. Specifically, we are interested in the effect of UV irradiation on the limbal stem cell phenotype and pathological neovascularisation. 



AG Dr. Christian P Pallasch

· Functional implications and interaction of macrophages in the tumor microenvironment upon genotoxic stress



AG Prof. Dr. Manolis Pasparakis

· Immunogenic properties of necroptosis and apoptosis in stimulating anti-tumor immunity

Our studies aim to address the potential role of specific types of tumour cell death, namely necroptosis and apoptosis, in triggering anti-tumour immunity, and to explore their potential synergistic effect when combined with T cell activation checkpoint inhibitors. Our results may lead to the development of better immunotherapy protocols combining agents inducing specific types of cancer cell death with checkpoint inhibitors.



AG Dr. Martin Peifer / Prof. Dr. H. Christian Reinhardt

· Exploring actionable cooperating lesions that drive Myd88-mediated lymphomagenesis

Oncogenic MYD88mutations occur in 39% of all human activated B cell-type diffuse large B cell lymphomaS (ABC-DLBCL). Data from patients and our mouse models of Myd88-driven ABC-DLBCL indicate that Myd88mutations cooperate with additional genomic aberrations in ABC-DLBCL lymphomagenesis. MYD88 is a difficult drug target. Thus, we propose to search for druggable mutations that cooperate with MYD88in ABC-DLBCL lymphomagenesis. In addition, we propose a candidate approach for targeting MYD88-driven ABC-DLBCL in vivo, using IRAK4 inhibitors. 

mpeiferSpamProtectionuni-koeln.de, christian.reinhardtSpamProtectionuk-koeln.de


AG Dr. Martin Peifer

· Computational cancer genomics. Systematic identification of significantly mutated gene groups in cancer genomes by co-expression patterns

Whole-genome sequencing provides a portrait of all relevant genomic alterations in cancer genomes, whereas transcriptome sequencing yields a complete characterization of gene expression. Genomic alterations can be distinguished between random passenger mutations and drivers, where only driver mutations are contributing to pathogenesis. Their identification is therefore necessary to translate results from cancer genome analysis into new therapeutic strategies. However, single gene approaches are often limited by a lack of statistical power to detect rare events. To overcome this limitation, a systematic integration of transcriptome and genome-sequencing data may reveal groupings of rare driver events along paths of dysregulated genes. We propose a data-driven approach to, first, reduce complexity of the gene expression data and in a subsequent step, to map genomic alterations to resulting transcriptome profiles with the aim to identify connected groups of mutated and co-expressed genes



AG Dr. Simon Poepsel

· Structure and biochemistry of epigenetic regulators

As signals that orchestrate gene expression, cell differentiation and many other processes, these reactions have to be faithfully controlled. Our biochemical understanding of the multiprotein complexes that catalyze these reactions is still very limited. Therefore, we aim to define aspects of their context dependent, local activity regulation using cryo-electron microscopy (cryo-EM), biochemical and cell biological approaches.



AG Prof. Dr. Stephan Rosenkranz

· Role of PI3Kd in atherosclerosis

Recent projects utilizing genetic and pharmacological approaches have identified critical growth factor-dependent signaling mechanisms in atherosclerosis, neointima formation, pulmonary hypertension and heart failure, which gain insight into the pathogenic mechanisms of these diseases and serve as novel therapeutic targets.



AG Prof. Dr. Dr. Michal-Ruth Schweiger

· Epigenetic mechanisms of genomic instability and therapy resistance in cancer

It has long been thought that regions of constitutive heterochromatin are relatively devoid of genes and function as constitutive repressive regions. However, recent data indicates that constitutive heterochromatic regions are by far not silent and static. In contrast, during development and disease specific protein complexes are recruited and induce the expression of satellite RNA located at pericentromeric regions in various biological contexts such as differentiation, development, senescence, stress response and transformation.



AG Prof. Dr. Martin Sos

· Genomic and molecular characterization of the evolutionary process of drug resistance in EGFR-mutant lung cancer

Our project will strongly foster the basic understanding of tumor evolution, but will also offer insights that may rapidly be translated into clinical applications, such as improved therapies for patients with oncogenically driven lung cancer



AG Prof. Dr. Roman Thomas

· Lung Cancer Genomics

Our Lab Mission is to understand the impact of somatic genetic alterations in cancer cells on the highly complex regulatory network of signaling pathways.



AG Prof. Dr. Mirka Uhlirova

· Cutting through the tumor complexity: Role of splicing in epithelial homeostasis and tumorigenesis

Alterations of splicing factors in various human cancers prompted the development of spliceosome-targeting compounds, which showed marked anti-tumor effects and are now in clinical trials. Advancing our knowledge about individual splicing regulators in health and disease will yield additional therapeutic options with which splicing in tumor cells can be modulated or inhibited to block or reverse tumor development.



AG Prof. Dr. med. Dr. nat. med. Roland Ullrich

· Targeting tumor angiogenesis

We aim to define genetically encrypted correlates of tumor angiogenesis and tumor cell proliferation that enables to decipher new molecular therapeutically tractable targets. Another focus of our group are immunotherapeutic approaches and their combination with anti-angiogenetic treatment.



AG Prof. Dr. med. Dr. rer. nat. Michael von Bergwelt-Baildon

· Function of B cells in tertiary lymphoid structures in pancreatic tumors

Whether B cells promote or inhibit tumor growth seems to depend on a number of variables such as tumor type, stage and the dominating B cell subset. However, a high density of T and B cells in the tumor microenviroment is correlated with increased patient survival in several types of cancer. For many years, it was assumed that an adaptive anti-tumor immune response is elicited not in the tumor itself, but in secondary lymphoid organs (SLO). However recently, increasing evidence suggests that anti-tumor immune reactions may also be generated in the tumor microenvironment in so called tertiary lymphoid structures (TLS).