Oncology

Within oncology the focus is on seeking to understand the basic molecular biological processes of tumour biology in order to develop new treatment methods. Participating researchers from biology as well as experimental and clinical medicine are investigating tumours as “biological systems” and so-called “neo-organs”. A variety of modern approaches, experimental systems and methods for the analysis of tumour development, growth, progression, tumour cell migration and therapy resistance are available.

Oncological research is one of the main areas of research at the UK Essen and the medical faculty. The West German Tumour Centre (WTZ) is the central structure for clinical, translational and basic research in this field. Since 2009 it has been continuously supported by German Cancer Aid as an “Oncological Top Centre/Comprehensive Cancer Centre” and is the only centre of this kind in the Ruhr Metropolitan Region supported by German Cancer Aid. Since 2019, the Oncology Centre of Essen University Hospital has also been cooperating with the Münster WTZ network partner (Center for Cancer Medicine at Münster University Hospital) under the umbrella of the WTZ. In 2018, a cooperation agreement was signed with the Center for Integrated Oncology (CIO) of the University Clinics Cologne/Bonn to establish the Cancer Center Cologne Essen (CCCE), with the aim of further structuring and focusing on oncological research and patient care at the two major cancer centres and accelerating the transfer of the latest findings into improved diagnosis and treatment. In addition, the WTZ is one of the seven sites of the German Consortium for Translational Cancer Research (DKTK), which together with the German Cancer Research Centre in Heidelberg (DKFZ) represents the German Centre for Health Research (DZG) for Applied Cancer Research funded by the Federal Ministry of Education and Research (BMBF) and the host regions.

A selection of the current joint projects

Coordination by UDE/UK Essen

DFG

Priority Programme SPP 1629 THYROID TRANS ACT – Translation of Thyroid Hormone Actions beyond Classical Concepts; Prof. Dagmar Führer-Sakel

Clinical Research Unit KFO 337 PhenoTImE – Phenotypic therapy and immune resistance in cancer; Profs. Dirk Schadendorf and Alexander Roesch

German Cancer Aid

Regulators of tumour plasticity as therapeut­ic target structures with ductal pancreatic carcinomas; Prof. Jens Siveke

T-Lock – Understanding T cell resistance in immune checkpoint blocking tumour therapy; Prof. Annette Paschen

COST – European Network of Investigators Mye-EUNITER – Triggering Exploratory Research on Myeloid Regulatory Cells, Prof. Sven Brandau

DKTK Joint Funding Projects

Overcoming therapy resistance in pancreatic cancers; Prof. Jens Siveke

Targeting MYC; Prof. Jens Siveke amongst others

Participation by the UDE/UK Essen

CRC 876 Availability of information through analysis under resource constraints

Research Unit FOR 1961 Mature T-cell lymphomas – mechan­isms of perturbed clonal T-cell homeostasis

Preventive strategies against brain metastases; German Cancer Aid

ERANets on Translational Cancer Research

CEVIR – Cancer evolution and identification of relapse-initiating cells

ARREST – Approaching recurrence and resistance mechanisms in esophagogastric adenocarcinomas from the prospective MEMORI trial

NIRBTEST – New strategies to detect cancers in carriers of mutations in RB1: blood tests based on tumor-educated platelets, or extracellular vesicle

Lead Market “LifeSciences.NRW” ProjectRIST

Ras Inhibition in Solid Tumours

ICAN33 – Development of an immuno­therapy for acute myeloid leukaemia (AMLs) by using allogeneic natural killer (NK) cells with CD33 CARs

BMBF projects ZiSStrans – Target structures of individual radiation sensitivity and CTCelect

DKTK, NEO-ATT – Clinical development of lead NEOantigen-specific T cell receptors for Adoptive T cell Therapy of solid tumors

DKTK Joint Funding Projects DKTK Master, DKTK-PARADIGM and UniCAR NK cells

Immunology, infectious diseases and transplantation

The immune system has developed different mechanisms to respond to a variety of pathogens such as viruses and bacteria, to prevent disease and to prevent the persistence of the pathogen in the infected organism. However, many pathogens have developed mechanisms to evade the immune system. In this programme, the molecular and cellular inter­actions of pathogens with the immune system are investigated with the aim of understanding the basic mechanisms of these interactions and deriving new strategies for immunotherapy or vaccination. One focus of transplantation research is on immunogenetics and diagnostics in order to understand the triggering of the immune response, to avoid rejection reactions and to optimize the identification of donors and recipients. In addition, the differentiation of lymphocytes is investigated. The participating research groups are pursuing scientific and clinical approaches.

Immunology and infectiology together form one of five research areas at the Medical Faculty of the UDE, which has positioned itself both nationally and internationally as a strong research site in the field of infection research. Since 2013, the West German Centre for Infectiology has been coordinating all the clinical and scientific areas of infectious medicine that focus on the research, prevention, diagnosis and therapy of infectious diseases.

A selection of the current joint projects

Coordination by UDE/UK Essen

Lead Market “LifeSciences.NRW” Projects SEVRIT – Production and quality assurance of stem cell-derived extracellular vesicles for new regenerative and immunomodulating therapeutic approaches, including Profs. Peter Horn/Bernd Giebel

Lead Market “LifeSciences.NRW” Project BluStar.NRW network for the typing of potential blood and stem cell donors among refugees and migrants in North Rhine-Westphalia; Prof. Peter Horn

BMBF HotAcidFACTORY – Sulfolobus acidocaldarius as novel thermoacidophilic bio-factory; Prof. Bettina Siebers

ERA Cofund on Biotechnologies HotSolute –Thermophilic bacterial and archaeal chassis for extremolyte production; Prof. Bettina Siebers

Participation by UDE/UK Essen

Research Unit FOR 2123 Sphingolipid dynamics in infection control

Research Unit FOR 2879 ImmunoStroke: From the immune cell to stroke regeneration

CRC 974 Communication and systemic rele­vance in liver damage and regeneration

Priority Programme SPP 1923 Innate sensing and restriction of retroviruses

FP7 MATHIAS – New Molecular-Functional Imaging Technologies and Therapeutic Strat­egies for Theranostic of Invasive Aspergillosis

H2020

Multimot – Capture, dissemination and analysis of multiscale cell migration data for biological and clinical applications

EVPRO – Development of Extracellular Vesicles loaded hydrogel coatings with immunomodulatory activity

AutoCRAT – Automated Cellular Robot-Assisted Technologies for translation of discovery-led research in Osteoarthritis

ERA-Net EuroTransBio. EV Trust – The development of an extracellular vesicle therapy for brain damage after stroke.

Molecular and chemical cell biology

The elucidation of disease-relevant molecular mechanisms remains the decisive challenge for basic biomedical research in the 21st century despite enormous progress in the field of system-wide data acquisition and the precise manipulation of genetic material. The main area of research in Molecular and Chemical Cell Biology is aiming to shed light on the molecular mechanisms of important biological processes by using modern cell-biological and biochemical methods. The underlying philosophy is that a deep mechanistic understanding of fundamental cellular processes is a prerequisite for understanding pathological changes, identifying targeted innovative approaches to therapies and developing new drugs. This research programme requires a high degree of interdisciplinarity, for which the ZMB offers excellent conditions by combining biology, chemistry and medicine “under one roof”. A core task of this programme is the analysis of cellular signalling pathways and molecular switches (protein complexes) that control the orientation of downstream processes at signalling decision points. A special focus is placed on signalling pathways that control cell proliferation as well as molecular regulation mechanisms of the cell cycle. This work is supported by chemistry, which is developing active substances for acute, selective and titratable intervention in molecular processes and structures.

Selection of current network initiatives

Coordination by UDE/UK Essen

CRC 1093 Supramolecular chemistry on proteins; Profs. Thomas Schrader/Carsten Schmuck (†)

Lipid Divide – Resolving the “lipid divide” by unravelling the evolution and role of fatty acidmetabolic pathways in Archaea, VW-Stiftung; Prof. Bettina Siebers

Participation by UDE/UK Essen

EXC 2033 RESOLV – Ruhr Explores Solvation, PI Prof. Elsa Sanchez-Garcia

Lead Market LifeSciences.NRW Projects

HTRA1 inhibitors – Inhibitors of the serine protease HTRA1 for the treatment of age-related blindness

SYNGOPRO – Synergistic effects of gold nanoparticles and proton radiation in the treatment of childhood brain tumours

The interdisciplinary linkage of the ZMB is also documented by numerous groups that belong to the Centre for Nanointegration (CENIDE), where they have contributed their expertise to the NanoBioMaterials focal point.

Core facilities

The ACE – Analytics Core Facility Essen (head: Prof. Markus Kaiser) provides technologies and methods for protein analytics and the biophysical characterization of proteins and small molecules. The excellent equipment for pro­teomics has been expanded by the acquisition of an additional mass spectrometer with UPLC and HDX sample preparation to meet the demand for mass spectrometry-based methods for the elucidation of structure-activity relationships and the characterization of protein-protein and protein-small molecule interactions.

Structural biology work is performed by including the NMR spectroscopy unit (head: Prof. Peter Bayer) and the ZMB members of the Max Planck Institute for Molecular Physiology, Dortmund, Prof. Stefan Raunser (electron microscopy) and Prof. Andrea Musacchio (X-ray structure analysis). The Genomics & Transcriptomics Facility (GTF) (head: Prof. Ludger Klein-Hitpass until 2019) and the Department of Genome Informatics (head: Prof. Sven Rahmann, Institute of Human Genetics) carry out genome and transcriptome analyses at the UK Essen.

The imaging centres ICCE – Imaging Center Campus Essen (headed by Prof. Hemmo Meyer) and IMCES – Imaging Center Essen (headed by Prof. Matthias Gunzer) have the latest equipment for state-of-the-art imaging. The ICCE is essential for imaging-based detection and live-cell based imaging of spatial and temporal dynamics of subcellular structures. The IMCES has broad expertise in light and electron microscopy, but also offers technical advice on sample preparation as well as support and image analysis for in vivo and intravital imaging procedures. Both facilities have been expanded in the past two years. In 2018, the ICCE was enhanced with a confocal Leica TCS SP8X FALCON laser scanning microscope, which in addition to the traditional high-resolution methods enables the use of time-resolved microscopy techniques such as Fluorescence Lifetime Imaging (FLIM) and Fluorescence Correlation Spectroscopy (FCS). Since 2019, a state-of-the-art light-sheet microscope (a deconvolution light-sheet microscope for mesoscopic tissue imaging) has been available at the IMCES. Funds were secured for both devices from the German Research Foundation (DFG).