Department of Hematology, Oncology and Cancer Immunology
Campus Benjamin Franklin 
Charité - Universitätsmedizin Berlin

Email: francis.baumgartner@charite.de

Project title:
Pathogenesis of ASXL1mutated AML; deciphering mechanisms for novel rational interventions

This project aims to deepen our molecular understanding of ASXL1-mutated (ASXL1mut) acute myeloid leukemia (AML). ASXL1mut frequently occur in myeloid malignancies and, especially in AML, are accompanied by an unfavorable prognosis. By combining Asxl1mut with a genetic system randomly causing mutations, leukemia occurs in mice. After sequencing, Asxl1mut AML are compared to large-scale human ASXL1mut AML datasets, enabling the pinpointing of novel crucial events in leukemogenesis. The most promising identified cancer genes are then (pre)clinically validated for their therapeutic use, e.g., through the development of biomarkers or individualized targeted (combination) therapies.

Laboratory of Tumor heterogeneity and treatment resistance in pediatric cancer
Department of Pediatric Oncology/Hematology at Charité-Universitätsmedizin Berlin
Experimental and Clinical Research Center (ECRC) of the MDC and Charité-Universitätsmedizin Berlin, Germany

E-mail: bartolomeo.bosco@charite.de

Project Title: Unveiling interactions between senescent tumor cells and the host immune system - Implications for Senolytic Immunotherapy

Therapy-induced senescence (TIS) prevents tumor growth and improves treatment outcome in many preclinical cancer models. TIS also alters the tumor biology and environment, contributing to treatment resistance and tumor relapse. There is a close relationship between senescent tumors and the host immune system, but the molecular mechanism of their interaction remains unclear and contingent upon cancer type. Using spatial proteomic, biochemistry and molecular biology techniques, the aim of my project is to characterize the interactions between senescent tumor and the host immune system to identify new actionable moieties to improve the efficacy of senolytic immunotherapies in different cancers.
 

Institute of Pathology, Charité - Universitätsmedizin Berlin

E-Mail: mihnea.dragomir@charite.de

Project Title: Using DNA methylation profiling for differential diagnosis and for determining the origin of ovarian cancers

My research interests lie in classifying, solving differential diagnosis problems, and determining the origin of ovarian cancers. We are using DNA methylation data to develop machine learning algorithms for analyzing ovarian tumors. DNA methylation patterns are highly tissue specific, hence are an ideal method for performing differential diagnosis. Currently, we aim to develop a machine learning classifier that can differentiate subtypes of ovarian carcinomas. Additionally, we aim to use DNA methylation data to predict the outcome of and to subclassify ovarian carcinomas. We plan to expand our research to other female reproductive system tumors.

Department of Radiation Oncology, Charité - Universitätsmedizin Berlin

Email: felix.ehret@charite.de

Project title: The Role of Radiotherapy in the Treatment of Atypical Meningiomas – A Methylome- and Genome-based Analysis.

The role of an adjuvant radiotherapy for grade 2 meningiomas remains unclear. The traditional approach of meningioma diagnosis using only light microscopy and immunohistochemistry to distinguish the current subclasses is prone to interobserver biases and limited regarding personalized treatment decision making. This knowledge gap is highlighted by contradictory findings in various studies. By implementing a DNA-methylation-based classifier and incorporating genetic risk factors to ensure accurate tumor subtype identification, the project aims to specifically assess the role of adjuvant radiotherapy in a homogenous meningioma cohort.
 

Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum
Klinik für Pädiatrie mit Schwerpunkt Onkologie, Hämatologie und Stammzelltransplantation

Email: jonas.grauhan@charite.de

Project Title: Understanding and circumventing resistance to targeted immunotherapy in pediatric relapsed/refractory B-cell precursor acute lymphoblastic leukemia

Targeted immunotherapy, e.g. with the CD19-directed bispecific T-cell engager Blinatumomab or the CD22-directed toxin-conjugated monoclonal antibody Inotuzumab/Ozogamicin, has significantly improved the outcome of patients with pediatric r/r BCP-ALL. However, several resistance mechanisms have been observed. As a prerequisite for circumventing treatment failure, our research module aims at elucidating the underlying intrinsic or acquired resistance mechanisms. Furthermore, we investigate their relevance in clinical subgroups and try to identify predictors of response failure. We thereby hope to improve precision medicine concepts in upcoming clinical trials for pediatric r/r BCP-ALL.

Functional genomics of paediatric cancers group, Experimental and Clinical Research Center (ECRC) of the Max Delbrück Center (MDC) and Charité Berlin, Germany

Postdoctoral Computational Biologist

E-Mail: kerstin.haase@charite.de

Project Title: Functional relevance of DNA circularization and its contribution to genetic heterogeneity and evolution in childhood solid tumours

My work aims to assess changes in extrachromosomal circular DNA (ecDNA) heterogeneity over time using various cell types and sequencing techniques. Insights from these data will help determine how circular DNA elements are selected for and expressed in the context of enhanced proliferation. Understanding the nature and clinical importance of ecDNA is currently limited by our ability to reconstruct entire circles and genomic fragments contained therein. Hence, my project involves adaption and integration of existing methods, as well as development of new algorithms to reliably quantify and reconstruct ecDNA elements from bulk and single-cell sequencing data at clinically relevant time points.

Charité Universitaetsmedizin Berlin

Department Dermatology, Venereology and Allergology

AG Molecular Immunology Charité

Head of Experimental Research

Charitéplatz 1, 10117 Berlin

E-Mail: franz.hilke@charite.de

Project Title: Identification and validation of genetic and cellular biomarkers for patient stratification, prognosis and early detection of resistance mechanisms in the context of tumor therapy.

My research interests lie in understanding and deciphering the molecular mechanisms underlying tumorigenesis and cause targeted and/or immune checkpoint inhibitor therapies to fail. Currently, we focus on biobanking for the purpose of comprehensive genomic tumor characterization and the implementation of liquid biopsy. Second, we study immune adverse events, especially in the skin, during immune checkpoint therapy to understand and compare the underlying molecular mechanism to inflammatory and autoimmune diseases of the skin. Third, we are interested in the different compartments of the immune system fighting cancer, particularly the role of the dendritic cells and the killing by granzymB.

Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie
Campus Virchow-Klinikum
Charité – Universitätsmedizin Berlin

E-Mail: benjamin.locher@charite.de

Project Title: Classical and Therapy-Associated Clonal Hematopoiesis (CH) in Patients With Chronic Lymphocytic Leukemia (CLL)

Clonal hematopoiesis (CH) refers to the presence of mutant blood cell clones, a condition that is prevalent among the elderly population. Its significance extends to various clinical conditions, notably cardiovascular and malignant diseases. My project aims to explore the clinical and mechanistic implications of CH in CLL patients. Besides classical CH genes, I focus on mutations associated with targeted therapies, deciphering the behavior of the hematopoietic system under novel kinds of selection pressure. In addition to sequencing techniques, I employ CRISPR/Cas9 to create mutant CH model systems.

Laboratory of Tumor heterogeneity and treatment resistance in pediatric cancer 
Department of Pediatric Oncology/Hematology at Charité-Universitätsmedizin Berlin 
Experimental and Clinical Research Center (ECRC) of the MDC and Charité-Universitätsmedizin Berlin, Germany 

E-Mail: giulia.montuori@charite.de

Project Title: Extrachromosomal MYCN amplification dynamics enable rapid adaptation to chemotherapy in neuroblastoma

Neuroblastoma commonly affects very young children. Despite their generally positive initial response to treatment, these tumors frequently recur with surprising resistance. This is especially puzzling since neuroblastomas typically show little genetic heterogeneity at diagnosis, pointing to unknown rapid adaptation mechanisms. By utilizing bulk and single-cell sequencing, as well as spatial proteomics analyses, we've found that extrachromosomal DNA (ecDNA)-driven genetic heterogeneity leads to variations in treatment response among cells containing MYCN amplification. This insight may explain why high-risk neuroblastomas can rapidly recur after initial treatment success.

Department of Hematology and Oncology

Charité – Universitätsmedizin Berlin

Berlin

E-Mail: arunima.murgai@charite.de

Protein ubiquitination is a post-translational modification that leads to proteasomal degradation or altered function of a protein. My project aims to investigate the oncogenic role of deubuquitinating enzymes (DUBs) and their exploitation as drug targets in Acute Myeloid Leukemia (AML). Our preliminary CRISPR screenings for DUB inactivation identified USP7 to be essential for several AML cell lines. A combinatorial approach encompassing proteomic, biochemistry and molecular biology analyses will aim to identify novel the substrates of USP7 which are critical for AML. The results of this project will help to further understand the role of the ubiquitin-proteasome system in the pathogenesis of AML and to identify new therapeutic approaches.

Department for Hematology, Oncology and Tumor Immunology

German Cancer Consortium (DKTK), partner site Berlin

Campus Virchow Clinic, Charité Berlin

E-Mail: daniel.noerenberg@charite.de

Project Title: Genetic Characterization of Primary Mediastinal B cell Lymphoma

Unravelling genetic aberrations underlying PMBL lymphomagenesis has the potential to identify new targets for tailored therapy approaches. A thorough description of the mutational spectrum in PMBL and the identification of key oncogenic drivers will thus facilitate rational therapeutic approaches. Until now, we have collected the world’s largest PMBL cohort (n>400) through national and international collaborations comprising clinically well annotated patients. Using a combination of whole-exome, targeted deep resequencing and gene expression analysis, we aim to identify key oncogenic drivers and deregulated signaling pathways in PMBL. Based on the previous molecular analyses, functional consequences of candidate driver mutations will be analyzed in PMBL cell lines using the CRISPR/Cas technology.

(© Charité – Universitätsmedizin Berlin)

Department of Nuclear Medicine

Charité – Universitätsmedizin Berlin

Augustenburger Platz 1, D-13353 Berlin, Germany

E-Mail: julian.rogasch@charite.de

Project Title: Image-derived biomarkers from FDG-PET/CT for staging and prognosis in non-small cell lung cancer

The research aims at improving non-invasive pretherapeutic staging using FDG-PET/CT in patients with non-small cell lung cancer (NSCLC) using image-derived biomarkers (radiomics) and machine learning-based classifiers. A special focus is to improve thoracic lymph node staging. Furthermore, biomarkers are used to develop more differentiated prognostic models to predict patient survival after curatively intended treatment.

(© Charité – Universitätsmedizin Berlin)

Department of Radiation Oncology

Charité – Universitätsmedizin Berlin

 Augustenburger Platz 1, 13353 Berlin

Email: siyer.roohani@charite.de    

Link institutional website
Link Sarkom-Zentrum Charité website

Project title: Breaking Radioresistance of Soft Tissue Sarcomas by New Combination Therapies: Development of a Preclinical Pipeline

Despite their radioresistance and heterogeneity of over 70 subtypes, all soft tissue sarcomas (STS) are treated with the same perioperative radiotherapy regimen. Preclinical and clinical data on effective combination therapies of radiation and targeted compounds is scarce. This proof-of-concept study uses preclinical 3D models of STS to test two hypotheses: 1) Differences in radioresistance among STS subtypes can be reproducibly shown in 3D STS models; 2) New combination therapies of radiation + targeted compounds can overcome radioresistance in STS and be demonstrated in 3D STS models. The study lays the foundation for a preclinical drug and radiation screening platform for STS.

Department of Pediatric Oncology and Hematology
University Hospital: Charité – Universitätsmedizin Berlin

E-Mail: Karin.toews@charite.de

Project Title: Unraveling interplay between MYCN and cellular components in the immunosuppressive high-risk 
neuroblastoma microenvironment to enhance immunotherapy success

Half of high-risk neuroblastomas harbor amplifications of the MYCN oncogene, a key player in progression and metastasis and correlating with poor prognosis in pediatric patients. Chimeric antigen receptor (CAR) T cells offer a new approach against high-risk neuroblastoma. However, tumorassociated macrophages and cancer-associated fibroblasts, contribute with intertwined function to the immunosuppressive microenvironment, thus impeding CAR T cell efficacy. My research aims to uncover how oncogenic MYCN levels influence the presence, behavior, and function of macrophages and fibroblasts in the neuroblastoma microenvironment and how these components in turn hinder CAR T cell success.

Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin
and Max-Delbrück Centrum for Molecular Medicine

E-Mail: Sebastian.Torke@charite.de

Project title:  Characterizing the role of MACC1, a causal driver of cancer metastasis, in immune evasion

Metastasis accounts for >90% of cancer deaths. To improve patient outcomes, identifying (targetable) causal drivers of metastasis is essential. MACC1 acts as such a driver in more than 20 cancer entities. One key prerequisite for metastasis is the evasion of immune responses. Whilst MACC1 is central for many hallmarks of cancer, its effect on immunological processes remains poorly understood. Using spatial proteomics, high-throughput data sets and animal models, we aim to characterize the role of MACC1 in caner immune evasion. Characterizing metastatic potential and anti-tumor immunity will also help to improve the understanding of intervention strategies, specifically immunotherapies.

Berlin Institute of Health, Department for Functional Diagnostics

E-Mail: leonie.stockschlaeder@charite.de

Project title: Exploring Paths of Tumorigenesis through the Characterization of the Human Somatic Mutational Landscape

Wat can we learn about disease from the healthy? To answer this question, in my current research project I focus on the molecular analysis of normal and diseased human tissues. Specifically, we analyze DNA-sequencing data from normal, precancerous, and cancerous tissues to analyze and compare mutational processes in the different stages of tumorigenesis. With this approach we aim to characterize different paths of tumorigenesis and identify yet unknown molecular tissues of origin of different cancer types.

Department of Neurosurgery
German Cancer Consortium (DKTK), partner site Berlin
Campus Mitte Clinic, Charité Universitätsmedizin Berlin

E-Mail: david.wasilewski@charite.de

Project Title: Characterization of the tumor microenvironment, cellular composition and molecular changes in CNS metastases and primary brain tumors of therapy naive and pre-treated patients

The primary objective of our study is to characterize the tumor immune microenvironment (TIME), cellular composition, and molecular changes in brain metastases (BrM). The research aims to understand the interactions between tumor cells and their surrounding environment, especially in patients who have undergone different treatments. The study hypothesizes that the composition of the tumor microenvironment can be altered by prior treatments but on the other hand can also assist predict response to future treatments such immunotherapy. Using scalable and spatial techniques like multiplex immunohistochemistry, MALDI imaging as well as gene expression analyzes the study will analyze tissue samples to identify therapy-associated changes. 

Similarly, the project will employ an established pre-clinical ex vivo model using patient-derived explant cultures, which will facilitate experimental studies to define the functions of individual components of the tumor microenvironment. The ultimate goal is to identify potential resistance mechanisms to treatments and provide insights for future therapeutic strategies.

Charité - Universitätsmedizin Berlin
Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie CCM

E-Mail: soo-ann.yap@charite.de

Project title: SIGN-OC (SIGNature for neoadjuvant chemotherapy in Ovarian Cancer)

The gold standard of care for ovarian cancer consists of chemotherapy and debulking surgery but the debate on optimal treatment sequence is still ongoing. In the phase III AGO-OVAR TRUST trial,746 patients were randomized into two treatment arms, comparing neoadjuvant chemotherapy followed by surgery vs. upfront surgery. Our goal within the SIGN-OC JF program is to analyze clinical samples obtained within the TRUST trial to study mutational signatures and predictive biomarkers of chemotherapy response with a custom designed panel of 232 genes, including frequent alterations in ovarian cancer, with emphasis on HRR- and PI3K/AKT/mTOR pathway associated genes.

Institute of Clinical Artificial Intelligence
Else Kröner Fresenius Center for Digital Health, TU Dresden

E-Mail: JanNiklas.Clusmann@ukdd.de

Project title: Machine learning for risk stratification of liver cancer in real-world data

Hepatocellular carcinoma is a deadly malignancy, often diagnosed at late stages. Current screening is limited to patients with liver cirrhosis, despite a variety of risk factors being characterized. This poses a challenge in risk stratification. The goal of my project is to train machine learning models on real-world data from large-scale biobanks such as the UK Biobank (n=500.000), integrating physical, serum, genomic, and metabolomic data. Models will be built for several, clinically relevant scenarios, comparing added information per data modality. Once the external validation on several other biobanks is performed, the goal is to bring AI-based risk prediction into clinical studies.

Department of Abdominal, Thoracic and Vascular Surgery

University Hospital Dresden, Dresden, Germany

E-mail: Hannah_sophie.muti@tu-dresden.de

Project title: Developing diagnostic and prognostic biomarkers for gastrointestinal cancers with AI-assisted image analysis

Artificial intelligence (AI) can process large amounts of data in a very short time, making it suitable for analyzing complex relationships beyond human capabilities. In precision oncology, this can be utilized to derive biological and prognostic information from oncological imaging data. Gastrointestinal tumors are of particular interest due to their high prevalence and biological heterogeneity. Colon and gastric adenocarcinomas in particular have a high incidence worldwide. Some patients exhibit differences in long-term survival despite similar initial disease stages, which is not tackled in clinical routine. AI has the potential to enhance existing strategies for prognostic stratification of patients with gastrointestinal tumors. In our project, we aim to identify prognostic information in clinical imaging data of colon and gastric adenocarcinoma patients across different time points and disease stages. 

Department of Visceral, Thoracic and Vascular Surgery
Carl Gustav Carus University Hospital Dresden

Email: Carla.portulano@ukdd.de

Project title: Modelling gastric cancer using stomach-specific inducible mouse models and patient 
derived organoids. 

Gastric cancer (GC) is the third leading cause of cancer deaths. Due to missing early clinical signs, GC is diagnosed at late stage cancer with distant metastases, resulting in incurable disease. Therefore, I aim to shed light on the pathological mechanisms of GC metastasis. Additionally, I aim to investigate the tumorigenesis of gastric adenosquamous cancer (ASC) which is characterized by aggressive tumor progression. Since the pathogenesis of ASC is unknown, it is difficult to define treatment strategies.
Therefore, I plan to identify the mutational pattern and transcriptomic profile of ASC. For both projects, I will use stomach-specific mouse models and patient derived organoids.

Department of Hematology, Cellular Therapy and Medical Oncology

University Hospital Carl Gustav Carus Dresden, Dresden

E-Mail: julien.subburayalu@ukdd.de

Project title: Characterization of the antitumoral potential of human genome-modified macrophages

Cancer immunotherapy based on macrophages are hindered by a postmitotic phenotype and a proclivity for repolarization by tumor cells. Chimeric antigen receptor (CAR)-bearing macrophages have recently been shown to effectively eat away at tumor cells. Our work shows that genetic modification in the absence of specific CARs in macrophages maintains antitumoral effects which enables applicability in tumors that have no identifiable CAR target.
Our macrophages are denoted by a continuous expansion of terminally differentiated macrophages in vitro, thus potentially enabling cellular therapy. We are committed to delivering a cell therapy product able to outsmart solid tumors even in instances where conventional therapies have failed.

Else Kroener Fresenius Center for Digital Health, 
Technical University Dresden, Dresden, Germany
and Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

E-Mail: Isabella.wiest@tu-dresden.de

Project title: Beyond Traditional Methods: Leveraging Large Language Models to Unveil Hidden Gems in Oncology Data

The field of oncology heavily relies on the transfer of information between healthcare providers and researchers, a process often hampered by the unstructured nature of medical data. Key insights remain buried within free-text formats, eluding traditional quantitative analysis. Large Language Models (LLMs) present a solution to these longstanding challenges, surpassing classical natural language processing (NLP) techniques in both scope and depth. This project aims to employ LLMs to systematically decode and organize vast amounts of text data, which, due to time-consuming processing requirements, have been underutilized at scale for broader informational gains in oncology. The goal is to enhance oncological data management, facilitating a more scalable and efficient approach for information extraction that supports improvements in diagnosis and treatment strategies.

Department of Human Genetics, University Hospital Essen, University Duisburg-Essen

E-Mail: Nicole.Barwinski@uk-essen.de

Project Title: cf-DNA and EVs as sources for biomarkers for early detection of second primary malignancies in patients with heritable retinoblastoma

Heritable retinoblastoma is a tumour predisposition syndrome caused by heterozygosity for pathogenic RB1 variants. Patients have a high risk to develop a second primary malignancy later in life. Development of such tumours is often initiated by loss of heterozygosity of the RB1 gene. The aim of our project is to develop a noninvasive blood test for the early detection of these secondary cancers. Therefore we investigate cfDNA released by tumour cells to detect the allelic imbalance at the RB1 gene locus. Using the SimSenSeq technology (Ståhlberg et al. 2017) we perform Next-Generation Sequencing to determine the allelic ratio with high sensitivity and specificity to reach the requirements of a diagnostic test.

DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ)

DKTK partner site Essen/Düsseldorf

Universitätsklinikum Essen
Hufelandstrasse 55, 45147 Essen

E-Mail: c.dobersalske@dkfz.de

Project Title: Tumor microenvironment and resistance mechanisms in malignant glioma

The dynamic and heterogenous cell composition in the tumor microenvironment (TME) actively influences therapeutic efficacy in all different kinds of tumor entities. Our aim is to unravel the insufficiently characterized TME in glioma by establishing models that are acutely maintain the TME of clinical specimen. We firmly believe that understanding and further targeting microenvironmental factors is indispensable to allow the identification of appropriate treatment strategies and to potentially overcome therapy resistance.

Clinic for Internal Medicine (Tumor Research)

DKTK partner site Essen/Düsseldorf

Essen University Hospital

Hufelandstrasse 55

45147 Essen

E-Mail: ilektraantonia.mavroeidi@uk-essen.de

Project Title: Translational theranostic applications in oncology

Theranostics stands as a cornerstone of personalized medicine, meticulously delving into specific target structures within tumors or their microenvironment to enable both diagnostic and therapeutic interventions. Within this cutting-edge domain, radiotheranostics integrates molecular imaging with targeted radionuclide therapy, offering an opportunity to selectively target and eliminate tumor cells while minimizing adverse effects. This approach holds promise for highly effective therapies with reduced toxicity, addressing concerns related to resistance.

My research primarily focuses on translational theranostic projects in a multidisciplinary and and comprehensive manner.  On the one hand, i work on unravelling the intricate dynamics among FAP-expressing cells within tumors, cancer-associated fibroblasts (CAFs), and tumor cells, along with their interactions within the tumor microenvironment. This translational effort initially targets sarcomas, with the aim of extending to other tumor entities.  Additionally, I aim to elucidate the role of SSTR2 in SCLC, investigating its correlation with immunohistochemistry and its impact on patient survival, with the utmost purpose of detecting patients eligible for theranostic approaches.  

Neutrophil Biology and Translational Oncology Group, ENT department
Universitätsklinikum Essen
Hufelandstrasse 55
45147 Essen

E-Mail: ekaterina.pylaeva@uk-essen.de

Project Title: Therapeutic modulation of glycosaminoglycan-chemokine interactions in cancer

Despite the significant success of the existing anticancer treatment options, the overall survival in various cancer types remains poor. One of the reasons of inefficiency of anticancer treatment is develpment of tumor resistance. It is partially mediated by expansion of exhausted and/or immunosuppressive immune cells in the tumor tissue and lymph nodes, which suppress the cytotoxic mechanisms and support the survival and metastasis.

Tumor microenvironment (soluble factors and cellular interactions) drive newly migrated immune cells into exhausted and/or immunosuppressive state. Glycosaminoglycans on endothelium and extracellular matrix bind the chemoattractants and provide the stable concentration gradient important for migration and activation of immune cells.
With this project, we aim to restore anti-tumor adaptive immune responses by targeting glycosaminoglycan-chemokine interactions.

Department of Medical Oncology, West German Cancer Center, University Hospital Essen
Bridge Institute of Experimental Tumor Therapy (BIT) and Division of Solid Tumor Translational Oncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Partner Site University Hospital Essen

E-Mail: hendrik.schuermann@uk-essen.de

Project Title: Cellular plasticity in pancreatic cancer – from phenotypical organoid screening to underlying biophysical mechanisms

Pancreatic cancer is notorious for its poor survival rates and remarkable resistance to available therapies. Early-passaged patient-derived tumor organoids (PDO) recapitulate tumor heterogeneity and have the potential for in vitro response prediction. However, widely utilized assays do not capture spatial heterogeneity and dynamics.

My research project focuses on temporally resolved, 3D imaging-based drug screenings of pancreatic cancer organoids to detect and characterize phenotypical and programmed cell death-related drug responses. Our aim is to incorporate these features to predict patient response in vitro and identify potential drug combinations to exploit cell state vulnerabilities. This translational project is complemented by a mechanistic project to study the role of collective cell mechanics in distinct phenotypes and clinical aggressiveness. 

By integrating spatiotemporal information with mechanical properties, we hope to contribute to the utilization of PDO for clinical decision-making.

MSNZ Research Fellow I Medical Scientist

Institute of Neuroradiology
Research Group “Translational Oncology”
University Hospital Frankfurt

E-Mail: seyma.alcicek@kgu.de 

Research Focus: Non-invasive Imaging of Tumor Metabolism Using In vivo Magnetic Resonance Spectroscopy 

Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive technique that enables in vivo observation of tissue metabolism by exploiting the magnetic properties of cell metabolites. My research focuses on improving this methodology and its postprocessing methods to monitor altered cellular metabolism, the hallmark of cancer. MRSI provides the unique opportunity to collect metabolic fingerprints of tumor manifestations in vivo in patients with the ultimate goal of identifying markers for therapy stratification and monitoring.

III Medical Clinic and Polyclinic

University Medical Center of Johannes Gutenberg University Mainz

E-Mail: dolgikna@uni-mainz.de

Project Title: Mechanisms of non-genetic resistance to Menin inhibitors in NPM1 mutant AML

The interaction between MLL1 and Menin proteins plays a crucial role in acute myeloid leukemias (AMLs) with MLL translocations (MLLr) or NPM1 mutations. Menin inhibitors disrupt this interaction, leading to reduced expression of leukemic genes and inducing differentiation in MLLr and NPM1mut AML. However, single-drug treatments often face limitations due to the development of drug resistance. To address this issue, we aimed to understand the molecular mechanisms underlying sensitivity and resistance to Menin-MLL1 inhibition in order to provide potential avenues for a promising and novel AML treatment.

Department of Hematology/Medical Oncology

University Hospital Frankfurt, Germany

E-Mail: julius.enssle@kgu.de

Project Title: Functional proteogenomic characterization of mantle cell lymphoma

Our research aims at expanding the characterization of mantle cell lymphoma (MCL) by mass spectrometry quantitative proteome profiling of primary MCL samples together with whole-exome sequencing, transcriptome sequencing data and clinical outcome data to obtain a multilevel proteogenomic dataset. By bioinformatic integration, we aim at identifying proteogenomic clusters with prognostic relevance and gain insight into the underlying biologic processes. Additionally, analysis of genetic vulnerabilities will allow functional validation of these findings and evaluation of potential biomarkers and novel therapeutic targets to translate the results into novel clinical trials in MCL.

Department of Otorhinolaryngology

University Hospital Frankfurt/Main

Theodor-Stern-Kai 7; Haus 8D, 60590 Frankfurt am Main

E-Mail: christian.issing@kgu.de

Project Title: “Patient-derived tumor organoids from head and neck squamous cell carcinoma as a co-clinical research platform”

Head and neck squamous cell carcinoma (HNSCC) are among the most common malignant neoplasms worldwide. While locally limited disease can be cured by surgery and/or radiochemotherapy, a multimodal and potentially side-effect rich therapy regimen is required for advanced HNSCC. The genetic heterogeneity and distinct aetiologies of HNSCC significantly complicates the therapy and makes an individualized therapeutic approach indispensable for a promising long-term treatment. Patient-derived tumor organoids (PDTOs) could provide a                                                                       preclinincal model to test treatment responses in vitro.

Élément Christian20Issing.jpg image

University Cancer Center (UCT), University Medical Center (UMC) of the Johannes Gutenberg University and German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Germany Center for Thrombosis and Hemostasis (CTH), Institute for Clinical Chemistry and Laboratory Medicine

E-Mail: Essak.Khan@unimedizin-mainz.de

Project Title: Disentangling tumor tissue specific regulatory mechanisms of prothrombin (proF2) gene expression by differential high-content screening in an integrated genetic reporter system

In this project, we are interested in developing a standardized methodology for systematically dissecting the tumor-specific disease entities and mechanism that promote extrahepatic proF2 involved in cancer progression using  a transgenic reporter mouse model (Nourse et al., 2021). In a proof of concept, the suitability of this experimental setup to perceive hitherto unknown sources of detrimental extrahepatic proF2 has been  confirmed (Nourse et al., 2021) which corresponds to findings from tumor patients (Xue et al., 2010). A broad direct in vivo RNAi screening (Wuestefeld et al., 2013) and counter validation in human patient’s samples is expected to unravel novel insights into disease relevant entities and pave the way for developing new therapeutic concepts.

Department of Urology

University Hospital Frankfurt

Frankfurt, Germany

E-Mail: Florestanjohannes.koll@kgu.de

Porject Title: Molecular and histological subtyping of muscle-invasive bladder cancer

Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease with poor oncologic outcome. Six different molecular subtypes of bladder cancer have been identified by transcriptomic profiling. These classes differ regarding underlying oncogenic mechanisms, histology and clinical characteristics, including outcomes. But so far, no clinical translation and application of molecular subtypes has occurred. We aim to validate a robust method to define molecular subtypes in MIBC and to correlate these with histological subtypes, response to chemotherapy and survival-rates.

University Cancer Center (UCT), University Medical Center (UMC) of the Johannes Gutenberg University and German Cancer Consortium (DKTK)

Partner Site Frankfurt/Mainz, Germany Department of Internal Medicine III (Hematology, Oncology, Pneumology)

E-Mail: korbinian.kropp@unimedizin-mainz.de

Project Title: Targeted knock-in of an HLA-independent, TRP2-specific (chimerized) T-cell receptor using CRISPR/Cas9 and homology-directed repair templates.

In this project, we investigate a novel approach to the generation of transgenic T cells based on the genome-editing platform CRISPR/Cas9. Following the methods of Eyquem et al. (Nature 2017, 543:113-117) and Roth et al. (Nature 2018, 559:405-409) we place tumor-reactive TCRs at the endogenous TCR locus thereby knocking out endogenous TCR expression in a one-step knockout/knock-in approach. This enhances expression of transferred TCRs, minimizes mispairing and thus may ultimately improve safety of patients in potential future translational approaches. In particular, we redirect T cells against melanoma by knock-in of an HLA-independent TRP2-specific TCR.

Rieger Lab
Department of Medicine II, Hematology/Oncology
Goethe University Hospital Frankfurt

Email: marius.kuelp@em.uni-frankfurt.de

Project Title: Synonymous mutations driving clonal hematopoiesis in the context of cardiovascular and malignant diseases

Hematopoietic stem cells acquire somatic mutations in distinct driver genes leading to clonal hematopoiesis (CH), a state which frequently fades to hematologic malignancy. Besides, several studies revealed association of CH with chronic heart failure. Importantly, this was only investigated for amino acid-affecting mutations while synonymous mutations have been completely neglected despite their potential to alter RNA folding, stability, splicing or translational speed and pausing. Therefore, the primary objective of the project is the mechanistic elucidation of how synonymous mutations drive CH and subsequently cause cardiovascular and malignant diseases.
 

Department of Hematology and Oncology, University Medical Center, Johannes Gutenberg University, Mainz, Germany

E-Mail: johrausc@uni-mainz.de

Project Title: Targeting chromatin complexes to reverse AML immune escape for engineered cellular therapy

Our research focuses on the menin-MLL1 interaction, an epigenetic dependency in NPM1 mutated and MLL-rearranged leukemia. Menin-inhibitors have demonstrated promising in vitro and in vivo activity and are currently investigated in clinical trials. While immunotherapy has revolutionized the treatment of solid tumors and lymphatic neoplasms, it has been far less successful against AML. We are investigating if the use of selective epigenetic drugs like menin-inhibitors can augment the efficacy of immunotherapies in AML.

University Cancer Center (UCT), University Medical Center (UMC) of the Johannes Gutenberg University and German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Germany Department of Internal Medicine III (Hematology, Oncology, Pneumology)

E-Mail: viral.shah@uni-mainz.de

Project Title: Enhancing PARP inhibition mediated DNA Damage and leveraging inherent anti-apoptotic dependencies in acute myeloid leukemia

Acute myeloid leukemia (AML) is characterized by increased proliferation, evasion of apoptotic stimuli, and block of differentiation.In this project, we aim at shedding light on mechanisms involved in maintaining genomic stability, exploring pathways regulating DSB repair and exploit mechanisms that prevent induction of apoptosis in highly proliferating AML cells.

Dr. Senckenberg Institute of Neurooncology

University Hospital Frankfurt/Main

E-Mail: pia.zeiner@kgu.de

Project Title: Interaction between glioma-associated microglia/macrophages and tumor cells in the context of targeted cancer therapies and immunotherapies

Short description: Our research is focusing on the investigation of the immunological response in the microenvironment of brain tumors with a special focus on glioma-associated microglia and macrophages (GAMs). In particular, we assess the influence of established and novel targeted therapies on GAM functions and the potential impact on therapeutic response in glioblastoma patients. One aim of the study is the detailed characterization of the mTOR-signalling cascade as a central regulator and potential therapeutic target in GAMs. 

Department of Urology

Medical Center-University of Freiburg, DKTK partner site, Germany

E-mail: jatin.bedi@uniklinik-freiburg.de

Project Title: Investigating the consequences and therapeutic vulnerabilities of KDM6A and KDM6C mutations in Urothelial carcinoma

KDM6A and KDM6C, tumor suppressor genes on the X and Y chromosomes, are frequently inactivated in male bladder cancer. This project investigates their roles in bladder carcinogenesis. KDM6A often undergoes inactivating mutations, while KDM6C is inactivated through Y chromosome loss. These genes will be knocked in bladder cancer cells, followed by phenotypic assessment including proliferation, migration, invasion, as well as changes in chromatin modifications and protein interactions. Finally, utilizing chemical screening, we will identify synthetic lethalities with 
gene loss, in hope of elucidation their role for potential therapies.

Division of Radiopharmaceutical Development

German Cancer Consortium (DKTK), Partner Site Freiburg

Department of Nuclear Medicine

University Medical Center

Freiburg, Germany

Head of Biotechnological Development and Preclinical Imaging

Project Title: Development and translation of novel theranostic hybrid molecules for pre-, intra-, and postoperative diagnosis and therapy of cancer

Our research is focusing on identifying new biomarkers for the classification of tumors, assessing metastasizing potential and monitoring therapy. In particular my group is working on the development of small molecule peptides with a strong focus on hybrid molecules suitable for preoperative imaging, intraoperative navigation as well as for targeted endoradiotherapy of different cancer types. Therefore, we are using innovative biological, biotechnological and chemical approaches to identify novel peptides to a variety of clinically relevant target structures. Our development pipeline comprises the identification of potential binders, their detailed preclinical characterization including imaging studies finally leading to clinical translation.

Institute for Surgical Pathology

University Medical Center Freiburg

E-Mail: matthias.fahrner@uniklinik-freiburg.de

Project Title: In-depth proteogenomics of solid tumors to expand and complement routine molecular diagnostics and support personalized therapeutical strategies

Proteogenomics describes the integration of proteomics to multi-omics studies that integrate DNARNA-, and protein-level omics-data. In my research I apply in-depth proteogenomics on solid tumors
to address two different aspects:

a) Corroboration of determined sequence variants (DNA or RNA-level) on the proteome level; an approach which may also yield information on the proteomic penetrance of said variants. Results may aid in prioritization of potential treatment schemes if there is co-occurrence of multiple variants with clinical implications.

b) Determine the impact of genomic aberrations on oncogenic signaling pathways; many genomic aberrations are linked to oncogenic signaling and proteomic approaches enable corroborative, direct probing of this impact.

Institute of Surgical Pathology
University Medical Center Freiburg
E-Mail: melanie.foell@uniklinik-freiburg.de
Group Website

Project title: Spatially resolved metabolomics and proteomics of solid tumors
My junior research group “MALDI imaging” investigates tumor tissue cohorts and organotypic tissue slice cultures by MALDI mass spectrometry imaging and complementary omics and imaging modalities. MALDI imaging derives hundreds of molecular distribution maps directly from thin tissue slices. We apply MALDI imaging of metabolites and peptides to investigate spatially resolved tumor biology and to derive spatio-molecular signatures with diagnostic and prognostic potential. Furthermore, we establish open-source analysis tools and workflows in the Galaxy platform and work towards standardization and reproducibility of MALDI imaging, which lays the foundation for future clinical applications.

Department of Thoracic Surgery – Division of Cancer Research, University

Medical Center Freiburg
German Cancer Consortium (DKTK), Partner Site Freiburg
Breisacher Str. 115, 79106 Freiburg i.Br.

E-Mail: avantika.ghosh@dkfz-heidelberg.de

Project Titel: Systematic analysis of nonstop extension mutations in high throughput

Research in our group has shown that nonstop mutations are associated with cancer and are known to have a functional impact on protein expression and function. Our group has created the database NonStopDB, a comprehensive set of nonstop mutations in human cancer. In this project we aim to systematically analyse the functional impact of all non-stop extension mutations found somatically in human cancer in a pooled format using reporters and next generation sequencing. 

Department of Urology

Medical Center-University of Freiburg, DKTK partner site, Germany

Email: ezgi.oezyerli.goeknar@uniklinik-freiburg.de

Project title: Deciphering Menin-MLL inhibitors to better target MLL/KMT2A-rearranged leukemia via combinatorial genetic and epigenetic targeting approaches

Targeting protein-protein interactions (PPIs) with small-molecule inhibitors has become a hotbed of modern drug development. In this project, we investigate effect of PPI inhibitors that block Menin from binding to MLL proteins. Menin acts as an essential cofactor for MLL/KMT2A-rearranged leukemia. Menin-MLL inhibitors have recently entered phase I/II clinical trials for treating MLL/KMT2A translocated or NPM1 mutant leukemia. Understanding the complete mechanism of action of Menin-MLL inhibitors as well as developing novel epigenetic/ genetic combinatorial treatment strategies to better eradicate MLL-rearranged leukemia are main objectives of the project. 
 

Department of Hematology, Oncology, and Stem Cell Transplantation

University Medical Center Freiburg

Project Title: Impact of CD30-mediated immune response in T-cell-lymphomas

The aim of this project is to get a better understanding of CD30-axis in disease progression in ALK-induced T-cell lymphomas with focus on immune response, immune escape mechanisms like immunoediting, involved pathways and other immune evasion mechanisms.

Experimental Immunology

University Zürich, Switzerland

Project Title: The immune environment of acute myeloid leukemia

Acute myeloid leukemia (AML) is the most common hematologic malignancy in adults. It is characterized by poor outcome with an overall 5-year-survival of only 50% in young patients and 20% in elderly patients. As the curative potential of allogeneic hematopoietic stem cell transplantation is dependent on immunotherapeutic effects (graft-versus-leukemia effects), immune evasion seems to play a pivotal role in the pathogenesis of AML. A comprehensive research program using highdimensional single cell cytometry combined with bioinformatic analyses represents a powerful tool to gain deep and unbiased insights into the immune signatures of AML patients. Immune patterns that predict response may be integrated into the stratification of AML, particularly in the absence of predictive genetic markers. To verify the impact of the identified signatures, detailed functional analyses of patient mononuclear cells will be performed in vitro to investigate the effect of cell-intrinsic and -extrinsic alterations on anti-AML immunity. The ultimate goal is to identify novel stratifying biomarkers and/or therapeutic targets to overcome immune evasion of AML cells and achieve improved patient outcome.

Department of Thoracic Surgery – Division of Cancer Research, University Medical Center Freiburg

German Cancer Consortium (DKTK), Partner Site Freiburg

Breisacherstr. 115, 79106 Freiburg i.Br.

E-Mail: carla.schmidt@dkfz-heidelberg.de

Project Title: Discovering non-canonical driver mutations in cancer in high-throughput using endogenous models

Most point mutations found in cancer are functionally uncharacterized and hence cannot be exploited for patient stratification and therapy decisions. Current approaches to study mutations endogenously are time-consuming and lack the possibility for high-throughput. In this project, we focus on the introduction of comprehensive libraries of targeted mutations endogenously into the cell genome using innovative CRISPR-derived tools to assess their functional impact and their impact on therapy response and resistance.

Institut für Medizinische Bioinformatik und Systemmedizin

Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg

Arbeitsgruppe Boerries für Systembiologie und Systemmedizin am DKFZ Partnerstandort Freiburg - DKTK

Institut für Molekulare Medizin und Zellforschung, Albert-Ludwigs-Universität Freiburg

Project Title: Genotypic and phenotypic characterization of patient-derived melanoma cell lines

Based on a transcriptome analysis, the aim of this project is to characterize the phenotypic properties of the four individual malignant melanoma cell lines, such as cell survival, proliferation, migration, and invasion. Furthermore, we are studying the underlying mechanisms, which effectuate the phenotype of the melanoma cell lines. Therein, we mainly focus on the MAPK/ERK or PI3K pathways, components of which are frequently mutated and thus are often constitutively active in cancer cells, driving their development and enhanced survival.

Project Title: Identification of early detection markers in pancreatic ductal adenocarcinoma (PDAC)

The aim of this project is to establish an early genetic classifier of PDAC based on a meta-analysis of independent studies. In combination with system biology and bioinformatics approaches, it is our aim to identify early markers of PDAC in patient-derived samples (eg. liquid biopsies). This may allow the differentiation of PDAC from early pancreatic intraepithelial neoplasia (PanIN), pancreatitis, and healthy tissues. In a parallel approach, we seek to inactivate the classifier genes in established PDAC cell lines and to assess the effects of the inactivation on the functionality of these cells.

Department of Radiation Oncology, University Hospital Heidelberg

E-mail: fabian.allmendinger@med.uni-heidelberg.de

Project title: Preclinical model organisms to predict personalized radiation treatment for central nervous system cancer

Patient-derived in vitro models present a promising platform to predict the efficacy of different radiation modalities, including types and dosages, thus promoting personalized treatment planning in radiation oncology. Our aim is to tailor radiation treatment to the preserved tumor biology of individual patients, making it amenable to in-depth analyses. This approach may improve our molecular understanding of how radiation affects brain cancer cells through a comprehensive multi-omic approach and ultimately improve radiation effectiveness while mitigating side effects by optimizing radiation protocols.

Department of Radiation Oncology, University Hospital Heidelberg
Heidelberg Institute of Radiation Oncology (HIRO)
Heidelberg, Germany
E-Mail: Maximilian.deng@med.uni-heidelberg.de
Twitter: @maxiydeng1994

Project title: Molecularly-guided precision radiotherapy in patients with central nervous system tumors
The 2021 update of the WHO classification of central nervous system tumors has integrated comprehensive molecular findings into the diagnostic workflow, enabling a more accurate diagnostic process and risk assessment. Novel radiotherapeutic modalities using protons or carbon ions represent an auspicious therapeutic concept with an increased accuracy in dose delivery - while reducing the radiation dose for the surrounding organs at risk. Post-hoc integrated molecular-morphological scoring will identify patients at risk of progression, where proton- or carbon ion radiotherapy may be particularly beneficial, facilitating the path to a molecularly-guided treatment in patients with brain tumors.

Department of Neurology, University Medical Center Mannheim, Heidelberg University

CCU Neuroimmunology and Brain Tumor Immunology (Prof. Dr. Michael Platten), German Cancer Research Center

Heidelberg, Germany

E-Mail: niklas.grassl@dkfz-heidelberg.de

Project title: Neural stem cell ablation and gliomagenesis – towards a more natural glioma model in mice

Early evolution of primary central nervous system tumors is incompletely understood. In this research project I develop a mouse model that aims to fuel giomagenesis by an ablation of neural stem cells. Thus I hope to recapitulate the natural disease course more accurately with implications for our understanding of gliomagenesis and testing of therapies for CNS tumors.

National Center for Tumor Diseases (NCT)

Department of Medical Oncology and German Cancer Research Center (DKFZ)

Signaling and Functional Genomics (Prof. Dr. Michael Boutros)

Heidelberg, Germany

E-Mail: a.schubert@dkfz.de

Twitter @_A_Schubert

Project Title: Novel strategies to analyze the role of Wnt-signaling in cancer

Deciphering the crosstalk of tumor cells and their surrounding stroma during cancer progression and metastasis is of highest importance to further optimize therapeutic strategies and prevent late recurrence. Wnt signaling governs cell faith and tissue polarity during development and aging. It was found dysregulated in various pathological processes and diseases such as cancer. This project aims to get further mechanistic insights into the complex Wnt-signaling networks using genome engineering and advanced imaging techniques that could lead to the identification of targets for earlier diagnostics and therapeutic intervention.

Division of Stem Cells and Cancer (A010, Prof. Andreas Trumpp)

German Cancer Research Center (DKFZ)

Foundation under Public Law

Im Neuenheimer Feld 280, 69120 Heidelberg

E-Mail: r.wuerth@dkfz.de 

https://www.dkfz.de/en/stammzellen-und-krebs/mitarbeiter.html

https://www.researchgate.net/profile/Roberto_Wuerth 

https://www.linkedin.com/in/wuerth/ 

ORCID: 0000-0002-8156-6756

Project Title: A liquid biopsies platform to study metastasis and to reveal individualized resistance mechanisms in breast cancer patient

Experimentelle Leukämie- und Lymphom-Forschung (ELLF), Medizinische Klinik und Poliklinik III, Klinikum der Universität München, Munich

Pathogenesis of acute leukemia - AG Prof. Dr. med. Philipp Greif 
Medizinische Klinik und Poliklinik III | Arbeitsgruppen (lmu-klinikum.de)

Email: Vanessa.Arfelli@med.uni-muenchen.de

Project Title: Alterations of fatty acid metabolism and pharmacological counteraction in ZBTB7A deficient leukemia

ZBTB7A is a transcription factor frequently mutated in acute myeloid leukemia (AML) patients with t(8;21) translocation (which results in the RUNX1-RUNX1T1 fusion protein). We use CRISPR-Cas9 to knockout ZBTB7A and mimic these loss-of-function mutations in order to study ZBTB7A effect in metabolism. Our ultimate goal is to find metabolic drug targets for therapy. For that, we perform metabolic tracing by mass spec, metabolic flux assays, and treatment with several metabolic inhibitors. Besides, since ZBTB7A prevents RUNX1-RUNX1T1-mediated clonal expansion in vitro, we are interested in investigating the cooperation of ZBTB7A knockout and RUNX1-RUNX1T1 during leukemogenesis in a mouse model. 

Department of Gastroenterology, Technical University Hospital, Munich

E-Mail: Melissa.Barroux@mri.tum.de

Project Title: Tumour evolution and immune microenvironment dynamics in response to neoadjuvant treatment in oesophagael adenocarcinoma

Patients with locally advanced oesophageal cancer (OAC) are treated with surgical resection and neoadjuvant chemotherapy or radiochemotherapy. However, 50% to 60% of tumours are resistant to neoadjuvant therapy, leading to an overall poor outcome with a 5-year survival of 12.6%. The ecological and evolutionary dynamics responsible for treatment failure are incompletely understood. In my research I perform a multi-omics study (whole exome sequencing, RNA-sequencing, T-cell receptor sequencing and image mass cytometry)  with a multi-timepoint strategy to examine treatment response at clonal resolution and to investigate genetic and transcriptomic changes induced by neoadjuvant therapy in OAC patients. This project will provide fundamental insights into clonal dynamics, transcriptomic changes and dynamics of the microenvironment in response to neoadjuvant treatment in OAC patients, in order to provide fundamental insights into treatment response on the molecular level.

Department of Internal Medicine III
LMU Klinikum

Cancer- and Immunometabolism Research Group (CIM)
Genzentrum LMU

E-Mail: maximilian.funk@med.uni-muenchen.de

Project title: Metabolic features of high-risk multiple myeloma

The risk of progression and the response to therapy in multiple myeloma are determined by genomic risk factors including deletion of the tumor suppressor p53. Importantly, p53 is known to profoundly impact cellular metabolism. In our project, we will characterize the metabolic landscape of high-risk myeloma in cell line models and primary patient samples through metabolomic analyzes. We furthermore aim to identify underlying mechanisms and metabolite mediated effects on the tumor environment by employing transcriptomic technologies and functional assays. Ultimately our goal is to identify resistance mechanisms to established drugs and to discover novel therapeutic targets in multiple myeloma.

Kinderklinik München Schwabing

- Klinik und Poliklinik für Kinder- und Jugendmedizin, Klinikum Schwabing, München Klinik gGmbH und Klinikum Rechts der Isar (AöR) der Technischen Universität München -

Phone: 089/3068 2367
Email: hendrik.gassmann@tum.de

Project Title: Identification of tumor-antigen specific T cell receptors for the treatment of
pediatric cancers.

Despite significant survival improvements, cancer ranges among the leading causes of deaths in children and young adults. Immunotherapy including adoptive T cell transfer emerges as promising therapeutic strategy in pediatric hematological and solid malignancies. 
The short- and mid-term goals of the project are to identify and characterize T cell receptors (TCRs) in vitro and in preclinical models targeting overexpressed and shared antigens in pediatric cancers. The aim is to provide data for efficacy and safety of selected TCRs for further evaluation in phase I clinical trials.

LMU Klinikum
Arbeitsgruppe Immunpharmakologie
Abteilung für Klinische Pharmakologie
Medizinische Klinik und Poliklinik III

E-Mail: adrian.Gottschlich@med.uni-muenchen.de

Project Title: Spatial transcriptomic-based dissection of tumor-infiltrating
lymphocytes (TIL) for the improvement of immunotherapies and cellular therapies in pancreatic cancer

The field of artificial intelligence is rapidly expanding, providing novel insights into tumor biology. Single-cell RNA-sequencing (scRNA-Seq) for example can provide information of cell-to-cell interactions at an unforeseen resolution. However, one fundamental limitation of scRNA-seq is the loss of spatial information, which is known to influence prognosis and treatment response of certain cancers. Building on our previous successful investigations, we hypothesize that we can leverage spatially-resolved gene expression profiling to identify pivotal signaling pathways in tumor-infiltrating lymphocytes (TIL) and exploit these pathways for engineering of next-generation cellular therapies.

Klinikum der Universität München, Munich
Experimentelle Leukämie- und Lymphom-Forschung (ELLF), Medizinische Klinik und Poliklinik III

E-Mail: William.Keay@med.uni-muenchen.de

Project title: Functional characterization of recurrent co-occurring gene mutations in follicular lymphoma (FL)

My project focuses on studying co-occurring mutations in FL, using an innovative, fully human ex vivo model system of primary, genetically editable FL-like germinal center B cells. We study different mutations including epigenetic modifiers in the context of autologous immune cells in an organoid-like setting. We hope to gain insights in the heterogenous biology of FL, allowing us to pinpoint altered cellular signalling cascades that can be therapeutically targeted.

Working Group Personalized Radiobiology
Department of Radiation Oncology at the University Hospital rechts der Isar
Technical University of Munich

E-Mail: christopher.kessler@tum.de

Project Title: OXPHOS-Dependent Radiosensitization of Patient-Derived Pancreatic Cancer Organoids

Pancreatic ductal adenocarcinoma is a highly lethal entity with poor prognosis. Neoadjuvant chemoradiotherapy aims to achieve resectability, but intrinsic radioresistance and hypoxia hinder therapeutical success. This project investigates whether inhibiting oxidative phosphorylation (OXPHOS) can enhance radiosensitivity by increasing intracellular oxygen levels. For a translational approach we are using patient-derived organoids, to assess the efficacy of OXPHOS inhibitors combined with radiation. We employ a range of techniques, including immunohistochemistry, cell viability assays, 3D fluorescence microscopy and RNA sequencing to characterize radiation response.

Department of Otorhinolaryngology, Head and Neck Surgery
LMU Klinikum
Munich, German

E-Mail: susanne.flach@med.uni-muenchen.de

Project Title: Personalized circulating cell-free tumour DNA (ctDNA) analysis for detection of molecular residual disease and monitoring of recurrence in patients with head and neck squamous cell carcinoma; Characterization of tumour evolution in the upper aerodigestive tract

Despite evolving therapy regimens, patients with head and neck squamous cell carcinoma (HNSCC) frequently develop recurrences and/or second primary tumours in the upper aerodigestive tract. I am particularly interested in the identification of molecular markers, the use of ctDNA for detection of molecular residual disease and monitoring of recurrence in HNSCC as well as understanding the biological evolution from precancerous lesions to invasive carcinomas in the upper aerodigestive tract (field cancerization) using minimally invasive biopsies.

Surgical resident at the Department of the Allgemein-, Viszeral- und Transplantationschirurgie

Ludwigs-Maximilians-University Munich

E-Mail: Mathilda.Knoblauch@med.uni-muenchen.de

Project Title: The effect of catecholamines and ß-ARs on the invasiveness of colorectal cancer cell

Tumor cell migration and invasion are multifactorially conditioned and the cause for metastasis development. Currently, it is poorly understood how and when cancer cells cross the endothelial barrier and proceed to metastasis. I focus on the aspect of the nervous system on several gastrointestinal and mesenchymal solid tumor entities in vitro and in vivo. My work deals with the influence of the nervous system in colorectal cancer metastasis and possible mechanisms in metastatic organotropism.

Klinikum rechts der Isar
University Hospital of the Technical University Munich
Division of Translational Gastrointestinal Immunology 
Munich

E-Mail: Enric.redondo@tum.de

Project Title: Understanding the adaptation of mucosal-associated invariant T (MAIT) cells to tissues to harness their cell therapeutic potential

Mucosal-associated Innate T (MAIT) cells are highly enriched in healthy liver but depleted in hepatocellular carcinoma (HCC), which prevents them from executing their potential antitumor functions. My research aims to elucidate how MAIT cells are routed towards tissues and which factors determine their adaptation to tissue microenvironments. Understanding the factors contributing to a tissue-resident MAIT cell phenotype could lead to an improvement in their anti-cancer functions. Moreover, I am interested in establishing MAIT-based cell therapies against solid tumors by taking advantage of their innate-like tumor killing capabilities and absence of HLA restriction.

Technical University of Munich
Klinik und Poliklinik für Innere Medizin II

E-Mail: martin.trossbach@tum.de

Project Title: DKTK Organoid Platform; Droplet Microfluidics for PDO Culture

In Prof. Reichert’s group I am co-coordinating the establishment of the DKTK Organoid Platform with its first two use cases, NeoMatch and MetPredict. Both are prospective multicenter pilot trials: NeoMatch aims to  confirm  the  ability  of  pancreatic  cancer  patient-derived  organoids  (PDOs)  in  forecasting response to neoadjuvant chemotherapy, and MetPredict the ability of colorectal cancer liver metastasis patient-derived organoids (CRC LM PDOs) in forecasting liver metastasis recurrence, respectively. Additionally, I am building a microfluidic workflow and aim to demonstrate its effectiveness in improving our current pipeline for generating PDOs of pancreatic ductal adenocarcinoma. Ultimately, this work will result in a better understanding of tumor heterogeneity and plasticity, as well as the interplay with the tumor microenvironment – major obstacles in successful treatment of PDAC, which to this day has a low 5-year-survival rate, despite our best efforts and recent advances. Moreover, breakthroughs relating to PDO model systems would most certainly be translatable to precision medicine applications with an even more direct impact on patients.

Department of Otorhinolaryngology - Head and Neck Surgery & Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.

E-Mail: Bernd.Uhl@med.uni-muenchen.de

Project Title:  Characterization of myeloid leukocyte trafficking for novel therapeutic targets in cancer

The immune system protects the organism from infections, but also from the development of malignant tumors. Adaptive immune cells are well-known to control tumor initiation, progression, and metastasis formation in various cancer entities. During the last years, myeloid immune cells have additionally been recognized as essential players in these processes. The mechanisms underlying the trafficking of these immune cells to malignant lesions, however, remain largely unclear. Hence, the aim of our translational project is to characterize the mechanisms of myeloid leukocyte trafficking to malignant tumors to identify novel therapeutic targets for innovative immuno-oncological treatment strategies.

Department of Neurosurgery, 
Klinikum Großhadern, LMU 
Munich, Germany

E-Mail: Tao.xu@med.uni-muenchen.de

Project Title: Validate and improve the treatment effects of CAR T cells against brain metastases from lung 
cancer

Lung carcinoma represents the primary contributor to global cancer-related fatalities, 50% of 
patients develop brain metastases throughout disease progression. The median survival time 
of patients with brain metastases accepting current treatment strategies is < 12 months. CAR 
T cells emerged as a powerful treatment for hematological malignancies, however, the 
treatment effect of CAR T cells against solid tumor is limited, especially in brain tumors. To 
uncover the underlying mechanisms leading to its failure, we established a syngeneic 
orthotopic immunocompetent brain metastasis model in mice by combining a chronic cranial 
window with repetitive intracerebral two-photon laser scanning-microscopy. This approach 
enabled the in vivo-characterization of anti-tumor effects of fluorescent CAR T-cells and 
cerebral lung cancer metastasis on a single-cell level over weeks, including the migration,
infiltration and persistence of CAR T cells inside tumor area, and interaction between CAR T 
cells and tumor cells or tumor associated macrophages/microglia. With the expertise in 
neurosurgery, coupled with the experience of mouse model in the field of cellular 
immunotherapy, continues our research in the field of CAR T treatment for brain malignancies, 
furthermore, we are establishing a mouse model to dissect neurotoxic side effects during CAR 
T cell treatment.