Clinician Scientists in Oncology

Clinician Scientist Program: Clinician Scientist Program in Evolutionary Medicine (CSEM)

Modeling disease dynamics in leukemias in the context of therapy resistance

In addition to my clinical work, it was very difficult to pursue my research interests and academic goals. That is why I joined the “Clinician Scientist Program in Evolutionary Medicine” (CSEM) in 2019. By providing dedicated time for research, a structured continuing education curriculum, and the soft skills training necessary for an academic career, the CSEM offers me a clear path to habilitation and certification as a specialist in hematology and oncology. Additionally, the CSEM helps me better balance family and career.

My research focuses on B-cell acute lymphoblastic leukemia (ALL), an aggressive form of blood cancer, and its interaction with the immune system. Even with the use of immunotherapeutic approaches, a significant proportion of patients relapse or do not respond to treatment. In contrast to chemotherapy, which primarily kills rapidly proliferating cells, immunotherapy (T-cell-activating therapeutic approaches) targets all cells that express the target antigen (e.g., CD19). Accordingly, the course of minimal residual disease differs between these two therapeutic approaches. As part of the CSEM in cooperation with the Max Planck Institute for Evolutionary Biology (under the supervision of Prof. Monika Brüggemann, Hematology Laboratory Kiel, Medicine II, UKSH Kiel, and Prof. Arne Traulsen, Max Planck Institute for Evolutionary Biology, Plön), we are modeling the course of minimal residual disease under chemotherapy versus immunotherapy approaches in ALL to identify the best possible treatment sequences with optimal outcomes. The immunophenotypic and genetic characterization of T cells and leukemic cells using flow cytometry, high-throughput sequencing, and single-cell RNA sequencing enables us to better understand the mechanisms of action and resistance of these novel therapeutic approaches, to better identify patient cohorts that may benefit from treatment, and to optimize outcomes.

Clinician Scientist Program: Clinician Scientist Program in Evolutionary Medicine (CSEM)

Evolution of oncogenic signaling in acute lymphoblastic leukemia

Acute lymphoblastic leukemias (ALL) arise from malignant transformations in early lymphoid progenitor cells. Despite significant therapeutic advances, some molecular subgroups continue to have a poor prognosis. As part of a project funded by the German Research Foundation (DFG) within the Clinician Scientist Program in Evolutionary Medicine, I am investigating how oncogenic signaling pathways change during normal cell development and contribute to the development of leukemia. To this end, we compare healthy lymphoid progenitor cells with the corresponding ALL subtypes and analyze the underlying molecular patterns, including changes in gene regulation and epigenetics. A particular focus is on the precise characterization of B-ALL with CEBP gene fusions, as well as on the introduction of modern long-read sequencing, which allows genetic and epigenetic changes to be detected more quickly and comprehensively. The goal is to better understand the cellular developmental origins of various ALL subgroups, define them more precisely for diagnostic purposes, and derive both new biomarkers and potential therapeutic targets from this understanding, with the aim of enabling faster, more precise diagnostics and more targeted therapy for patients in the future.

Clinician Scientist Program: Clinician Scientist Program in Evolutionary Medicine (CSEM)

Structure, Mutation, and Therapy: Innovative Research on the Development and Treatment of AML

Since May 2021, I have been a member of the Clinician Scientist Program in Evolutionary Medicine (CSEM), funded by the German Research Foundation (DFG). This program allows me to combine my clinical training as a specialist in internal medicine, hematology, and oncology at the Department of Internal Medicine II on the Kiel campus with my research.

My research focuses on acute myeloid leukemia (AML), a disease of the bone marrow that primarily affects older populations (mean age at diagnosis 65–75 years). Against the backdrop of an increasingly aging population, AML continues to gain clinical relevance despite its rarity. Over the past 10–20 years, genetic analyses have led to significant advances in our understanding of AML pathogenesis, which has already resulted in improved treatment options. In addition to classical genetic mutations, epigenetic changes and the three-dimensional structure of the genome are increasingly coming into focus, as these control gene expression and thus the course of the disease.

My CSEM project investigates these 3D DNA structural changes in AML. The goal is to understand the impact of known mutations on DNA architecture, classify their role in the onset, maintenance, and progression of the disease, and use these findings to identify mechanisms of treatment resistance. The findings are intended to enable new therapeutic approaches in the context of translational research and to be promptly translated into improved treatment strategies.

The scientific work is complemented by a series of publications, including national and international analyses on the epidemiology and treatment of AML, real-world data on GvHD prophylaxis following allogeneic stem cell transplantation, as well as studies on the role of mutations and epigenetic changes in leukemia development. Additional work focuses on therapy-induced complications and prognostic factors in AML. By combining clinical expertise, translational research, and epidemiological analyses, my project contributes to a better understanding of the development and treatment of AML and, in the long term, to improving care for patients with this complex disease.

Clinician Scientist Program: Clinician Scientist Program in Evolutionary Medicine (CSEM)

Dysregulation of Antimicrobial Peptides and Microbiome Analysis in Patients with Cutaneous T-Cell Lymphomas

In a previous analysis, we were able to demonstrate that an antimicrobial peptide is dysregulated in patients with cutaneous T-cell lymphomas. Since this suggests changes in the microbiome, we now intend to conduct further analyses for more precise detection.
Cutaneous T-cell lymphomas are a group of non-Hodgkin lymphomas characterized by clonal expansion of CD4+ T cells in the skin. The etiopathogenesis remains unclear, and a cure is currently not possible. However, stage-adapted therapy can successfully control the disease, particularly in the early stages.

It is conceivable that changes in the microbiome of these patients correlate with the course of the disease. The majority of patients exhibit a slowly progressive course, but there are some who rapidly develop skin tumors and ultimately die from the disease or from related complications, such as sepsis.

The aim of this study is to identify potential factors influencing the development and/or maintenance of cutaneous T-cell lymphomas and, if possible, to generate new therapeutic approaches.

Clinician Scientist Program: Clinician Scientist Program in Evolutionary Medicine (CSEM)

Intratumoral Heterogeneity and Neuroendocrine Neoplasms

In the Konukiewitz Laboratory, we investigate the molecular mechanisms, diagnostic markers, and prognostic implications of neuroendocrine differentiation in neoplasms of various sites (gastrointestinal tract, pancreas, lung, ovary, etc.) and are working on a morphomolecular characterization of these tumors and their microenvironment.

Another focus is the analysis of intratumoral genetic heterogeneity in colorectal carcinomas through comparative whole-exome sequencing of the individual histological subtypes of morphologically heterogeneous colorectal adenocarcinomas and neuroendocrine carcinomas to guide the adaptation of molecularly targeted therapeutic approaches.

In addition, I investigate diagnostic targets and the interaction between fibroblasts and the immune system in the microenvironment of endometriosis and ovarian carcinoma.

Clinician Scientist Program: Clinician Scientist Program in Evolutionary Medicine (CSEM)

Evolutionary Dynamics of Clonal Hematopoiesis in Cancer and Inflammation

Since 2019, I have been part of the Clinician Scientist Program in Evolutionary Medicine (CSEM), funded by the German Research Foundation (DFG). The program allows me to closely integrate my clinical work in internal medicine, with a focus on hematology and oncology at the UKSH, Kiel Campus, with scientific research and to pursue my academic goals in a structured manner.
In my research project, I focus on what is known as clonal hematopoiesis. This refers to acquired genetic changes in blood stem cells that occur primarily in older adults and can persist for long periods without any detectable blood or cancer-related disease. These changes are considered potential precursors to hematological diseases and are also associated with chronic inflammatory processes as well as cardiovascular and metabolic diseases. A central focus of my work is on how these genetically modified cell clones develop over time and what impact they have on the onset and course of treatment for hematological diseases. The goal is to identify risk factors at an early stage and, in the long term, to contribute to more precise, individually tailored diagnostics and therapy. The project is being conducted within the framework of the CSEM in cooperation with and under the supervision of PD Dr. Martin Neumann (Department of Internal Medicine II, UKSH Kiel) and Prof. Dr. Arne Traulsen (Max Planck Institute for Evolutionary Biology, Plön).

Clinician Scientist Program: Clinician Scientist Program in Evolutionary Medicine (CSEM)

Analysis of the Evolution of Molecular and Immunological Resistance Mechanisms in Gastrointestinal Tumors

Since May 1, 2020, I have been working as a clinician-scientist and a resident in internal medicine, hematology, and oncology at the Department of Hematology and Oncology on the Kiel Campus. In my project, “Analysis of the Evolution of Molecular and Immunological Resistance Mechanisms in Gastrointestinal Tumors,” I am investigating the development of resistance mechanisms against established and experimental drug therapies for gastrointestinal carcinomas. Particular emphasis is placed on the role of the immune system and the establishment of patient-relevant in vitro models, known as organoids, to make better predictions about potential treatment response. The long-term goal is to contribute to the development of more tailored and personalized treatment strategies.

Clinician Scientist Program: Clinician Scientist Program in Evolutionary Medicine (CSEM)

Understanding and Overcoming Apoptosis Resistance in Breast Cancer: Leveraging Synergistic Effects of Cytostasis (Palbociclib) and Cell Death (TRAIL)

Breast cancer is the leading cause of cancer death among women worldwide. Since 2016, a new class of drugs known as CDK4/6 inhibitors has been used very successfully in the treatment of metastatic hormone receptor-positive/HER2-negative breast cancer. CDK inhibitors, such as palbociclib, inhibit cyclin-dependent kinases (CDKs), which are key enzymes in the cell cycle and thus in cell proliferation. Inhibition of CDK4 and CDK6 leads to cell cycle arrest, and the tumor cells’ greatly increased proliferation is inhibited. This is therefore a cytostatic drug that halts disease progression but cannot primarily cause the death of tumor cells and thus bring about a cure. The death ligand TRAIL (TNF-related apoptosis-inducing ligand) represents a promising candidate for combination therapy with CDK4/6 inhibitors. As we have demonstrated in extensive preliminary work, prior cell cycle arrest via CDK4/6 inhibition leads to increased sensitivity to TRAIL and thus to enhanced cell death. Even tumor cells previously considered resistant to apoptosis can thus be resensitized to TRAIL-induced cell death. Our preliminary work using a panel of human breast cancer cell lines demonstrates a synergistic effect between cytostasis (palbociclib) and cell death (TRAIL), underscoring the significant therapeutic potential of this strategy for cancer treatment.

The aim of the project is to further investigate the mechanisms of action and the conditions under which a combination therapy of palbociclib and TRAIL leads to the overcoming of breast cancer cell resistance in 2D and 3D cell culture models.

Clinician Scientist Program: Clinical Scientist Program (interdisciplinary) at the Faculty of Medicine, Kiel University

Establishing Early Detection Methods and Overcoming Resistance Mechanisms in the Treatment of Ovarian Cancer

Ovarian cancer has the highest mortality rate among gynecological cancers. There are two main reasons for this: the lack of reliable biomarkers and the risk of developing resistance to chemotherapy. Our research group is therefore attempting to address these challenges by searching for new biomarkers and investigating potential mechanisms of chemoresistance. We focus particularly on A-desintegrin and metalloproteinase 17 (ADAM17) and its downstream signaling pathways. ADAM17 is activated by chemotherapy, which leads to the activation of receptor tyrosine kinases (RTKs) and the initiation of survival pathways. Our goal is therefore to identify novel combination therapies that counteract this signaling pathway and resensitize the cells to therapeutic treatment. In addition, we collect, process, and analyze patient samples, including cells, serum, and ascites, to investigate new biomarkers that provide insights into prognosis and response to therapy.

Clinician Scientist Program: Clinical Scientist Program (interdisciplinary) at the Faculty of Medicine, Kiel University

Extramedullary AML: Integrated Pathobiological Characterization and Translational Therapy Development

In addition to my clinical work at the Department of Hematology and Oncology, particularly in the Division of Stem Cell Transplantation and Cellular Immunotherapy, the Clinician Scientist Program offers me the opportunity to conduct scientific research on the biology of extramedullary relapses of acute myeloid leukemia (AML).

Today, a large proportion of patients with AML can be offered curative therapy at the time of diagnosis. Allogeneic hematopoietic stem cell transplantation plays the most important role as the most effective treatment option in first remission or in second remission (i.e., after a relapse). Recurrence of AML is the most common cause of death following both conventional therapy and allogeneic hematopoietic stem cell transplantation. Recurrence of AML frequently occurs in the bone marrow and/or peripheral blood. However, both after conventional therapy and after allogeneic hematopoietic stem cell transplantation, extramedullary AML recurrence can also occur. This means that AML leukemia cells appear in extramedullary manifestations. This extramedullary AML then presents as localized, solid tumor masses consisting of leukemia cells that displace and destroy surrounding tissue and exhibit expansive growth.

My scientific interest lies in deepening our understanding of extramedullary AML and developing innovative treatment approaches.

Clinician Scientist Program: Clinical Scientist Program (interdisciplinary) at the Faculty of Medicine, Kiel University

Targeting oncogenic proteins: Advancing PROTAC therapy for acute lymphoblastic leukaemia (ALL)

In July 2023, I began my first position as a resident in the Department of Hematology and Oncology at the University Medical Center Kiel (UKSH). In order to pursue ambitious research projects alongside my clinical work, I applied to become a clinician-scientist. I am delighted to have been part of the program at the Medical Faculty of Kiel University (CAU) since April 2024.

As part of my research project in the “CATCH ALL” Clinical Research Group, we aim to investigate protein degradation as a new approach to treating acute lymphoblastic leukemia, in collaboration with the Institute of Biochemistry at CAU Kiel (led by Prof. Elmar Wolff). Targeted protein degradation represents an innovative principle for the development of new therapeutic agents. The goal of this method is to remove disease-driving or causative proteins from the affected cells by directing them to the cell’s own protein degradation apparatus (the so-called proteasome). This principle can be utilized therapeutically, for example, via “Proteolysis Targeting Chimeras” (so-called PROTAC degraders).
The key advantage of protein degradation via PROTACs, compared to binding-based inhibition—e.g., using small inhibitory molecules or therapeutic antibodies—is that it allows for the targeting and elimination of proteins that were previously considered untreatable (“undruggable”).

In addition, PROTACs have the potential to cause fewer side effects than existing inhibitors. In the first phase of the research project, potential candidate proteins for protein degradation will be identified based on expression data and genetic screens, among other methods. Since the development of PROTACs is complex and time-consuming, we intend to first validate the identified candidates in cellular and murine models. To this end, we plan to use Auxin-Inducible Degron (AID) technology, as it represents a simple method of protein degradation that, mediated by the addition of the hormone auxin—which occurs exclusively in plants—causes rapid and selective degradation of target proteins. This enables mechanistic investigations of targeted protein degradation, which allow conclusions to be drawn about the effects of corresponding PROTACs. The insights gained are intended to contribute to the development of PROTACs for the treatment of ALL. The goal is to propose new targeted therapeutic approaches for subgroups that have not yet been treated or have been treated inadequately, and to develop treatment options with fewer side effects.

Clinician Scientist Program: Clinical Scientist Program (interdisciplinary) at the Faculty of Medicine, Kiel University

Detection of Genomic Imbalances and Their Application in the Diagnosis of Ovarian Cancer

In Germany, ovarian cancer is the second leading cause of death from gynecological cancers. Approximately one in every 72 women will develop the disease during her lifetime. At the time of initial diagnosis, patients are often already in advanced stages of the disease, which leads to a poor prognosis despite advances in drug and surgical treatments. Diagnosing ovarian cancer in its early stages poses a particular challenge, as patients exhibit few early symptoms and currently known blood-based tumor markers are not reliably suitable for establishing a diagnosis. The goal of our research group is therefore to close this diagnostic gap and to explore possibilities for the early detection of ovarian cancer.

Tumor cells harbor mutations in their genome that, among other things, cause cellular dysfunction—such as through oncogenes—resistance to the body’s own repair mechanisms, and malignant transformation. These changes are caused by a variety of events, such as chromothripsis or chromoanasynthesis, which can lead to the rearrangement, duplication, or deletion of chromosomal segments. The resulting changes are referred to as “genomic chaos” and manifest as structural and numerical alterations in the genome of tumor cells. These tumor-specific genomic imbalances can be detected in peripheral blood. The characterization of these alterations in ovarian cancer, as well as the development of new methods for their detection, constitute the overarching goal of our research group. This is intended to improve the possibilities for early detection and treatment monitoring of ovarian cancer.

Clinician Scientist Program: Clinical Scientist Program (interdisciplinary) at the Faculty of Medicine, Kiel University

Preclinical Evaluation of the Efficacy of the HER2 Antibody Conjugate Trastuzumab Deruxtecan in Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and also occurs in adults. Current treatment protocols are based on intensive polychemotherapy, which is associated with significant side effects. The identification of new antibody-based immunotherapies is urgently needed for the targeted and effective treatment of ALL, particularly T-ALL, for which few immunotherapy options are available.

Trastuzumab, an antibody targeting the human epidermal growth factor receptor 2 (HER2), is currently used successfully in the treatment of HER2-positive breast cancer. The antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) demonstrates significantly enhanced efficacy and has even shown a doubling of event-free survival in patients previously classified as HER2-negative.

In approximately 30% of B-ALL cases, some HER2 surface expression can be detected, and our own preliminary data show that trastuzumab is internalized by ALL cells. We therefore hypothesize that ALL patients may also benefit from T-DXd therapy. As part of this research project, we will therefore i) validate the expression of Her2 in primary B-ALL and T-ALL cells and ii) test the efficacy of T-DXd on ALL cells in vitro (in collaboration with AG Peipp, Department of Internal Medicine II). Subsequently, iii) the efficacy of T-DXd will be investigated in vivo in patient-derived xenograft (PDX) models. Additionally, iv) a drug screening platform will be established for the prospective pre-testing of T-DXd and other ADCs in primary ALL cells (in collaboration with AG Baldus, P1 Catch-ALL, Department of Internal Medicine II).

Clinician Scientist Program: Clinical Scientist Program (interdisciplinary) at the Faculty of Medicine, Kiel University

Resistance and Response Factors in CAR-T Cell Therapy for B-Cell Lymphomas

CAR-T cell therapy has revolutionized the treatment of B-cell lymphomas and represents an enormous therapeutic advance in the management of this disease. Nevertheless, the majority of treated patients experience primary treatment failure or relapse. The underlying resistance mechanisms are not yet fully understood.

The goal of this project is to contribute to a better understanding of these mechanisms in order to develop targeted strategies to overcome them. To this end, we have focused on the investigation of circulating tumor DNA, the significance of extracellular vesicles in CAR-T cell therapy, and the establishment of cytotoxicity assays using ex vivo-derived CAR-T cells. Together with various basic science and clinical partners at the UKSH and beyond, we aim to contribute to the further development of effective and safe CAR-T cell therapy.

Clinician Scientist Program: UCCSH Clinician Scientist Program

Real-World Data for Precision Oncology

My research focuses on the measurability of clinical phenomena in everyday oncology care. Many relevant factors—treatment toxicity, symptom burden, functional status—are either not recorded at all, recorded inconsistently, or recorded only as secondary measures in clinical practice. Before reliable models and analyses are possible, a database is needed that does justice to these phenomena. I view this step—the systematic collection and quality assurance of clinical measurement data—as an independent scientific contribution.

To this end, I draw on both traditional secondary data sources and primary sources directly, including: chemotherapy data, physician reports, and pathology reports. The integration of these heterogeneous sources—relational databases, hierarchical data models, and medical free-text data from which structured data is extracted using locally operated language models—forms the foundation of an oncology care database at UCCSH, which is under continuous development and enables automated cohort formation as well as retrospective biomarker studies. Current application examples include analyses of the predictive power of CT-derived body composition, serum tryptophan, and spatial multi-omics signatures for clinical and patient-reported outcomes such as fatigue. The requirement for measurement quality can be particularly consistently met in the case of patient-reported outcomes. As the initiator of several healthcare IT projects, particularly a clinical evaluation study on digital PROM data collection, I am driving the implementation of structured measurement tools directly into everyday clinical practice. This approach is being directly applied in the BMFTR-funded PANTHER project, with the goal of developing models to predict individual treatment toxicity.

The only people who can properly assess the limitations and potential of clinical processes and the data generated in everyday healthcare practice are those who understand how these processes work—and who can use appropriate data processing and modeling to derive reliable research findings from them.

Clinician Scientist Program: UCCSH Clinician Scientist Program

The Role of the GFI1-36N Single-Nucleotide Polymorphism in DNA Repair as a Biomarker and Therapeutic Target for Malignant Neoplasms

This project investigates the role of the GFI1-36N single-nucleotide polymorphism in DNA repair and its significance in the development of malignant diseases, particularly leukemias. GFI1 is an important regulator of cellular processes and plays a central role in maintaining genomic stability through efficient DNA repair. In the presence of the GFI1-36N polymorphism, DNA repair is impaired, allowing DNA damage to accumulate more readily. This genetic damage increases the risk of developing leukemias. At the same time, the repair deficiency caused by the genetic variant could be exploited therapeutically by specifically targeting signaling pathways or dependencies of the affected cells. The aim of the project is therefore to identify specific therapeutic targets resulting from the altered DNA repair in order to develop new, personalized treatment strategies.

Clinician Scientist Program: UCCSH Clinician Scientist Program

Inhibition of the Non-Canonical NF-κB Signaling Pathway as a Therapeutic Strategy in Cholangiocarcinoma

Cholangiocarcinoma is an aggressive malignant tumor of the liver that originates from the epithelial cells of the bile ducts and is associated with a poor prognosis. Curative treatment options remain limited, and there is an urgent need for innovative therapeutic approaches.

Our own preliminary work has shown that the non-canonical NF-κB signaling pathway plays an important role in the development and progression of cholangiocarcinoma. Under the mentorship of Prof. Bruno Köhler (Department of Hematology and Oncology, UKSH Lübeck), the Clinician Scientist Program will investigate how therapeutic strategies for manipulating this signaling pathway can be applied to cholangiocarcinoma. To this end, we will investigate selective inhibitors of the signaling pathway—which have so far been used primarily in vitro—in mouse models as well as in patient-relevant systems such as patient-derived organoids and organotypic slice cultures, with the long-term goal of developing new and more effective therapeutic approaches for patients with cholangiocarcinoma.

Clinician Scientist Program: Clinician Scientist Program of the CATCH ALL Clinical Research Group

Lymphoma vs. Leukemia

As part of the Clinical Research Unit (CRU) “CATCH ALL,” my focus is on precursor B-cell lymphomas (B-lymphoblastic lymphomas, B-LBL). In contrast to leukemic diseases of precursor B cells (B-ALL), B-LBL are rare and typically present clinically without, or with only minimal, involvement of the blood and bone marrow. Because the immunophenotype of B-LBL and B-ALL does not differ, both diseases are considered a single entity despite differences in clinical presentation.

We aim to use B-LBL as a model to study immune control and disease dissemination, in order to understand why the disease manifests in tissues outside the bone marrow. Furthermore, compared to other precursor cell neoplasms, B-LBL are associated with a relatively favorable prognosis. Therefore, B-LBL can also serve as a clinical model for low-risk precursor B-cell neoplasms. Because B-LBL are not leukemic, only tissue biopsies are available for research. We use these biopsies, which have been collected over many years in the Hematopathology section, for molecular characterization and compare the findings with B-ALL.

As a future pathologist, I aim to integrate the skills I acquire during my specialist training into my research.  Therefore, histology is a major focus of my work. However, unlike in routine clinical practice, I use multiplex fluorescence staining techniques that are analyzed using digital image analysis. This approach allows me to characterize the non-neoplastic accompanying infiltrate (microenvironment) using complex phenotypes and quantitative parameters. I investigate differences in the microenvironment between B-LBL and B-ALL, as well as other lymphoid neoplasms, to understand whether interactions between B-LBL lymphoma cells and the immune system contribute to the unusual clinical presentation and favorable prognosis of the disease.

Clinician Scientist Program: Clinician Scientist Program of the CATCH ALL Clinical Research Group

Molecularly-guided experimental treatments for patients with relapsed/refractory malignant lymphatic diseases – Project Z-Platform

Treatment for patients with a first diagnosis of acute lymphoblastic leukemia (ALL) is carried out in accordance with treatment protocols established by large study groups (GMALL, ALL-BFM) for both children and adolescents as well as adults. This standardized approach has a high success rate with good chances of cure. In contrast, a different picture emerges for relapsed and refractory (r/r) ALL, particularly when multiple relapses occur: The frequent lack of standardized treatment concepts necessitates individualized treatment modifications, yet a solid evidence base for treatment decisions is often lacking and/or novel, innovative approaches do not exist.

The Z-Project is one of nine subprojects of the KFO CATCH ALL initiative and aims to establish the CATCH ALL Board as a molecular tumor board. It is intended to bring together preclinical, clinical, and experimental expertise, facilitate interdisciplinary discussions, and thereby create a center of excellence for children, adolescents, and adults with r/r ALL.

Clear and well-organized documentation of both clinical and molecular characteristics, as well as follow-up information, in a database helps structure growing volumes of data and makes them accessible for future treatment recommendations.
The Z Project is being carried out in close cooperation with all other subprojects of the KFO CATCH ALL initiative. This close networking enables the translation of preclinical results into clinical practice, but also provides new input for preclinical research through the provision of well-processed patient material (reverse translation).

In addition, through the collaboration of ALL experts from the fields of pediatric and adult oncology, the CATCH ALL Board represents an important step toward implementing a unified care structure for adolescents and young adults (AYA).

Clinician Scientist Program: Clinician Scientist Program of the CATCH ALL Clinical Research Group

Dissection of the human bone marrow niche under transformation by acute leukemia and treatment

As a clinician-scientist on the “CATCH-ALL” project, funded by the German Research Foundation (DFG), my research focuses on investigating the tumor microenvironment in acute leukemias.

Bone marrow arises from the complex interaction of various cell types that form highly specialized niches. In healthy individuals, hematopoietic cells work in conjunction with niche cells to form and maintain the hematopoietic system. In acute leukemias, however, malignant blasts proliferate uncontrollably in the bone marrow, thereby reshaping it to their advantage. As a result, it increasingly loses its original function. Using modern technologies such as highly multiplexed immunofluorescence staining, which preserves the spatial context of the tissue, we aim to characterize changes in human bone marrow architecture and cellular interaction networks during disease and therapy. In this way, we aim to gain a better understanding of the interplay between acute leukemia and its microenvironment—with the long-term goal of making this knowledge therapeutically applicable in the future.

Clinician Scientist Program: Clinician Scientist Program of the CATCH ALL Clinical Research Group

Functional Modules of Oncogenic Signal Transduction in B-Precursor Cells

B-cell acute lymphoblastic leukemia (B-ALL) is a malignant disease of immune precursor cells in the bone marrow. In my clinician-scientist project, I am collaborating with colleagues from the Clinical Research Group kfo5010 “CATCH-ALL” to investigate the role of developmental checkpoints in healthy B-precursor cells in the context of B-ALL. My focus is on the mitogenic niche factor interleukin 7, as well as the pro- and pre-B-cell receptors, which are central regulators of healthy B-cell lymphopoiesis.

We use retroviral overexpression constructs as well as inducible CRISPR-Cas9 knockout constructs to activate and deactivate individual oncogenic signaling cassettes in murine stem and progenitor cells. The functional characterization of these models thus provides insight into the transformative properties of the signaling pathways under investigation. In particular, this approach allows us to describe co-dependencies between the stage of differentiation, primary disease drivers, and secondary alterations.

My project is part of Prof. Claudia Baldus’s Functional Genomics of Acute Leukemias research group. This creates strong synergies with the group’s translational and clinical expertise.

The results of the project will be used to model clinical disease subtypes and will help advance our mechanistic understanding of B-ALL.