Forschung - Research
AG MK1-L01
- Mitglieder (v.l.n.r.): Claudia Dill, Friedrich Stölzel, Desiree Kunadt, Leo Ruhnke, Heidi Altmann
Die Diagnostik und Therapie der Akuten Myeloischen Leukämie (AML) unterliegt einem ständigen Wissen- und Erkenntniszuwachs. Die AG MK1-L01 beschäftigt sich mit verschiedenen Projekten, die in der präklinisch-experimentellen- und im klinisch-translationalen- Forschung angesiedelt sind.
Unsere wissenschaftlichen Projekte beschäftigen sich mit dem Fokus auf der Detektion und der Charakterisierung neuartiger AML-Marker bzw. genetischer AML-Aberrationen und mit dem Hinblick, diese Marker und Aberrationen auf ihre Generalisierbarkeit, Beeinflussbarkeit und ihre prognostische Bedeutung zu untersuchen. Diese Ansätze werden sowohl für die AML bei der Erstdiagnose als auch für die rezidivierte AML nach einer medikamentösen Therapie oder einer allogenen Stammzelltransplantation verfolgt.
Es existieren verschiedene, vielfältige Kooperationen mit anderen Arbeitsgruppen und Forschergruppen – auf dem Campus des Universitätsklinikums existiert eine enge Kooperation mit dem Stemcell Lab (http://stemcell-lab-mk1dresden.de).
Ein beispielhafter Überblick über aktuelle Themen:
- Etablierung und Charakterisierung genetischer Aberrationen und neuartiger Marker bei der extramedullären AML
- Charakterisierung der prognostischen Relevanz genetischer Polymorphismen und Mutationen in Subgruppen der AML an primären AML Zellen und Keimbahnmaterial
- Bedeutung von TET2 Mutationen bei der AML
- Diagnostik und Charakterisierung HLA-restringierter Rezidivmechanismen nach allogener Stammzelltransplantation
- Charakterisierung des Mutationsmusters bei spezifischen, zytogenetisch definierten Subgruppen der AML
- Etablierung und Charakterisierung neuartiger Marker bei der Akuten Promyelozytenleukämie (APL)
- Charakterisierung und Modulation mesenchymaler Stromazellen (MSC) und Ihrer Matrix im Gesunden und bei myeloischen Neoplasien
Kontakt
Bei Interesse an einer Kooperation, Interesse an einem spezifischen Projekt oder Interesse zur Durchführung eines Projekts, kontaktieren sie uns bitte unter:
Universitätsklinikum Dresden, Medizinische Klinik 1 (MK1)
MK1-L01
Fetscherstr. 74, 01307 Dresden
+49- 0351 458-2699
E-Mail
Bereich Hämostaseologie
In der Hämostaseologie werden grundsätzlich Patienten mit thrombotisch/thrombophilen bzw. hämorrhagischen Gerinnungsstörungen betreut. Diese prinzipiellen Behandlungsschwerpunkte sind am UKD in der klinischen Versorgung, aber auch im Forschungsprofil gut zu unterscheiden und jeweils durch Spezialisten besetzt.
AG „Klinische Thromboseforschung“ (Leitung Prof. Dr. J. Beyer-Westendorf)
- Diagnostik der venösen Thromboembolie
- Prophylaxe und Therapie der Beinvenenthrombose und Lungenembolie
- Antikoagulationstherapie
- Management von Blutungen unter blutverdünnender Therapie
- Registerstudien zu „Alltagsdaten“ in der Antikoagulation und im Blutungsmanagement
Publikationsliste: pubmed
AG „Hämorrhagische Diathesen“ (Leitung: Fr. Dr. K. Trautmann)
- Therapie der Hämpohilie und anderer hämorrhagischer Diathesen
- Registerstudien zu „Alltagsdaten“ in der Hämophilie
Publikationsliste: pubmed
Transplantation Immunology Lab (AG TxI)
Introduction
As part of the Excellence Cluster and in collaboration with the German Bone Marrow Donor Centre (DKMS), our lab focuses on the biology and function of immune effector cells after transplantation in patients with leukemia. In particular, T cells and natural killer (NK) cells are studied in various functional and molecular aspects.
Projects
About T cell research
Acute myeloid leukemia is a heterogenous malignant disease of the hematopoietic system. Therapeutic options for treating AML are still limited, with allogeneic hematopoietic cell transplantation (alloHCT) being the only curative approach for most patients. Treatment with leukemia-specific T-cells might help to avoid the risk of an alloHCT or further improve it’s efficacy.
T cells play an important role in the immune response against leukemia. T cells are able to kill cancer cells after recognition of neo-epitopes presented by major histocompatibility complexes class I molecules (MHC I) on the cell surface. The key molecule on the surface of T cells which defines specificity is the T-cell receptor (TCR).
However, remaining challenges have limited the discovery of leukemia-specific T cells. First, T cells specific for a given leukemia antigen are very rare in the peripheral blood. Second, only a small number of immunogenic leukemia specific epitopes is known. Third, both TCRs and MHCs are polyspecific, allowing binding of several peptides with sequence similarity. Fourth, the affinities of TCRs to peptide MHC complexes might be very low.
A promising approach to detect leukemia-specific T cells is the antigen-directed detection method, which consider exclusively leukemia-specific antigens and the use of the sensitive multimer technology for detection. Our research group works on this approach (see Figure 1)
to (I) identify and isolate novel leukemia-specific T cell clones by multimer technology and flowcytometry,
to (II) to characterize the leukemia specific T cells by multi-color flowcytometry and flowcytometry based degranulation assays and
to (III) sequence the TCR of functional leukemia-specific T cells for the use in T cell-based immunotherapy for leukemia patients after transplantation.
Figure 1. Workflow for the Detection of Neoantigen-specific T cells.
NK-cell research
Natural killer (NK) cells play a pivotal role in the immune response against malignant cells. After HCT for leukemia, donor derived NK cells have the potential to attack residual leukemic cells - thereby contributing to the prevention of relapse. Anti-leukemic activity of NK cells might depend on the gene content of the donor, who is equipped with a donor specific set of NK cell receptor genes. Killer-cell Immunoglobulin-like Receptor (KIR) genes are of special interest for our group.
We would like to investigate whether information on the constitution of donor KIR genes in combination with the patients KIR ligands might be exploited for optimizing HCT-donor selection in order to improve success of the therapy. Therefore we analyze phenotype and function of peripheral blood NK cells or of generated NK-cell clones and correlate results to genetic information on KIR and KIR ligands. The immunophenotype of NK cells is characterized by us using multi-color flowcytometry and CyTOF. Degranulation and cytotoxic potential is evaluated by flowcytometry-based functional assays with primary AML blasts, and genetically and phenotypically characterized cell lines as target cells.
Figure 2. NK cells mediated killing of leukemic cells triggered by missing inhibitory ligands on target cell.
Members
Prof. Dr. med. Johannes Schetelig
johannes.schetelig@uniklinikum-dresden.de
+49- 0351 458-15604
Dr. rer. nat. Falk Heidenreich
falk.heidenreich@uniklinikum-dresden.de
+49- 0351 458-2924
Dr. rer. nat. Elke Rücker-Braun
elke.ruecker-braun@uniklinikum-dresden.de
+49- 0351 458-2924
Dr. rer. nat. Dana Vu Van
dana.vuvan@uniklinikum-dresden.de
+49- 0351 458-2924
Heike Uhlemann
heike.uhlemann@uniklinikum-dresden.de
Nicole Heymann
nicole.heymann@uniklinikum-dresden.de
AG AI in Cancer
Als interdisziplinäre Arbeitsgruppe an der Schnittstelle zwischen Medizin und Informatik ist es unser Ziel, die Diagnostik und Therapie in der Hämatologie und Onkologie mithilfe intelligenter Technologien entscheidend zu verbessern. Wir benutzten dazu 'Big Data' aus verschiedenen Bereichen präklinischer und klinischer Forschung. Damit entwickeln wir Systeme zur Computer-gestützten Entscheidungsfindung und treiben die Personalisierung in Diagnostik und Therapie für den individuellen Patienten weiter voran.
siehe auch: AI in Cancer
Kontakt
AG Myelodysplastische Syndrome
Welcome to the website of the Dresden MDS Working Group!
Our aim is to provide current and novel therapeutic strategies for patients with Myelodysplastic Syndromes (MDS) and to explore the pathobiology of this disease in a translational way.
Our main research interests include:
- Dissecting inflammatory pathways in MDS with a particular emphasis on S100A8/9
- Revealing specific metabolic signatures in various cellular and humoral compartments of MDS patients
- Investigating the role of the microbiome in MDS pathobiology
- Novel diagnostic tools
We are honored to possess close collaborations with the Dresden Stem Cell Lab, the Institute for Clinical Chemistry and Laboratory Medicine, the working group “AI in cancer”, the working group “Oncomechanics”, the German MDS Study Group and EMBL Heidelberg.
We are always open to new ideas and collaborations - feel free to contact us.
Our department is certified as an “MDS Center of Excellence” by The Myelodysplastic Syndrome Foundation, Inc..
contact
- Dr. med. K. Sockel Katja Sockel
- Dr. med. E. Balaian Ekaterina Balaian
AG Improvements in clinical cellular immunotherapies
Current research
Our lab focuses on anti-neoplastic immune effector cell (IEC) therapies including CAR T cells and macrophages. This encompasses clinical and laboratory elements related to IEC application. Building on our findings on the disturbance of the bone marrow microenvironment with emphasis on mesenchymal stromal cells (MSCs) in steroid-refractory graft versus host disease (GvHD), we are particularly interested in changes within the bone marrow stroma which might contribute to IEC-associated protracted hematotoxicity.
Background
Cellular therapies have evolved within the context of hematopoietic cell transplantation (HSCT). In parallel, adoptive immunotherapies outside of HSCT have also proven the capability of cell based immunotherapies to kill tumors. This particularly gained momentum with advances in genetic engineering. Chimeric antigen receptor modified T lymphocytes (CAR T) targeting CD19 were the first living, genetically modified drugs that received approval in 2017. However, besides effectiveness, tolerability will be the key to clinical success. Our group investigates how to manage pleiotropic systemic inflammatory effects of immunotherapies and thus to improve cancer care.
Research aims
- Deciphering immune effector cell associated hematotoxicity
- Understanding the clinical relevance of macrophages as new cell therapeutic agents for cancer treatment in cooperation with Sieweke Lab
More information and lab members
Contact
Stem Cell Lab 2 (MK1-L11)
Background
Located within specific anatomical zones of the skeleton, the bone marrow (BM) is a specialized microenvironment or “niche” that lodges cells of hematopoietic and mesenchymal origins in various hierarchical committed states. The main role of the BM niche is the tight control of cell-fate decisions of the hematopoietic stem cells (HSCs) and their progeny to sustain the daily supply in functional blood and immune cells throughout life. These environmental cues are produced by a variety of stromal cells that constitute the BM niche which mainly include neurons, endothelial cells and mesenchymal stromal cells (MSCs). The latter are considered a versatile stem cell population due to their capacity to differentiate into bone (osteoblasts), cartilage (chondrocytes) and fat cells (adipocytes), thus playing a central role in HSCs maintenance, BM niche composition and life-long turnover and bone growth.
In health, the bone marrow niche maintains a harmonious interplay between different cellular entities, including HSCs, MSCs, endothelial cells, immune cells, and osteoblasts, as well as an intricate network of signaling molecules. This spatial organization is not static but dynamically influenced by temporal factors, such as circadian rhythms, aging, and responses to physiological stresses. The collective effect of this spatial-temporal crosstalk determines the fate decisions of HSCs, balancing their self-renewal, quiescence, and differentiation to sustain a functional hematopoietic system.
The balanced BM homeostasis can be disrupted, giving rise to a spectrum of hematologic pathologies. Dysregulation of the spatial-temporal crosstalk has been implicated in BM failure syndromes, hematopoietic malignancies, and other disorders affecting blood cell production but also different treatment strategies such as chemotherapy and stem cell transplantation.
Research
The group of Manja Wobus has long-term translational research experience in the field of Myelodysplastic Neoplasms (MDS) and Acute Myeloid Leukemia (AML). The major research focus of our group is on the characterization of the interaction of HSCs and leukemic clones within the bone marrow microenvironment and the consecutive bidirectional sequelae. Along these lines, highly innovative 2D and 3D co-culture models have been developed to delineate the impact of the stromal environment on the leukemogenesis and disease persistence, interrogating the role of MSC-derived extracellular matrix (ECM) and vesicles (EVs) as well as cell-cell interactions in patients with MDS and AML.
PhD projects
- Metabolic reprogramming of the hematopoetic microenvironment in acute myeloid leukemia (Anastasia Sidorenkova)
- 3D bone marrow niche mimics for drug screening and the development of new therapeutic strategies for AML (Hannah Botterer)
Further projects
- The role of extracellular matrix ECM for malignant transformation
- Monocyte-MSC crosstalk in the myelodysplastic BM microenvironemt
- Impact of stromal-leukemic cell interactions for therapy response
Members
- Prof. Dr. rer. nat. Manja Wobus, group leader
- Anna-Lena Baumann, M.Sc., research associate
- Dipl. Biochem. Kristin Möbus, technician, academic coordination
- Katrin Müller, technician
- Robert Kuhnert, technician
- Anastasia Sidorenkova, PhD student
- Hannah Botterer, PhD student
