Laboratory of Lymphocyte Signaling and Oncoproteome
The work of our laboratory centers around the pathogenetic mechanisms in lymphatic malignancies of T-cell and B-cell lineage. Current progress in these tumors towards improved treatment regimens that target relevant molecular mechanisms of tumor cell survival and growth is hampered by our limited understanding of critical transforming and progression pathways including their chronological sequence and hierarchy of dependence at the stage of overt diagnosed disease. Malignant tumors of the lymphatic system, the lymphomas and their pattern subset of lymphatic leukemias, are derived from particular stages of lymphocyte development and preserve many of the precursor cell’s activation pathways, i.e. those mediated through cytokine or antigen receptors, however, often in a dysregulated fashion.
We are constantly seeking enthusiastic PhD students, MD students and postdocs who would like to get involved in our research.
Currently we are searching for a highly motivated postdoc with experience in T-cell-biology.
Please inquire at: marco.herling@uk-koeln.de
Scientific Focus
Our laboratory focuses on targetable molecular events of malignant lymphocyte transformation and evaluation of such pathway dependence, with particular interest in the pathogenetic mechanisms of chronic lymphoid leukemias. These comprise a heterogeneous group of tumors derived from mature (peripheral) lymphocytes of B-cell or T-cell lineage, but share a common fact, namely their near-exclusive incurability with current therapeutic approaches. B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia of adults in the Western world with distinct molecular and clinical subsets being recognized. T-cell prolymphocytic leukemia (T-PLL) can be considered its aggressive T-cell equivalent. It shows a unique molecular signature of activation of the T-cell leukemia 1 (TCL1) oncogene. The exact position of T-PLL in the T-cell histogenetic spectrum also deserves further investigation. Mycosis fungoides / Sezary syndrome (MF/SS), another group of CD4+ T-helper cell derived tumors, present as erythematous cutaneous lymphomas / leukemias. They show interesting phenomena of immunophenotypic and functional drift.
Our research program is closely connected to the clinical trial efforts of the German CLL Study Group (GCLLSG) with headquarters at Cologne University as a translational platform. This is of particular significance in an era of multiple available target-specific inhibitors, whose mechanistic rationale can be tested in the laboratory and transferred into bedsite application in collaboration with corporate partners.
In previous work (MDACC Department of Hematopathology, Lab D. Jones, MD, PhD), we studied the regulation and function of a protooncogene called TCL1. Its abnormal activation leads to chronic leukemias and it has been implicated as a major transforming force in T-PLL and CLL. However, its molecular function is still poorly understood. We were able to establish a novel mechanism of TCL1 action by demonstrating its regulatory involvement in cellular signaling processes that represent major survival and growth pathways in transformed lympocytes.
Specific Research Program
Conceptionally, our projects comprise the analysis of relevant kinase signaling and the involvement of novel coregulatory molecules as well as the interception in respective mechanisms of regulatory protein interplay in subtypes of chronic lymphoid leukemias.
- temporo-spatial kinetics of TCL1 - protein interactions in B-cell receptor and other micromilieu derived signaling in B-CLL
- mechanisms of TCL1 gene regulation and protein turnover
- differential kinase activity and regulation in clinical and molecular subsets of B-CLL
- stage-dependent changes of proteome patterns / kinome profiles in the oncogenesis of mature T-cell leukemias (T-PLL, MF/SS, T-LGL)
Hinrich Abken: CAR-T cells as TCR signaling tools
Björn Schumacher: Transcription-coupled nucleotide excision repair
Rainer Siebert: Epigenetic aberrancies in T-PLL
Ingo Röder: Systems biology and modeling of T-cell oncogenesis
Richard Moriggl: JAK/STAT in T-cell neoplasms
Satu Mustjoki: Drug response and synergy screens
Monika Brüggemann: TCR profiling in T-cell leukemias
Marc-Henri Stern: ATM and ROS signaling
Dimitrios Mougiakakos: Metabolic rewiring of malignant T-cells
The Team
Till Braun, cand. med.
Annika Dechow, SHK
Jana von Jan, Pharmazeutin
Qu Jiang, M.Sc.
Dennis Jungherz, B.Sc.
Aichatou Kondo Ados, Pharmazeutin
Petra Mayer, Lab Manager
Sebastian Oberbeck, M.Sc.
Moritz Otte, cand. med.
Alexandra Schrader, PhD
Johanna Stachelscheid, M.Sc
Laura Stocker, cand. med.
Lisa Thielecke, cand. med.
Linus Wahnschaffe, cand. med.
Ekaterina Weith, MSc