Dr. Marco Herling

Principal Investigator, CECAD Cologne


Dr. Marco Herling
Principal Investigator, CECAD Cologne
 +49 221 478 5465

Klinik I für Innere Medizin
Uniklinik Köln
Kerpener Str. 62
50937 Köln

Dr. Marco Herling and his team explore in detail the abnormal signal transfer within T and B lymphocytes, which causes them to escape controled responses to impulses by the microenvironment, which in turn causes them to degenerate into leukemic cells. The laboratory focuses on the adapter protein TCL1. It amplifies signals from the antigen receptor or renders DNA repair inefficient and as such functions as an unconventional oncogene.

Our research: Aberrant intermolecular signaling inside T and B lymphocytes causes these cells to evade a regulated response to growth and apoptotic impulses and to eventually proliferate autonomously. The TCL1 protein plays a central role therein, by acting as an adapter molecule. By amplifying signals from the environment it acts as a sensitizer, especially towards antigen receptor input. It also seems to have a negative influence on the activity of the DNA repair enzyme ATM. The group headed by Dr. Marco Herling is interested in the processes that trigger TCL1 overexpression in the lymphocytic cells. Furthermore, the lab investigates the effector proteins TCL1 binds to and uses for its oncogenic effect alongside possible differences in these mechanisms between T vs B lymphocytes. The overall goal is to understand how such rewired signaling pathways are amenable to interventional approaches.

Our successes: Dr. Marco Herling and his group have successfully established TCL1 as a diagnostic tool and prognostic marker. Moreover, some mechanisms of its dysregulation could be described at the cellular and molecular level. For example, stimuli from stromal cells and abnormally expressed TCL1-repressive micro-RNAs can maintain high cellular concentrations of TCL1. The team also discovered that TCL1 interacts with the kinases AKT and ATM as its major executioners, which in turn can represent targetable Achilles’ heels of leukemic cells.

Our goals: The scientists aim to further expand their understanding of the leukemogenic mechanisms of TCL1 by developing a detailed concept of the upstream modes of TCL1 dysregulation and the downstream effects in lymphocytes and their derived tumors. This has to be extended to the role of TCL1 in embryonic stem cells and tumor-initiating cells of solid neoplasms.

Our methods/techniques: The team applies methods that characterize protein-protein interactions, including mass spectrometry. The cell biologic and biochemical effects of TCL1-modulated protein complexes are explored in genetically engineered model organisms such as mice and cell lines (knockdown, mutagenesis, etc.).


Figure 1: Surface domains of the TCL1 adapter protein; hydrophobic areas in yellow.

Figure 2: TCL1 can physically engage a multitude of targets and elicit tumorigenic activations of several signaling cascades with a lymphocyte-permissive net effect.

EXTERNAL Cooperations
  • Prof. Dr. H. Abken, ZMMK, Cologne, DE
  • Dr. S. Newrzela, Goethe University Frankfurt, DE
  • Prof. Dr. A. Rosenwald, University of Würzburg, DE
  • Prof. Dr. M. H. Stern, Institute Curie Paris, FR
  • Prof. Dr. M. Trepel, Klinikum Augsburg, DE