Research

cRel microscopy

Image: Hyunju Oh-Strauß: Confocal immunofluorescence of c-Rel nuclear presence in Germinal Center B Cells

Overview

Our immune system protects us against invasion by foreign pathogens, such as bacteria, viruses and parasites. However, we pay an evolutionary price for our highly efficient and sophisticated immune defense, namely immunopathology. Immunopathologies include exaggerated responses to harmless substances, also termed allergic responses, misguided responses against our own body, which can lead to autoimmune diseases and the uncontrolled expansion of immune cells, which in turn can cause cancer.

We investigate the molecular and cellular mechanisms underlying such disorders. Immune cells can identify foreign microbial components through a host of cell surface receptors. These receptors then relay signals to the nucleus, where transcription factors activate the expression of genes whose protein products help fight the invaders. Misguidance of such signal transduction events can result in autoimmunity and leukemia or lymphomas, the most prevalent cancers of the immune system.

To study critical mechanisms of immunopathology, we employ

  • Genetic loss and gain of function approaches in the mouse
  • Cellular and biochemical approaches


Within the immune systems, the main focus is on B and T lymphocytes and mast cells. In these cells, we investigate the regulation of genes and proteins whose exaggerated functions or malfunctions directly contribute to immunpathologies.

In the context of NF-kB signal transduction we currently focus on the ubiquitin editing enzyme A20/TNFAIP3 and the transcription factor c-Rel. Another central topic is the regulation of mRNA stability by the RING finger proteins Roquin1/2. In addition, we are investigating the role of T cell receptor-expression and signaling on immune-modulating regulatory T (TR) cells and lipid-recognizing NK-like T (NKT) cells.


Research Projects

Overview

The transcription factor c-Rel, central to innate and adaptive immune responses, is directly implicated in oncogenesis. However, the mechanisms by which c-Rel alterations drive human hematopoietic and solid cancers remain unresolved. To address this issue, we established mice that allow for cell type-specific enhanced c-Rel expression and visualization. We will employ these and complementary loss of function models as well as advanced proteomic approaches to define tumor cell-intrinsic roles of c-Rel signaling in lymphoma and colorectal cancer, as well as mechanisms and consequences of c-Rel activity within the tumor immune environment.

More information: http://www.sfb1335.med.tum.de/en(link is external)

Publications related to the project

Kober-Hasslacher, M., & Schmidt-Supprian, M. (2019). The Unsolved Puzzle of c-Rel in B Cell Lymphoma. Cancers, 11(7), 941. https://doi.org/10.3390/cancers11070941 (link is external)

Kober-Hasslacher M, Oh-Strauß H, Kumar D, Soberón V, Diehl C, Lech M, Engleitner T, Katab E, Fernandez Saiz V, Piontek G, Li H, Menze B, Ziegenhain C, Enard W, Rad R, Böttcher JP, Anders HJ, Rudelius M, Schmidt-Supprian M. (2020). c-Rel gain in B cells drives germinal center reactions and autoantibody production. J Clin Invest. https://doi.org/10.1172/JCI124382 (link is external)