Expression of the multi-functional protein TIMP-1, which can act as a protease-inhibitor as well as a cytokine, positively correlates with progression of virtually all immune-associated diseases, including inflammation and cancer. At Krüger Lab they have discovered that TIMP-1 expression determines sex-disparities in liver metastasis and survival in pancreatic cancer (Hermann et al. J Exp Med 218:e20210911, 2021). Within this project they plan to investigates the cause of sex-specific TIMP-1 gene expression using suitable genetically modifies cell culture systems, mouse models combined with a broad spectrum of molecular-biochemical as well as in silico methods, also in cooperation with different partner labs.
If you have an M.Sc. in biochemistry, biology, molecular biotechnology or similar, and would like to work towards a PhD or Dr. rer. nat., please contact Prof. Krüger here.
Krüger Lab employs a wide spectrum of technologies encompassing all aspects of molecular cloning/genetic engineering, expression-vector design, biochemistry, cell culture including functional cell-assays, metabolic assays, protein-design and purification, flow-cytometry, histology, in silico-modeling, TIMSTOF, statistical analyses, bioinformatics etc. in order to explore the biology of TIMP-1.
Through cooperation with colleagues in the clinic they constantly validate their data with material from the clinic towards a transfer of new knowledge from bench to the bedside.
Examples of publications from our group (PhD students underlined):
- Eckfeld, C., B. Schoeps, D. Häußler, J. Frädrich, F. Bayerl, J.P. Böttcher, P. Knolle, S. Heisz, O. Prokopchuk, H. Hauner, E. Munkhbaatar, I.E. Demir, C.D. Hermann, Achim Krüger. TIMP-1 is a novel ligand of Amyloid Precursor Protein and triggers a pro-inflammatory phenotype in human monocytes. J Cell Biol 222 : e202206095, 2023.
- Schoeps, B., J. Frädrich, A. Krüger. Cut loose TIMP-1: an emerging cytokine in inflammation. Trends Cell Biol online ahead of print, 2022.
- Hermann, C.D., B. Schoeps, C. Eckfeld, E. Munkhbaatar, L. Kniep, O. Prokopchuk, N. Wirges, K. Steiger, D. Häußler, P. Knolle, E. Poulton, R. Khokha, B.T. Grünwald, I.E. Demir, A. Krüger. TIMP1 expression underlies sex-disparity in liver metastasis and survival in pancreatic cancer. J Exp Med 218 : e20210911, 2021.
- Schoeps, B., C. Eckfeld, L. Flüter, S. Keppler, R. Mishra, P. Knolle, F. Bayerl, J. Böttcher, C.D. Hermann, D. Häußler, A. Krüger. Identification of invariant chain CD74 as a functional receptor of tissue inhibitor of metalloproteinases-1 (TIMP-1). J Biol Chem 297 : 101072, 2021.
- Schoeps, B., C. Eckfeld, O. Prokopchuk, J.P. Böttcher, D. Häußler, K. Steiger, I.E. Demir, P. Knolle, O. Soehnlein, D.E. Jenne, C.D. Hermann, A. Krüger. TIMP1 triggers neutrophil extracellular trap formation in pancreatic cancer. Cancer Res 81 : 3568-3579, 2021.
- Eckfeld, C., D. Häußler, B. Schoeps, C.D. Hermann, A. Krüger. Functional disparities within the TIMP family in cancer: hints from molecular divergence. Cancer Metastasis Rev 38 : 469-481, 2019.
- Grünwald, B., B. Schoeps, A. Krüger. Recognizing the molecular multifunctionality and interactome of TIMP-1. Trends Cell Biol 29 : 6-19, 2019.
- Grünwald, B., V. Harant, S. Schaten, M. Frühschütz, R. Spallek, B. Hoechst, K. Stutzer, S. Berchtold, M. Erkan, O. Prokopchuk, M. Martignoni, I. Esposito, M. Heikenwaelder, A. Gupta, J. Siveke, P. Saftig, P.A. Knolle, D. Wohlleber, A. Krüger, Pancreatic pre-malignant lesions secrete TIMP1, which activates hepatic stellate cells via CD63 signaling to create a pre-metastatic niche in the liver. Gastroenterology 151 : 1011-1024, 2016.
Contact:
Prof. Dr. rer. nat. Achim Krüger
Klinikum rechts der Isar der TU München
Institut für Experimentelle Onkologie und Therapieforschung