Dr Kai Erdmann
Room: C09 Addison building
Brief career history
Membrane trafficking and signalling in polarised cells. Role of multi-PDZ domain proteins in cancer formation, metastasis and tumor invasion
Biochemical and mechanochemical mechanisms of epithelial cell polarisation
Undergraduate and postgraduate taught modules
Postgraduate PhD Opportunities
1. Establishment of an in vitro model for cystic fibrosis using organ on chip technology
Cystic fibrosis is a devastating disease affecting the lung and the intestine. Cystic fibrosis is a genetic disease and caused by mutations of the chloride channel CFTR (cystic fibrosis transmembrane conductance regulator). Major phenotypes are increased mucus production in the lung causing extreme breathing difficulties as well as defective signaling in the intestine. One in three thousand newborns are affected.
The goal of this PhD project is the establishment of a state of the art in vitro model for cystic fibrosis to study the disease mechanism in more detail but also to establish a model suitable for high-throughput drug screening. The project will make use of modern organ on chip technology, which allows the functional reconstitution of organ functionality in miniaturized microfluidic devises. Precisely we will apply devices to mimic blood and airflow of the lung allowing a more physiological model system than just 2 or 3D cell cultures.
The aims of this project are
Techniques: CRISPR-technology, organoids, 3D cell cultures with different mechanical properties, micro-molding using soft-litography, Micropatterning, siRNA-technology, Cell imaging (live confocal spinning disk and super-resolution microscopy, Total-internal reflection microscopy)
2. The role of multi-PDZ domain proteins in the regulation of epithelial cell proliferation and cancer
PTPN13 is a highly modular multi-PDZ domain protein composed of an N-terminal KIND (Kinase non catalytic C-lobe) domain, followed by a FERM (Four-point-one/Ezrin/Radixin/Moesin) domain, five PDZ domains, and a tyrosine phosphatase domain assembling a large macromolecular protein complex. There is strong evidence that PTPN13 plays a role in tumor development. In a search for protein tyrosine phosphatases involved in formation of colon carcinoma, it was demonstrated that PTPN13 is mutated in around 10% of colon carcinomas. We have recently identified novel components of the PTPN13 complex. This complex plays an important role in the regulation of cell/cell adhesion and nuclear transcription. However, the precise molecular mechanism, how PTPN13 contributes to tumor development is largely unclear
The goal of this project is to investigate the role of PTPN13 and other multi-PDZ domain proteins in the context of contact inhibition of proliferation, metastasis and tumor invasion. We will apply in vitro cell proliferation, migration and tumor invasion assays as well as state of the art still- and live-imaging microscopy techniques (like spinning disc confocal microscopy and superresolution microscopy) to investigate underlying disease mechanisms. Furthermore, using in vitro 3-dimensional cell culture systems and modern chip based cell micropatterning we will further analyze the role and molecular mechanism of PTPN13 in epithelial cell proliferation and cell polarization.
For further information about these projects and how to apply, see our PhD Opportunities page:
- Yu F, Sharma S, Skowronek A & Erdmann KS (2016) The serologically defined colon cancer antigen-3 (SDCCAG3) is involved in the regulation of ciliogenesis. Scientific Reports, 6, 35399-35399. View this article in WRRO
- Hagemann N, Ackermann N, Christmann J, Brier S, Yu F & Erdmann KS (2012) The serologically defined colon cancer antigen-3 interacts with the protein tyrosine phosphatase PTPN13 and is involved in the regulation of cytokinesis. Oncogene.
- Hou X, Hagemann N, Schoebel S, Blankenfeldt W, Goody RS, Erdmann KS & Itzen A (2011) A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1. EMBO Journal, 30(8), 1659-1670.
- Stenzel N, Fetzer CP, Heumann R & Erdmann KS (2009) PDZ-domain-directed basolateral targeting of the peripheral membrane protein FRMPD2 in epithelial cells. Journal of Cell Science, 122(18), 3374-3384.
- Erdmann KS, Mao Y, McCrea HJ, Zoncu R, Lee S, Paradise S, Modregger J, Biemesderfer D, Toomre D & De Camilli P (2007) A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway.. Dev Cell, 13(3), 377-390.