Ruprecht-Karls-Universität Heidelberg
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Enk0117 - Scientist (f/m) / PhD position
Project no:
Enk0117

Project leader:

Project supervisor:
Enk, Alexander
Lonsdorf, Anke
Application deadline:
14. Jan 2018
Start of PhD project:
1. Apr 2018

Project description:

Title:
Characterization and modulation of CC-chemokine receptor 6 (CCR6) -
mediated immunosurveillance in malignant melanoma
Summary:
Chemokines and their receptors have been implicated in the multistage process of tumor formation and metastasis in selected human cancers.
The aim of this project is to characterize CCR6/CCL20-dependent anti-tumor immune responses and to identify local immunmodulatory factors with functional relevance for CCR6/CCL20-mediated solid tumour growth and metastasis in melanoma.
The research involves cellular and molecular immunology techniques including retrovirally transduced B16/F1 melanoma cells overexpressing CCL20 to study the role of CCR6/CCL20 in tumor cell and leukocyte activation and migration in vitro and in vivo. CCR6 gene knockout mice will be used as tools to probe for the specific involvement of CCR6/CCL20 interactions in melanoma metastasis and invasiveness. Results will be validated in spontaneously arising melanomas in Ret-transgenic mice and correlated with CCR6/CCL20 expression patterns in primary human melanoma and LN metastasis with respect to disease stage and local tumor progression.
References:
• Lonsdorf AS, Kraemer BF, Fahrleitner M, Schoenberger T, Gnerlich S, Ring S, Gehring S, Schneider SW, Kruhlak 
MJ, Meuth SG, Nieswandt B, Gawaz M, Enk AH, and HF Langer. 2012. Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 mediates interaction of melanoma cells with platelets - a connection to hematogeneous metastasis. J Biol Chem 287:2168-2178.

• Hedrick MN*, Lonsdorf AS*, Shirakawa AK, Lee CCR, Liao F, Singh SP, Zhang HH, Love PE, Hwang ST, Farber JM. 2009. CCR6 is required for IL-23-induced psoriasis-like inflammation in mice. J Clin Invest 119:2317-2329. *equal contribution, alphabetical order

• Huang V, Lonsdorf AS, Fang L, Kakinuma T, Lee VC, Cha E, Zhang H, Nagao K, Zaleska M, Olszewski WL, Hwang ST. 2008. Cutting edge: rapid accumulation of epidermal CCL27 in skin-draining lymph nodes following topical application of a contact sensitizer recruits CCR10-expressing T cells. J Immunol 180:6462-6466.

• RTG 2099/1 hompage: http://www.rtg2099.de/
Methods that will be used:
• In vivo:
o working with transgenic KO mice in models of murine melanoma (lung metastasis model, lymph node metastasis model and s.c. tumor model)

• In vitro:
o in vitro luciferase imaging of primary tumor burden and metastasis in the B16 luciferase model
o flow cytometry (FACS), immunohistochemistry and RT-PCR for the analysis of immune cell infiltrates, tumor vascularisation and the predominant chemokine/CCR and cytokine profiles in primary melanoma and lymph node metastasis
o migration assays
o apoptosis and cytotoxicity assays
Cooperation partners:
• Laboratories within the GRK/RTG 2099 (homepage: http://www.rtg2099.de/) at the University of Heidelberg, the University of Mannheim and the German Cancer Research Center (DKFZ, Deutsches Krebsforschungszentrum)

• International scientific collaboration with an inter-institutional scientific faculty in London (St. John’s Institute of Dermatology, King’s College, The University of London, Queen Mary University, Cancer Research UK, LRI, ICR, UCL). The collaboration includes lab visits as well as joint workshops and conferences in London and MA/HD.

• London Project Partner: Prof. Fran Balkwill, Centre for Cancer and Inflammation, Barts Cancer Institute, London
Personal qualifications:
• We are looking for highly motivated candidates
o with strong interest in immunology and chemokine biology
o with experience in cell culture; FACS analysis and basic molecular biological techniques
o preferably with experience in working with mouse models
o qualified to communicate and perform research in English.

• We can offer you:
o a broad scientific background and
o a special and close mentoring in a
o stimulating team-work environment
o to provide intensive supervision and an excellent start for your scientific career.
Keywords:
Cytokine/chemokine biology, Melanoma, Skin immunology