Immune modulation by the endothelial protein C receptor (EPCR) in cancer progression
Abstract:
The hemostatic system plays incompletely understood roles in tumor evasion and immunomodulation. This project specifically deals with the CD1d-like receptor EPCR (Procr) that is expressed by endothelial cells, macrophages and dendritic cells. We analyze tumor evasion in tumor models that recapitulate important aspects of human tumor development. The results from these studies will uncover new therapeutic approaches to interrupt immune suppressive mechanisms in the tumor microenvironment and potentially other chronic inflammatory conditions.
Principal investigators:
PD Dr. med. Claudine Graf, PhD
Centrum für Thrombose und Hämostase
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Langenbeckstraße 1, 55131 Mainz
Phone: +49 (0)6131 17-8014
E-mail: grafc@uni-mainz.de
Web: http://www.unimedizin-mainz.de/cth/professorships-work-groups/dr-graf.html?L=1
Univ.-Prof. Dr. med. Wolfram Ruf
Centrum für Thrombose und Hämostase
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Langenbeckstraße 1, 55131 Mainz
Phone: +49 (0)6131 17-8222
E-mail: ruf@uni-mainz.de
Web: http://www.unimedizin-mainz.de/cth/professorships-work-groups/prof-ruf.html?L=1
Doctoral candidates:
Sven Pagel
Jennifer Pott
Carina Santos
Project-related publications:
Gur-Cohen S, Itkin T, Chakrabarty S, Graf C, Kollet O, Ludin A, Golan K, Kalinkovich A, Ledergor G, Wong E, Niemeyer E, Porat Z, Erez A, Sagi I, Esmon CT, Ruf W*, Lapidot T* (2015) PAR1 signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells. Nature medicine 21: 1307-17 (*corresponding authors)
Schaffner F, Yokota N, Carneiro-Lobo T, Kitano M, Schaffer M, Anderson GM, Mueller BM, Esmon CT, Ruf W (2013) Endothelial protein C receptor function in murine and human breast cancer development. PloS one 8: e61071
Ruf W, Rothmeier AS, Graf C (2016) Targeting clotting proteins in cancer therapy - progress and challenges. Thrombosis research 140 Suppl 1: S1-7
Disse J, Petersen HH, Larsen KS, Persson E, Esmon N, Esmon CT, Teyton L, Petersen LC, Ruf W (2011) The endothelial protein C receptor supports tissue factor ternary coagulation initiation complex signaling through protease-activated receptors. The Journal of biological chemistry 286: 5756-67
Schaffner F, Versteeg HH, Schillert A, Yokota N, Petersen LC, Mueller BM, Ruf W. (2010) Cooperation of tissue factor cytoplasmic domain and PAR2 signaling in breast cancer development. Blood. 116:6106-13
PR6 Versteeg HH, Schaffner F, Kerver M, Petersen HH, Ahamed J, Felding-Habermann B, Takada Y, Mueller BM, Ruf W (2008) Inhibition of tissue factor signaling suppresses tumor growth. Blood 111: 190-9
Liang HP, Kerschen EJ, Hernandez I, Basu S, Zogg M, Botros F, Jia S, Hessner MJ, Griffin JH, Ruf W, Weiler H (2015) EPCR-dependent PAR2 activation by the blood coagulation initiation complex regulates LPS-triggered interferon responses in mice. Blood 125: 2845-54
Graf C, Heidel F, Tenzer S, Radsak MP, Solem FK, Britten CM, Huber C, Fischer T, Wolfel T (2007) A neoepitope generated by an FLT3 internal tandem duplication (FLT3-ITD) is recognized by leukemia-reactive autologous CD8+ T cells. Blood 109: 2985-8
Meyer RG*, Graf C*, Britten CM, Huber C, Wölfel T (2007) Rapid identification of an HLA-B*1501-restricted vaccinia peptide antigen. Vaccine 25: 4715-22 (* shared first-authorship)
Sahin U, Tureci O, Graf C, Meyer RG, Lennerz V, Britten CM, Dumrese C, Scandella E, Wolfel T, Ludewig B (2006) Rapid molecular dissection of viral and bacterial immunomes. European journal of immunology 36: 1049-57