Proyecto:
Crosstalk between heparanase, immune cells, and HPV in the pathogenesis of Head & Neck carcinoma.
Compelling evidence ties heparanase, the sole heparan sulfate (HS) degrading endoglycosidase, with all steps of tumor formation including tumor initiation, growth, metastasis, and chemo-resistance, thus encouraging the development of heparanase inhibitors as anti-cancer drugs. Mechanistic studies on heparanase action focused on its preferential expression by tumor cells. Yet, non-tumor (host) cells, including macrophages, NK cells, and T-cells, also upregulate heparanase expression upon activation and thereby affect cancer progression. In contrast, heparanase-2 (Hpa2), a close homolog of heparanase, lacks enzymatic activity, inhibits heparanase activity and regulates genes that promote normal differentiation, ER-stress, tumor fibrosis, and apoptosis, resulting in tumor suppression. Focusing on head & neck squamous cell carcinoma (HNSCC), the primary objective of the joint project is to elucidate the synergistic mechanism by which heparanase and chemotherapy affect immune cells in the tumor microenvironment and thereby the tumor aggressiveness. Given the contribution of human papillomavirus (HPV) to the etiology of HNSCC, this project will study the involvement of heparanase and HS in HPV transforming capability and the mode by which Hpa2 may suppress HPV-associated HNSCC.
Cualificación:
Master en Biología, Bioquímica, Biomedicina, Biologia Molecuar, Biotecnología o relacionados.
Oferta:
Beca para doctorado (Universidad de Heidelberg) de tres años de duración.
Contacto:
Dr. Angel Cid-Arregui
Targeted Tumor Vaccines
German Cancer Research Center (DKFZ)
Im Neuenheimer Feld 280
69120 Heidelberg
Germany
Tel: +49 6221 423714
https://www.dkfz.de/en/angewandte-tumor-immunitaet/targeted-tumor-vaccines/index.html
