Position: PhD student in oncolytic virus immune-therapy
Department: Laboratory of Oncolytic Viruses Immuno-Therapeutics
Code number: 2019-0006
The German Cancer Research Center is the largest biomedical research institution in Germany. With approximately 3,000 employees, we operate an extensive scientific program in the field of cancer research.
LOVIT is a strategic alliance between the Luxembourg Institute of Health (LIH) and the German Cancer Research Center (DKFZ), established in 2017 to advance research on oncolytic virus immunotherapy. Research at LOVIT focuses on oncolytic viruses belonging to the adenovirus and parvovirus families.
We are seeking a highly motivated PhD student for our laboratory in Heidelberg to work on the research project “Enhancing the efficacy of oncolytic viruses against prostate cancer through combination therapy”.
Oncolytic virotherapy (OVT) is a promising anti-tumour therapeutic approach which uses oncolytic viruses (OVs) to specifically kill cancer cells and elicit anti-tumour immune responses (1). However, it is important to devise novel combination therapies based on OVs and other anticancer agents in order to enhance OVT potency through synergistic anticancer effects (e.g., drugs that increase viral replication, cancer cell killing and/or anticancer immune responses) and thereby improve OVT clinical outcome. This project (financed by the MOST DKFZ-Istrael Cooperational Research Program) is carried out in collaboration with the team of Prof. Eran Bacharach and Prof. Marcelo Ehrlich (Tel Aviv University, Israel). The project builds on complementary expertise, experimental models and promising (published and unpublished) results, which the two teams have gathered in the last decade by assessing the oncolytic potential of two different oncolytic viruses: rat parvovirus H-1PV (developed by the German Team) (2) and epizootic haemorrhagic disease virus (EHDV-TAU, developed by the Israeli Team).
The major goal of this project is to design novel anticancer therapies, which combine the above-mentioned viruses with epigenetic modulators such as HDAC inhibitors (3), or pro-apoptosis drugs such as BH3 mimetics (inhibitors of pro-apoptotic BCL-2 family members). As tumour model, we will use prostate cancer, which upon reaching metastatic stage lacks efficient therapeutics options.
A second important goal of this project is to study changes in protein expression and the induction of cell death, induced by the different virus-compound or virus-virus combinations; focusing specifically on roles played by signalling pathways involved in antiviral/inflammation responses, (e.g. signalling by JAK1, STAT1, STAT3, IL-6). The combination therapies will be tested in vitro and in vivo using cellular and animal models developed by the two teams. We estimate that if successful, our studies should provide pre-clinical proof(s) of concept needed to move our combination strategies into the clinic.
1. Marchini A., Scott E. M. and Rommelaere J. (2016). Overcoming Barriers in Oncolytic Virotherapy with HDAC Inhibitors and Immune Checkpoint Blockade. Viruses DOI: 10.3390/v8010009.
2. Marchini A., Bonifati S., Scott E. M., Angelova A. L. and Rommelaere J (2015). Oncolytic parvoviruses: from basic virology to clinical applications. Virology J. 12:6 DOI: 10.1186/s12985-014-0223-y.
3. Li J., Bonifati S., Hristov G., Martilla T., Valmary-Degano S., Stanzel S., , Aprahamian M., Grekova S., Raykov Z., Rommelaere J. and Marchini A. (2013). Synergistic Combination of Valproic Acid and Oncolytic Parvovirus H-1PV as a Potential Therapy against Cervical and Pancreatic Carcinomas. EMBO Mol. Med. 10:1537-1555.
- Highly motivated with a genuine passion for science and cancer research
- Great interest in oncolytic virotherapy and immunotherapy
- Goal oriented, not afraid to challenge yourself and take responsibility
- Good background in virology, molecular biology and cell biology and rejoicing in teamwork
- Excellent verbal and written English
To apply for a position please use our online application portal. Applications should include a motivation letter, CV, copy of graduation certificates with grades and contact details of two references.
- Interesting, versatile workplace
- International, attractive working environment
- Campus with modern state-of-the-art infrastructure
- Access to international research networks
- Doctoral student payment including social benefits
- Flexible working hours
- Comprehensive training and mentoring program through the Helmholtz International Graduate School
Earliest Possible Start Date: as soon as possible
Duration: The position is limited to 3 years.
Application Deadline: 01.02.2019
Dr. Antonio Marchini
Phone +49 (0)6221/42-4969
Please note that we do not accept applications submitted via email.