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The Peeper lab uses functional oncogenomic and other advanced technology to combat immunotherapy resistance. The introduction of ICB, most commonly in the form of CTLA-4 and PD-1 antibodies but also other therapies like TIL and CAR-T, has been clinically transformative.
However, most patients fail to respond (durably), often because of upfront or acquired resistance. Several resistance mechanisms have been described, including tumor cell-intrinsic and T cell-dependent ones. To develop therapeutic solutions, it is imperative that we understand the underlying mechanisms. Furthermore, given the diversity of this problem, there is a need to find specific solutions. Here, we focus on a therapeutic strategy to break tumor cell-intrinsic immune resistance.
We have recently uncovered a critical and conserved mechanism of tumor cell-intrinsic resistance involving TNF-mediated survival signaling. By genetic screening, we discovered that ablation of TRAF2, a key TNF signal transducer sharply lowered the tumor TNF cytotoxicity threshold, thereby augmenting tumor T cell- and ICB-impact in vitro and in preclinical murine models. Furthermore, loss of TRAF2 in patient tumors increases immune sensitivity, which was independently confirmed in a large-scale genetic analysis of clinical specimens. In this project, we focus on a druggable target in this pathway that we have discovered, aiming to not only understand its mechanism of action but also to explore clinical translation.
We are seeking a highly ambitious postdoc with a strong background in molecular and/or cancer biology and immunology, experience with mouse studies, and an interest in fundamental and translational cancer research. Your responsibilities will include writing of manuscripts and grant applications. Proficiency in English and good communicative skills are important requirements, as is a team player mentality.
Fixed-term contract: Minimum of 2 years.
The vacancy is available immediately. You will be employed for a minimum period of 2 years. The gross salary per month is € 3.879 to € 4.611 according to salary scale FWG 55, depending on your experience. The terms of employment will be in accordance with FWG 55 of the CAO Ziekenhuizen (Collective Labour Agreement for Hospitals). In addition, you will receive a fixed end-of-year bonus in December (8,33%) and in May you will receive 8,33% holiday pay.
Located in Amsterdam, NKI is the only comprehensive cancer center in The Netherlands. It is a well-organized and dynamic institute accommodating over 50 research groups and many advanced core facilities. It is an internationally renowned center dedicated to fundamental, translational and clinical cancer research.
For further information and addresses visit: https://www.nki.nl/research/research-groups/daniel-peeper/.
The Netherlands Cancer Institute
Plesmanlaan 121, 1066 CX, Amsterdam
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