Function description
The Netherlands Cancer Institute (NKI)
Located in Amsterdam, NKI is an internationally renowned institute dedicated to fundamental, translational and clinical cancer research, and the only comprehensive cancer center in The Netherlands. It is a dynamic institute accommodating over 50 research groups and many advanced core facilities, including flow cytometry, proteomics, genomics, biobank and a mouse cancer center.
Project information
The Peeper lab uses functional oncogenomic and other advanced technology to combat immunotherapy resistance. The introduction of immune checkpoint antibodies and other therapies like TIL and CAR-T cells 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. 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.
Located in Amsterdam, NKI is an internationally renowned institute dedicated to fundamental, translational and clinical cancer research, and the only comprehensive cancer center in The Netherlands. It is a dynamic institute accommodating over 50 research groups and many advanced core facilities, including flow cytometry, proteomics, genomics, biobank and a mouse cancer center.
Project information
The Peeper lab uses functional oncogenomic and other advanced technology to combat immunotherapy resistance. The introduction of immune checkpoint antibodies and other therapies like TIL and CAR-T cells 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. 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.
Job requirements
An ambitious technician with mouse model experience.
We seek an enthusiastic and accurate animal technician. It is strictly necessary that you hold a license for
working with laboratory animals (art. 6/9/12). You should also have expertise in immunology
and/or molecular biology. You will be responsible for carrying out animal experiments in
collaboration with researchers on this project. Furthermore, you will contribute to wet-lab
experiments and some lab management tasks. Proficiency in English and good communicative
skills are important requirements, as is a team player mentality.
We seek an enthusiastic and accurate animal technician. It is strictly necessary that you hold a license for
working with laboratory animals (art. 6/9/12). You should also have expertise in immunology
and/or molecular biology. You will be responsible for carrying out animal experiments in
collaboration with researchers on this project. Furthermore, you will contribute to wet-lab
experiments and some lab management tasks. Proficiency in English and good communicative
skills are important requirements, as is a team player mentality.
Compensation
The vacancy is available this Fall.
You will be employed for a minimum period of 2 years, with the possibility for extension. The gross
salary per month can range from € 2.682,- to € 3.642,- (salary scale 45 according to the
Collective Labour Agreement General Hospitals based on proven qualifications). In addition,
you will receive 8,33% holiday pay and end-of-year bonus (8,33%).
Interested?
For further information and applications, please visit:
https://www.nki.nl/research/research-groups/daniel-peeper/.
Applications should include your CV, a motivation letter and references. Apply by the 'Apply now' button at the bottom of the page.
Select reading
- Zhang et al, RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive
immune cells, Cell Reports Medicine 2022
- Apriamashvili et al, Ubiquitin ligase STUB1 destabilizes IFNγ-receptor complex to suppress
tumor IFNγ signaling, Nature Comm 2022
- Vredevoogd et al, The (re)discovery of tumor-intrinsic determinants of immune sensitivity by
functional genetic screens, IOTech 2022
- Vredevoogd et al., Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity
Threshold, Cell 2019
The NKI values diversity and is committed to creating an inclusive work environment that stimulates the best in each individual. Applications of all individuals are welcomed regardless of age, ancestry, religion, disability, distance from the labor market, sexual orientation or gender identity.
You will be employed for a minimum period of 2 years, with the possibility for extension. The gross
salary per month can range from € 2.682,- to € 3.642,- (salary scale 45 according to the
Collective Labour Agreement General Hospitals based on proven qualifications). In addition,
you will receive 8,33% holiday pay and end-of-year bonus (8,33%).
Interested?
For further information and applications, please visit:
https://www.nki.nl/research/research-groups/daniel-peeper/.
Applications should include your CV, a motivation letter and references. Apply by the 'Apply now' button at the bottom of the page.
Select reading
- Zhang et al, RNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive
immune cells, Cell Reports Medicine 2022
- Apriamashvili et al, Ubiquitin ligase STUB1 destabilizes IFNγ-receptor complex to suppress
tumor IFNγ signaling, Nature Comm 2022
- Vredevoogd et al, The (re)discovery of tumor-intrinsic determinants of immune sensitivity by
functional genetic screens, IOTech 2022
- Vredevoogd et al., Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity
Threshold, Cell 2019
The NKI values diversity and is committed to creating an inclusive work environment that stimulates the best in each individual. Applications of all individuals are welcomed regardless of age, ancestry, religion, disability, distance from the labor market, sexual orientation or gender identity.
Details
- Hours per week: 36
- Salary level: FWG 45
Mylene van der Velden
