Your function within the department
PhD student / Postdoc position – Computational Biologist
Effect of chemo- and immunotherapy on the bladder cancer tumor-immune micro-environment
The research groups of Dr Michiel van der Heijden and Prof. dr. Lodewyk Wessels are looking for a motivated and talented Computational Biologist to join their teams at the Netherlands Cancer Institute (NKI).
Introduction of problem: Despite recent advances in treatment, and accumulating molecular knowledge of the disease, survival of patients with bladder cancer remains poor after resection. Cisplatin-based chemotherapy has a high response rate, but long-term benefit is limited. Checkpoint blockade (CPB) has shown durable remissions in the metastatic setting; its role before resection remains to be defined. Current clinical trials enroll patients without considering tumor biology, diluting clinical benefit in specific subsets of patients. We believe optimal use of currently available systemic therapies can lead to significantly higher cure rates. Our hypothesis is that there is a subset of patients in whom platinum-based chemotherapy can make the tumor-immune miroenvironment (TME) more permissive to CPB. These tumors could best be targeted by a short course of platinum-based therapy, followed by CPB. Some tumors will respond immediately to CPB, others need inhibition of additional checkpoints for a full-blown immune response, leading to sustained tumor control.
Integration of gene expression and tissue imaging to dissect the effect of systemic therapy on the TME. Over the last years, we have established a biobank of paired pre-/post-treatment tissue from 125 patients receiving systemic chemotherapy. In addition, we are conducting a unique pre-operative combination immunotherapy trial (anti-PD1 and anti-CTLA4) in bladder cancer, giving us the opportunity to study the immunological and molecular effect of these therapies in bladder cancer tissue. Pre- and on-therapy tumors will be subjected to RNA and DNA sequencing as well as spatial tissue profiling for immune markers employing the VECTRA technology. The spatial profiling provides the location of cells in a cross section of the tumor as well as the expression of the recorded markers in each cell. This allows a detailed characterization of the tumor and the surrounding stroma, indicating which immune cells are activated by therapy, their position with respect to each other and with respect to the tumor cells. The computational biologist on this project will perform (integrative) analysis of these datasets aimed at understanding the effects of systemic treatments on the bladder cancer TME and propose new therapeutic strategies to treat bladder cancer patients.
We are seeking a highly motivated candidate with:
- A degree in bioinformatics, computer science or a related discipline
- Experience with high-troughput data analysis, especially sequencing data
- Proficiency in bioinformatics programming languages (e.g. R Python)
- Good cross-disciplinary collaborative and communication skills
- Experience in statistics, machine learning and/or image processing is a plus
- Experience in cancer biology, immunology and clinical applications is a plus
Your career opportunities and terms of employment
You will join a dynamic international research group and will collaborate with scientists and clinicians with expertise in different disciplines. You will work on data from a unique set of clinical samples, at the frontier of clinical progress. Your work can have immediate impact on patient treatment. You will have the opportunity to follow high-quality courses offered: In case of a postdoc position, you will follow the NKI postdoc career development program, in case of a PhD position you will participate in the education program of the Oncology Graduate School (OOA) Amsterdam.
In case of a postdoc position, your temporary employment will be for a period of 3 years. The gross salary per month will be from € 3.363,- to € 3.774,- according to the FWG-function group 55, and depends on previous experience.
In case of a PhD position, your temporary employment will be for a period of 4 years. The gross salary per month will be from € 2.665,- € 3.282, according to the standard PhD scales.
The terms of employment will be in accordance with the CAO Ziekenhuizen (Collective Labour Agreement for Hospitals).
Amsterdam is a very livable city with many cultural amenities. The institute is located within a 20 minute tram or bicycle ride from the center of Amsterdam and within 20 minutes from Schiphol airport by car, bus or bicycle.
Please send CV and motivation letter to Michiel van der Heijden (email@example.com), Lodewyk Wessels (firstname.lastname@example.org) and Patty Lagerweij (email@example.com). Please include the names and contact information of at least two references. For further information on the Wessels group (Computational Cancer Biology) please visit our home page https://ccb.nki.nl/