UK : PhD student preclinical research focused on research related to tumour acidosis

MAASTRO clinic

MAASTRO Lab is a basic and translational research laboratory embedded within the GROW research

institute of the Faculty of Health, Medicine and Life Sciences at Maastricht University. Research

carried out in the past has been focused on the tumour microenvironment and EGFR signaling,

pathways of relevance to radiation oncology. MAASTRO Lab has made several important

discoveries in these fields, including demonstration that EGFR is up regulated by radiation and that

hypoxia inhibits the initiation step of mRNA translation. In addition, we have initiated translational

and clinical studies based on these results including both phase I novel treatment and molecular

imaging trials as well as a Biobank project with more than 1500 patients included.

The lab has four permanent scientists, 5 technicians, more than 5 PhD students and is fully

equipped for cell culture, molecular and cellular biology (e.g. flow cytometry, hypoxia, gene

expression, proteomics and microscopy) and working with animals (optical imager, small animal

irradiator, MRI 7 Tesla and micro-PET). MAASTRO lab has set up the necessary infrastructure for

controlled exposures to hypoxia and hypoxia/reoxygenation, including development of novel

equipment that allows rapid and controlled changes in oxygenation. Access to expertise, equipment

and resources within the much larger GROW research institute and other facilities in the University

are also readily available, including the genome centre, advanced microscopy, and the animal

facility. MAASTRO has a structural collaboration with the VU in Amsterdam on molecular PET

biomarkers, with the TU/Eindhoven on Systems Biology and a close collaboration with the

University of Toronto on research related to the Unfolded Protein Response and tumour hypoxia.

The extracellular pH of solid tumours is significantly more acidic then that of normal tissues.

Hypoxia plays an important role in tumour acidity since it allows selection of cells able to

survive a hypoxic environment with the production of acid. Hypoxia unregulated genes (CA

IX, MCT-4, NHE-1,…) are responsible for extrusion of these acids towards the extracellular

microenvironment. Acidity has been shown to have a role in resistance to chemotherapy

(impaired uptake weakly basic cytostatics), proliferation and metastatic behavior.

Furthermore, it has been demonstrated that tumour alkalinisation may represent a key target

for successful future antitumor treatments.

MAASTRO lab has a vacancy for a:

PhD student in preclinical research focused on research related to tumour

acidosis (M/F)

In this position you will carry basic and/or translational research focused on research

related to tumour acidosis. You will pursue the research program on tumour microenvironment

together with Prof. Lambin, the leader of the project group. The basic hypothesis of this

project is that tumour acidosis could be a therapeutically interesting target and manipulating

it by either genetic modification or drugs can improve therapeutic efficacy. You will participate

in research within MAASTRO, the research institute GROW and the faculty of Health, Medicine

and Life Sciences. There are also possibilities to be involved in phase 1 -2 clinical trials on the

same topic. Your work will involve development of genetic models to modify the extracellular

acidosis. Furthermore, pharmaceutical compounds inhibiting pumps and exchangers involved

in the acid-base homeostasis will be investigated for their effect on antitumor treatment.

Acidosis will be evaluated using in vitro (FACS) or in vivo non-invasive (optical, MRS,…)

imaging using several animal and tumour models.

We are looking for a candidate with a master’s degree in molecular/cell biology or

Biomedical Technology. Experience and affinity for preclinical research and in vivo work is highly

valued. Authorization to work with animals in the Netherlands (art 9 certificate, The

Netherlands) and authorization to work with radioactivity (“Stralingshygiëne Niv 5b”, The Netherlands) is a plus but is not a prerequisite. We are looking for a positively minded

scientist motivated to learn new approaches and ready to work hard to build a scientific

career.

Further information will be gladly given by ludwig.dubois@maastro.unimaas.nl or Philippe

Lambin, professor of Radiation Oncology (e-mail: philippe.lambin@maastro.nl ) or telephone

number: +31-(0)88-4455666. Please also visit www.maastro.nl and www.grow-um.nl.

Your application letter, Curriculum Vitae and listing of publications can be sent before

the 15 of November 2009 to the attention of ludwig.dubois@maastro.unimaas.nl.