PhD student at the Leiden / Amsterdam Center for Drug Research
- Specifications - (explanation)
Location Gorlaeus laboratories Einsteinweg 55 2333 CC Leiden Function types PhD positions Scientific fields Natural Sciences, Health Hours 38.0 hours per week Salary maximum € 2612 Education University Graduate Job number 12-179 Translations en
Job description
The
project is funded by a Dutch Cancer Foundation (KWF) and is entitled
‘Novel Protein Kinases Targets In IGF-1 and EGF Receptor - Mediated
Drug Resistant Breast Cancer’.
Treatment of breast cancer has improved with the introduction of anti-estrogen therapy. Yet a large percentage (>40%) of tamoxifen treated breast cancers eventually become resistant to tamoxifen, and also resistance to other anti-estrogens has been reported. Resistance to anti-estrogens has been linked to increased expression and/or activation of various receptor tyrosine kinases (RTKs) such as EGFR, IGF-1R and HER2. This may lead to downstream phosphorylation of the estrogen receptor and insensitivity to the antagonistic action of anti-estrogens.
We have recently established relevant models for anti-estrogen resistant breast cancer by ectopically expressing the human EGFR and IGF-1R in human MCF7 breast cancer cells. When stimulated with EGF or IGF1 respectively, these cells are almost completely resistant to inhibition of estradiol-induced cell proliferation by tamoxifen and fulvestrant. Using genome-wide protein kinase and phosphatase siRNA-based screening we identified >35 kinases and phosphatases in MCF7/IGF-1R cells that reversed the IGF1-induced tamoxifen resistance. These candidates may represent potentially novel drug targets for anti-estrogen resistant breast cancer. The goals of this project are to characterize these novel drug targets with respect to their role in tamoxifen resistance, breast cancer cell proliferation and survival in 3D models in vitro, and to validate the role of a selected number of these drug target candidates in control of cell proliferation, tamoxifen resistance, and tumor progression in vivo, in xenograft tumor models in mice.
Treatment of breast cancer has improved with the introduction of anti-estrogen therapy. Yet a large percentage (>40%) of tamoxifen treated breast cancers eventually become resistant to tamoxifen, and also resistance to other anti-estrogens has been reported. Resistance to anti-estrogens has been linked to increased expression and/or activation of various receptor tyrosine kinases (RTKs) such as EGFR, IGF-1R and HER2. This may lead to downstream phosphorylation of the estrogen receptor and insensitivity to the antagonistic action of anti-estrogens.
We have recently established relevant models for anti-estrogen resistant breast cancer by ectopically expressing the human EGFR and IGF-1R in human MCF7 breast cancer cells. When stimulated with EGF or IGF1 respectively, these cells are almost completely resistant to inhibition of estradiol-induced cell proliferation by tamoxifen and fulvestrant. Using genome-wide protein kinase and phosphatase siRNA-based screening we identified >35 kinases and phosphatases in MCF7/IGF-1R cells that reversed the IGF1-induced tamoxifen resistance. These candidates may represent potentially novel drug targets for anti-estrogen resistant breast cancer. The goals of this project are to characterize these novel drug targets with respect to their role in tamoxifen resistance, breast cancer cell proliferation and survival in 3D models in vitro, and to validate the role of a selected number of these drug target candidates in control of cell proliferation, tamoxifen resistance, and tumor progression in vivo, in xenograft tumor models in mice.
Requirements
We
seek a talented and highly motivated candidate with proven experience
in cell and molecular biology, cell signalling and light microscopy. The
candidate should have a MSc degree in (Medical) Biology, Life Science
Technology, Bio-Pharmaceutical Sciences or any other closely related
discipline. Experience or affinity with image analysis is recommended.
Conditions of employment
The
candidate will work within the Division of Toxicology and the Leiden
Cell Observatory. We are situated in the Gorlaeus Laboratories on the
Science Park Leiden. Currently, 30 researchers including technicians,
PhD students, and Postdocs work in the Division of Toxicology. The
candidate will become part of a young and dynamic team of around 30 PhD
students and postdocs with a strong expertise in and signal
transduction, breast cancer models, and live cell imaging. We offer a
vibrant, research-driven work environment with emphasis on team spirit,
excellence, and skills development.
Appointment will be according to the terms of the Collective Labour Agreement of Dutch Universities (CAO Nederlandse Universiteiten), for the duration of one year with an extension of three years after positive evaluation. The salary will be set on € 2042,- per month in the first year up to € 2612,- in year four. An appointment with Leiden University includes a pension build-up and facilitates other benefits such as an annual holiday premium of 8% and an end-of-year premium of 8.3%.
All our PhD students are embedded in the Leiden University Graduate School of Science www.graduateschools.leidenuniv.nl. Our graduate school offers several PhD training courses at three levels: professional courses, skills training and personal effectiveness. In addition, advanced courses to deepen scientific knowledge are offered though other PhD training networks.
Appointment will be according to the terms of the Collective Labour Agreement of Dutch Universities (CAO Nederlandse Universiteiten), for the duration of one year with an extension of three years after positive evaluation. The salary will be set on € 2042,- per month in the first year up to € 2612,- in year four. An appointment with Leiden University includes a pension build-up and facilitates other benefits such as an annual holiday premium of 8% and an end-of-year premium of 8.3%.
All our PhD students are embedded in the Leiden University Graduate School of Science www.graduateschools.leidenuniv.nl. Our graduate school offers several PhD training courses at three levels: professional courses, skills training and personal effectiveness. In addition, advanced courses to deepen scientific knowledge are offered though other PhD training networks.
Organisation
Leiden University
Leiden
is a typical university city, hosting the oldest university in the
Netherlands (1575). The University permeates the local surroundings;
University premises are scattered throughout the city, and the students
who live and study in Leiden give the city its relaxed yet vibrant
atmosphere.
Leiden University is one of Europe's foremost research universities. This prominent position gives our graduates a leading edge in applying for academic posts and for functions outside academia.
Leiden University is one of Europe's foremost research universities. This prominent position gives our graduates a leading edge in applying for academic posts and for functions outside academia.
Additional information
For more information, please contact Prof.dr. Bob van de Water (telephone: +31 (0)71-5276223; email: water_b@lacdr.leidenuniv.nl), or Dr. John Meerman (telephone: +31 (0)6-53970982; email: meerman@lacdr.leidenuniv.nl).
Additionally, you can visit the websites of the Division of Toxicology, the Faculty of Science, and the LACDR: toxicol.lacdr.gorlaeus.net; www.science.leidenuniv.nl; www.lacdr.nl. More information on employment at Leiden University can be found at: www.medewerkers.leidenuniv.nl; or www.leidenuniv.edu.
More information about employer
Leiden University
on AcademicTransfer.
Direct link to this job opening: www.academictransfer.com/14905Additionally, you can visit the websites of the Division of Toxicology, the Faculty of Science, and the LACDR: toxicol.lacdr.gorlaeus.net; www.science.leidenuniv.nl; www.lacdr.nl. More information on employment at Leiden University can be found at: www.medewerkers.leidenuniv.nl; or www.leidenuniv.edu.
Found here: http://www.academictransfer.com/employer/LEI/vacancy/14905/lang/en/
