Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease with notably poor prognosis, in urgent need of improved diagnostics and treatment strategies. Metastasis to the liver is the primary contributor to the dismal outcome of pancreatic cancer and most patients die of hepatic failure. A better understanding of the cell biology and metastasis mechanisms at play should provide new opportunities for improving patient care.
Patients with liver metastasis have worse 5-years survival compared to patients with lung and nodal metastasis. Despite the morphological closeness of these organs and the common infiltration of the vasculature, the extremely high frequency of liver metastasis is poorly understood. Recent studies suggest an important role for extracellular vesicle (EV)-mediated interactions between the primary and metastatic tumors and their surrounding tissues.
EVs or ‘exosomes’ have long been considered only as containers for cellular waste, but our prior studies show they drive cell-communication both within tumor cells and in tumor microenvironment (TME). Remarkably, in mouse models PDAC-derived EVs seem critical for the development of liver metastatic niches. We have been able to extend this evidence, and we hypothesize a pivotal role for EVs in PDAC metastasis expansion and reseeding. This hypothesis has major clinical implications since pharmacological inhibition of metastatic progression can enhance the efficacy of current treatments, inhibiting disease progression, and improving survival and quality-of-life of PDAC patients.
Using in vitro, ex vivo and in vivo cancer models and next generation techniques (omics and cell-specific CRISPR-Cas9 knockout), you will face the novel exciting challenges to: 1) study in detail the pro-metastatic properties of EVs study, dissecting the communication between PDAC metastatic cells and components of the metastatic niche, 2) evaluate whether specific combinations of drugs can block the pro-metastatic actions of cancer EVs in preclinical mouse models, and 3) identify circulating biomarkers to monitor tumor progression in liver metastatic sites using cancer patient plasma, with a particular focus on circulating EV-associated factors and oncogenic kinases. To achieve these goals you will be embedded in and supported by multidisciplinary research teams who bring expertise in all relevant areas.
For further information on background, research and methodologies see the key publications:
You are a highly motivated and ambitious candidate with a master degree with an interest in the tumor microenvironment dynamics. Prefer candidates who have a degree in molecular oncology, molecular biology or equivalent.
In addition you meet the following requirements:
We offer an initial contract for 12 months that will be extended (after evaluation) for another 36 months.
You will work in a collaborative project of three departments (Medical Oncology, Pathology and Surgery, PIs: Dr. E Giovannetti, Dr. R Baglio, Dr. M Pegtel and Prof. G. Kazemier), with strong international networks with Top European Institutions. Each of these departments has several PhD students, technicians and postdoctoral researchers who share their expertise and ideas in fruitful meetings.
Working at Amsterdam UMC means working in an inspiring and professional environment where developing one`s talents and academic skills are encouraged. We offer you ample opportunity for development, deepening and broadening, additional training, and a place to grow! The culture is open and collaboration generally low key. Moreover, we strive for equal opportunities for everyone. This means that there is room for everyone’s culture, origin, ideas and creativity.
For more information about this position, you can contact Elisa Giovannetti, via telephone number: 020 444 8704.
For more information about the application procedure, you can contact Brend de Jong, corporate recruiter, via telephone number: 020-4448704.
Please apply before 6-9-2021 with reference number D09.2021.00076GD via the following link: (volgt)