Vacancies 64201-PhD-candidate-pediatric-endocrine-disease

  • 40 hours a week
  • Temporary
  • 4 years
  • Date of publication: 27 December 2018
  • Deadline: 24 January 2019
  • Scale 10A: max € 42220 gross per year at full employment (incl. vacation bonus and end of year payments)
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Job description

Congenital adrenal hyperplasia (CAH) is the most common inherited disorder affecting adrenal steroid synthesis. The clinical presentation depends on the severity of the enzyme deficiency with -in the most severe cases- complete cortisol and aldosterone deficiency causing an Addisonian crisis within the first weeks of life and prenatal virilisation of the affected females. The accumulation of steroid precursors before the enzymatic block serves as a diagnostic marker for CAH.
 
Nowadays, the diagnosis of the most severe type of CAH can be made at an early age by neonatal screening programs or by prenatal diagnosis in the case of an affected proband, thereby preventing life threatening events. Most children reach adult age without severe morbidity. However, in adult CAH patients several complications can develop and in recent years it became clear that some of them might be already detected in childhood.
 
One of the most important and frequently detected complications in male CAH patients is the development of benign testicular tumours. Although these tumours have no malignant features, , they can lead to obstruction of the seminiferous tubules leading to gonadal dysfunction and infertility because of their location in the mediastinum testis. These tumors have histological and functional features of adrenocortical cells. Therefore, they are called testicular adrenal rest tumours (TART). However, the aetiology is not yet known.
 
The current project focuses on the following aspects of congenital adrenal hyperplasia:
The first aim of this project is to study the etiological features of TART in CAH patients. The PhD candidate will perform transcriptome profiling using RNA-sequencing (RNAseq) to compare the expression profiles of pooled RNA samples of TART, with available fetal and adult normal adrenal and testis tissues. Using Ingenuity Pathway Analyses and other applicable bioinformatics analyses the PhD candidate will identify putative TART-inducing mechanisms, which will also include drugable pathways that could eventually be used for prevention of TART development.
 
The RNAseq experiment will yield valuable insights in the etiology of TART, but also provide us with suitable (bio)markers to distinguish TART from Leydig cell tumors (LCT), which is the second aim of this project. Sometimes TART is diagnosed as LCT, which is more aggressively treated. The PhD candidate will use immunohistochemistry of new TART-specific markers obtained in the first aim, to prevent overtreatment of undiagnosed TART.
 
Additionally, also clinical aspects of CAH will be studied:
One of the hallmarks in patients with CAH is the accumulation of adrenal steroid precursors. We recently showed that some of these precursors have glucocorticoid activity, thereby possibly partly compensating for cortisol deficiency. The PhD candidate will set up a mathematical model to predict the extent by which precursors activate the glucocorticoid receptor and preclude life-threatening adrenal crises in patients with CAH. Optimizing glucocorticoid treatment in children by studying different treatment strategies will be another part of the project.

Profile

The ideal candidate fulfils the requirements:
 
  • Master degree in Medical Biology, Molecular Life Sciences, medicine or equivalent;
  • Experience with bioinformatics, statistics, immunohistochemistry, modelling;
  • Strong motivation to succeed in scientific research;
  • Be able to work in a team;
  • Fluent in English;
  • Independent and well-structured working style.

Organization

Nijmegen is the oldest Dutch city with a rich history and one of the liveliest city centers in the Netherlands. Radboud University has over 17,000 students. Radboud university medical center (Radboudumc) is a leading academic centre for medical science, education and health care with over 10,000 staff and 3,000 students.

The project will be carried out at the department of Pediatrics, and the department of Laboratory Medicine as part of the Radboud Adrenal centre (RAC). RAC serves as a centre of expertise for the diagnosis and treatment of children and adults with adrenal diseases.

Radboudumc
Radboudumc strives to be a leading developer of sustainable, innovative and affordable healthcare to improve the health and wellbeing of people and society in the Netherlands and beyond. This is the core of our mission: To have a significant impact on healthcare. To get a better picture of what this entails, check out our strategy.

Read more about what it means to work at Radboudumc and how you can do your part.

Employment conditions

Upon commencement of employment we require a certificate of conduct (Verklaring Omtrent het Gedrag, VOG) and there will be, depending on the type of job, a screening based on the provided cv. Radboud university medical center’s HR Department will apply for this certificate on your behalf.

Read more about the Radboudumc employment conditions and what our International Office can do for you when moving to the Netherlands.

Comments and contact information

Please include a CV and the following documents in a single pdf file:
  • motivation letter
  • list of followed courses and grades
  • and preferably a copy of your Master thesis or a publication in English you have written.

All additional information about the vacancy can be obtained from dr. Hedi Claashen, children endocrinologist. Use the Apply button to submit your application.

Please apply before 24 januari.
Recruitment agencies are asked not to respond to this job posting.

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