Congenital adrenal hyperplasia (CAH) is a rare group of diseases of the adrenal cortex characterized by impaired cortisol production and accumulation of precursors steroids (PS) and adrenal androgens (AA). The CAH research group aims to personalize and improve treatment of patients to avoid over- and undertreatment. Are you the PhD candidate to help us reach our goals? We would like to get to know you!

In this project we will focus on patients with CAH due to 21-hydroylase deficiency, the most common form of CAH with a prevalence of 1:15 000. Patients require lifelong cortisol replacement treatment based on international guidelines, yet most adult patients develop short- and long-term complications. Patients are at risk to develop a life threatening adrenal crisis in situations of illness. Therefore, parents and patients have to be educated regularly to increase their cortisol dosages adequately in situations of stress. Well-known long-term complications in undertreated patients with chronically elevated AA are infertility, cardiovascular, and metabolic diseases with a reduced quality of life. In overtreated patients, adrenal androgens are suppressed but the high cortisol doses commonly lead to obesity, hypertension, and other metabolic symptoms. The dose of cortisol necessary to normalize AA levels is highly variable (between 8-17 mg/m2 /day). This may be explained by interindividual variability in glucocorticoid receptor sensitivity (GRS). As this receptor conveys cortisol signals, inter-patient differences in GRS are hypothesized to lead to large variances in treatment effects and toxicity. Moreover, the modulating effects of the CAH disease itself and/or its treatment on GRS are not established.

We hypothesize that CAH patients show variable treatment responses as PS, AA, and glucocorticoid treatment all may have different influences on glucocorticoid receptor activity (GRA). A better understanding of factors influencing GRS in CAH patients will help personalizing and improving treatment to avoid over- and undertreatment. To allow comprehend examination of factors influencing GRS as well as GRA in general we will use a novel zebrafish model to gather mechanistical insights behind GRA and GRS in 21OHD-deficient zebrafish mutants as model for CAH patients. The zebrafish is a comprehensive in vivo model organism for studying adrenal steroid hormone biosynthesis and GRS under different circumstances. Furthermore, ex vivo qualification of GRS variations in human
patient and healthy control cells will be performed to establish clinical relevance of the data. The GRS in CAH patients and healthy volunteers will be investigated using an ex vivo peripheral blood mononuclear cells (PBMC) model.

Tasks and responsibilities

• Unravelling the influence of precursors steroids and receptor sensitivity in CAH
  disease using zebrafish and ex vivo PBMC model.
• Optimalization of treatment regimen for CAH patients.
• Correlation obtained research data with clinical data.
• Generate and critically analyze the data in order to prepare scientific publications
  and presents findings at scientific meetings.
• Supervise MSc and/or BSc students.
• Participation in the graduate school of Radboudumc.

The ideal candidate for this position holds an MSc degree in Biomedical Sciences, Molecular Life Sciences, Medicine, or a related field. A strong motivation, flexibility, and willingness to learn are essential. You have a tructured working style, a critical scientific attitude and the ability to work both independently and in a group. Furthermore you have excellent communication skills in English, both oral and written.

Experience in molecular and cell biology is highly valued, as is familiarity with Article 9 of the Dutch Law on Animal Experimentation. Additional points are awarded to candidates with experience in in vivo modeling using zebrafish and bioinformatics.

Fixed-term contract: 3 years.

At Radboud university medical center, you build on your future. We are committed to providing the best care, education, and research. And we are true to our word, because we help you develop and seize opportunities and give you the room to grow. As an employer, we believe that employees should feel vital and happy at work in all stages of life. We are also committed to creating a healthy and safe working environment. Our employment conditions contribute to that. What we offer:

• Upon commencement of employment, you will start at scale 10A, step 0 (€ 3.017 based on a full-time appointment). Over a maximum period of 4 years, you will progress to scale 10A, step 3 (€ 3.824 based on a full-time appointment). You will also receive an 8% vacation allowance, an 8.3% end-of-year bonus, and, depending on the position, an allowance of 47% to 72% for working irregular hours.
• Plenty of opportunities to develop yourself. For example, you can follow various courses via our online learning environment. A lot of attention will also be paid to your wellbeing and vitality. For instance, you can take advantage of:
  
  • a 40% discount on gym membership at the Radboud Sports Center.
  • the Company Support Team and a personal coach if you experience a life-changing event.
  • a financially favorable option to work less through a generation scheme if you are approaching state retirement age.
  • support with achieving a good work-life balance at every stage of your life. This includes advice and training (from ‘Millennial Dilemmas’ to ‘Your Career After 57’), activities at our own mindfulness center, and informal caregiving consultations if you have any questions about combining your work and caregiving tasks at home.
• 168 vacation hours per year based on a 36-hour working week. Want more vacation? You can buy additional vacation hours with your end-of-year bonus.
• 26 weeks of parental leave, of which 9 weeks are paid.
• Extra-favorable leave conditions. For example, our short-term caregiving leave is not 2 but 4 weeks per year and even 12 weeks per year for partner and child.
• Pension accrual with the ABP Pension Fund. Radboud university medical center pays 70% of the pension contribution.
• Discount on the supplementary packages of two collective health insurance policies and on ten other types of insurance, from home insurance to legal assistance.
• A travel allowance via our Employment Conditions Selection Model and a working-from-home allowance of €2 per day.

Radboudumc

The PhD position is available at the crossroad of fundamental and clinical research based at the department of Paediatrics at the Radboudumc, centre of expertise on Sex & Gender headed by Prof. dr. Hedi Claahsen. The research will be performed in close collaboration with the Department of Ecology and Physiology (dr. Margo Dona) at the Radboud Institute Biological and Environmental Sciences (RIBES) and the Department of Laboratory Medicine (dr. Teun van Herwaarden, Prof. Fred Sweep). You will join the Congenital Adrenal Hyperplasia (CAH) research group, with a longstanding experience of investigating
pathophysiological mechanisms of CAH steroidogenesis.

Radboudumc
Welcome to Radboud university medical center (Radboudumc), where scientific breakthroughs are born through the curiosity and passion of our collaborating researchers in a vibrant environment. We believe trust and excitement are crucial elements to achieving our goals, and we approach our research as teams and with the utmost rigor to make a significant impact on health and healthcare. Our researchers are driven by their fascination with the biological, psychological, and sociological mechanisms underlying health and healthcare. They collaborate with partners from all over the world to improve health outcomes for all. Radboudumc unites patient care, research, education, and corporate learning, which allows us to approach our mission to shape the health and healthcare of the future in an innovative and person-centered way.

Our ambition is to lead the way in the pursuit of prevention, sustainability, meaningful care. We believe that through our research, we can significantly improve the health and well-being of society. Join us on our mission to make a difference in healthcare. Become a part of our community of gifted researchers, professionals or patient partners who are dedicated to making a real impact on population health and healthcare.

Read what it is like to do a PhD at the Radboud University Medical Center.

Any questions? Or wondering what it is like to work at Radboudumc? Then call, send a message or email to Margo Dona, Post-doc, at (+31) 6 12 82 69 01. Alternatively, you can contact Hedi Claahsen, at
(+31) 24 361 44 30 or Teun van Herwaarden, laboratory specialist, at (+31) 6 22 39 73 26. Use the Apply button to submit your application.