RIMLS societal impact highlights of 2019
The search to improve the conditions of CAH patients
Every day, Hedi Claahsen and her colleagues deal with unsolved clinical problems. With her research, she tries to advance medical care, improve the patients' quality of life, and prevent long-term complications.read the interview
The search to improve the conditions of CAH patientsI’ll do research as long as there are unanswered questions
Clinician and pediatric endocrinologist Hedi Claahsen has had an eventful year. Besides her ongoing research and clinical work, one of her papers published in a high-impact journal* won the Dietrich-Knorr Prize for the best-2019 paper in the field of adrenal research. With the opening of the Radboud center of expertise Sex & Gender and the hosting of the first international CAH symposium, it doesn’t seem like things are going to calm down any time soon.
You’re considered one of the leading experts in the field of Congenital Adrenal Hyperplasia. Can you briefly explain this condition and your research?
“Congenital Adrenal Hyperplasia – CAH – is a group of inherited disorders affecting the adrenal glands. The adrenal glands produce corticosteroids and sex hormones (androgens). CAH patients don’t produce enough corticosteroids, which play a role in blood sugar levels, blood pressure, and the immune system. Due to a lack of the cortisol driven negative feedback system, the adrenal glands are continuously stimulated, becoming bigger (hyperplastic) and produce high amounts of adrenal sex hormones. In female CAH patients, the elevated androgens lead to prenatal virilization of the external genitalia. With medication like hydrocortisone, the missing corticosteroids can be replaced, and androgen production will be suppressed."
“One of my research themes is long-term complications in CAH patients. Male CAH patients have a high risk for infertility due to the presence of benign tumors growing in the testes. These tumors are known as testicular adrenal rest tumors, also known as TARTs. We discovered that these tumors seem to have features of the adrenal gland tissue. Our current study also shows testicular features. We, therefore, hypothesize that TARTs consist of more totipotent cells, such as embryological tissue. Now, our research focuses on the cause of tumor growth. This knowledge will hopefully help to develop medication to treat or prevent TART and, consequently, improve fertility."
“Another research line is carried out in close collaboration with Dr. Agustini Utari from Diponegoro University in Semarang, Indonesia. In Indonesia, medication, such as hydrocortisone, is not readily available. We know that untreated patients with adrenal diseases and cortisol deficiency have a high mortality rate. However, we observed that some CAH patients with severe cortisol deficiency still survive without medication. How is this possible, we wondered? We were able to show that these patients do have deficient cortisol production but strongly elevated precursor hormones that typically accumulate in CAH patients. Our in vitro studies showed that these precursors have similar cortisol activity on the glucocorticoid receptor and may probably partly compensate for the lack of cortisol. We still collaborate with Indonesia and hope to learn more about the natural course of this disease, and to improve medical care for these patients.”
You combine clinical work with research. Was it always your ambition to do both?
“I started my career as a children’s nurse at a local hospital in Germany. But I soon realized that I wanted to learn more, so I began studying medicine in Nijmegen. After completing my medical degree, I started my training as a pediatrician and pediatric endocrinologist and began my clinical PhD research on TARTs."
“Every day, my colleagues and I deal with unsolved clinical problems. With my research, I try to advance medical care, improve my patients' quality of life, and prevent long-term complications. As long as there are unanswered questions, there’s a reason to continue our research."
You have two exciting events coming up: the opening of the center of expertise Sex & Gender and an international symposium. Can you tell us a little about them?
“I’ve been the coordinator of the Radboud DSD center – Disorders/differences of Sex Development – for several years now. There’s a considerable waiting list for transgender patients. Our center has a highly dedicated DSD team, which consists of, for example, specialized nurses, endocrinologists, psychologists, and urologists. We realized they all have the necessary knowledge needed to offer transgender care. So, we decided to expand the center to Sex & Gender. I want the center not only to be a clinic where we help patients individually but also where we can pursue interesting new research themes as many transgender-related questions are still unsolved."
“Officially, the Radboud expertise center Sex & Gender will open in March 2020. With a skilled multidisciplinary team, we’ll offer highly specialized care and guidance to people with gender dysphoria. But, of course, we’ll continue our current care for people with variations in sex development.
“In October 2020, Radboud University will host the first international CAH symposium. I'm very excited to chair this symposium. Experts from all over the world accepted our invitation to come to Nijmegen and to discuss their current research in the field of CAH."
“The involvement of patients is important in both my clinical work and my research. For the implementation of the center and the upcoming symposium, we asked for input from patient organizations. They give us their views on varying aspects of our clinical care and our research questions. We also ask them to give their views on our grant proposals. I think this collaboration is one of our strengths. In March, our team will organize the annual CAH-day for the fifteenth time. Our patients and families get the opportunity to meet and to learn about the latest news in CAH care and research. It's an event we enjoy; and we get a lot of positive feedback and suggestions."
You sound extremely busy. How do you do it all?
“My days are certainly full. But my enthusiasm drives me. I enjoy my work every day. And working with my team and within my networks is a great pleasure for me."
"Of course, nothing's self-evident; I manage a lot of tasks myself. For example, I sometimes work deep into the night, writing a grant proposal. I also take the initiative for new endeavors. I like approaching people, and I've found that I'll always meet professionals who want to discover what we can achieve for our patients together."
*Journal of Clinical Endocrinology & Metabolism
Patient first? in cell biological researchIn the summer of 2018 Alessandra Cambi (cell biologist) and Gert Olthuis (medical ethicist) were invited to give a joint talk to honor Ms. Jopie Verhoeven who retired as a chair of the Patient Advisory Council of the Radboudumc. Their discussions led to an article in Trends in Cell Biology. Its abstract: “Cell biological research investigates mechanisms of health and disease, with patients as the initial motivation and ultimate target. While increasingly visible in clinical research, patient participation in cell biological research remains limited. Here we discuss key ethical issues inherent in this development and the value of building trust and trustworthiness.”
Olthuis G, Cambi A. Patient Trust and Participation. Trends Cell Biol. 29, 765-767, 2019.
ENABLE where science and society meetsOne of the main goals of ENABLE, as well as of our New Frontiers organization, is to bring science closer to society through a series of educational activities that were held across Nijmegen. The outreach activities took place on the days prior to the symposium (10-12 November 2019) and on the first day of the symposium. The activities were specifically tailored towards the young and old members of our society.
Activities for schools
To give young students a glance into biomedical research, PhD candidates of RIMLS visited a primary school and reconstructed the lab environment in a classroom. The students got their first-hand experience on the work of a scientist and they playfully learned about the various functions of the different organs in the human body. Additionally, high school students came to RIMLS to dive deeper in biomedical sciences. They joined an interactive tour to the Museum of Anatomy and Pathology, saw how scientists perform animal experiments in the imaging center PRIME, and found out how they study organs, such as the placenta, in a laboratory. Students had a chance to meet with RIMLS professionals (professors, PhD candidates, postdocs, technicians and medical students), and ask them any questions about a career in biomedicine.
Interactive session at an elderly home
RIMLS professor of Cell Biology, Alessandra Cambi, gave a lecture entitled “50 Years of Biomedical Research: What have we achieved?” in one of Nijmegen’s retirement homes. Alessandra explained how medical practice and science itself have changed in recent history – and discussed these changes with a generation that has witnessed them first-hand. Her story gave the listener a glimpse of all four ENABLE themes: Personalized Medicine, Advanced Imaging, Big Data and Fundamental Research.
Together with the International Science Film Festival InScience and the DNA-dialoog initiative, a public debate about ethical aspects of germline modification of the human genome was organized, entitled: “Baby Construction Site: Working on the DNA of Future Generations”. Science communicator Frank Kupper led the discussion between a biomedical geneticist (Marc van Mil), a medical ethicist (Eline Bunnik) and a health scientist (Ivy van Dijke). The event was articulated around a spoken word performance by Lev Avitan, and short animations prepared by DNA-dialoog.
On Wednesday evening, four bars in the city center of Nijmegen hosted a series of pub talks performed by international PhD candidates and postdocs taking part in the ENABLE conference. These young scientists shared their work with a lay audience in a short, entertaining and easy-to-grasp manner. In each of the bars, the public chose the best performance that was awarded with a prize.
At the RIMLS, we feel it is important to bring researchers and the general public in close contact. Therefore, we are very content with the successful public outreach activities and look forward to our next public event.
See here the after event movie of the whole enable event.
Science challenge at high schoolInternational PhD candidates Joshua Gillard, Dorien Feyaerts and Yessica Alina Rodriguez Rosales (themes Infectious diseases and global health and Inflammatory diseases), developed and implemented an exciting 4-day science challenge to teach vaccinology, immunology, and programming at the Lorenz Lyceum high school in Arnhem.
Focus on personalized healthcare at summerschoolResearchers from Center for Molecular and Biomolecular Informatics (CMBI), Translational Metabolic Laboratory (TML) and Human Genetics organized a successful summerschool on “Integrative X-omics analyses empowering personalized healthcare”.
The course coordinators Alain van Gool and Peter-Bram ‘t Hoen look back at an exciting week, in which 20 participants from all over Europe convened for a week full of lectures, practicals, and labtours. The week started with an introduction into biomarkers for personalized healthcare by Alain van Gool (Mitochondrial diseases). Marcel Nelen introduced them into novel genomics technologies, and Hans Wessels and Jolein Gloerich (Mitochondrial diseases) did the same for novel proteomics technologies. Peter-Bram ‘t Hoen presented a range of X-omics data integration strategies. Other topics like metabolomics, methylation and network-based data integration were covered by external speakers from the Netherlands X-omics Initiative.
Throughout the week, the participants worked on an assignment for which they needed to design a X-omics study, and define a data analysis and management plan. The participants worked in multidisciplinary teams of four. Their different scientific backgrounds helped to address this assignment from different angles. On Friday, the participants presented their exciting studies covering a range of different topics: from the study of the influence of microbiome on constipation in Parkinson's disease, to the identification of early marker signals for infection in rheumatoid arthritis patients after treatment with tocublizimab, risk assessment in prostate cancer based on combined imaging and -omics profiling, the molecular mechanisms of non-alcoholic fatty liver disease, and the early detection of cerebral course of disease in X-linked adrenoleukodystrophy.
The organizers are looking forward to the next edition coming year.