Research My ambition in science is to accelerate the development of therapies for currently incurable rare genetic disorders, with a particular focus on endocrinology and immunity. My team employs a multidisciplinary approach, combining human-derived samples (blood and tumor tissues) to study the immunophenotype and validate in vivo findings. We use zebrafish and mice models for whole-organism investigations and use organoids as an animal-free platform to study disease mechanisms and test novel therapeutic compounds in drug screens. This integrative approach aims to bridge the gap between fundamental science and clinical applications, driving innovations that improve patient outcomes and ultimately contributes to the development of new therapeutic solutions. Adrenal gland disorders My research primarily focuses on rare genetic disorders related to stress and immunity, particularly diseases involving adrenal gland dysfunction such as Pheochromocytomas and Paragangliomas (PPGLs) and Congenital Adrenal Hyperplasia (CAH). Rare endocrine tumors (PPGLs) Patients with mutations in the β-subunit of the succinate dehydrogenase (SDHB) have the highest risk to develop incurable metastatic phaeochromocytomas and paragangliomas (PPGLs), a rare type of neuroendocrine cancer. Progress in clinical therapy development is hindered by limited availability of suitable model systems. We generated a sdhbrmc200 zebrafish mutant using CRISPR/Cas9 genome editing and investigated the potential of zebrafish to serve as model for SDHB-associated PPGLs. The larval sdhb mutant is a suitable model to gain insights behind the pathways involved in PPGLs. Currently the larvae are used for drug screenings to be able to study different pathways as the immune system, Hypoxia Inducible Factor (HIF) pathway and epigenetics. My goal is to establish a new research pipeline using zebrafish models to enable the rapid, efficient, and accurate evaluation of both known and novel cancer therapies. Furthermore, we developed a comprehensive toolbox to detect and follow PPGL tumor growth over time in adult zebrafish. We developed a Magnetic Resonance Imaging (MRI) and Spectroscopy protocol for in vivo imaging of tumors in adult fish. In addition, different techniques are used to characterize these fish including RNA sequencing, metabolic phenotyping, LC/MS hormone measurements, histology, flow cytometry, proteomics and advanced imaging techniques. To increase the incidence of tumor formation and accelerate tumor growth we explore different aggravation strategies, i.e. radiation, hypoxia and diet alterations, to create a functional adult zebrafish tumor model for SDHB-related PPGLs. Congenital Adrenal Hyperplasia (CAH ) Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is a rare disease of the adrenal cortex characterized by impaired cortisol production and accumulation of precursors steroids (PS) and adrenal androgens (AA). Patients require lifelong cortisol replacement treatment based on international guidelines, yet most adult patients develop short- and long-term complications. 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. 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. 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. From model to patient; platform for other types of disorders The designed platform, toolbox, and techniques are not only applicable to rare cancers and adrenal gland disorders but can also be broadly utilized for investigating a wide range of other disorders. This versatile approach enables the exploration of disease mechanisms, identification of therapeutic targets, and the development of personalized treatment strategies across various medical conditions.