Phd Fellowship Deciphering The Molecular

vor 2 Monaten


Nuernberg, Deutschland Universitätsklinikum Würzburg Vollzeit

**Beschreibung**:
The hypothalamic-pituitary-adrenocortical axis is activated during stress to maintain homeostasis in the body. In physiological conditions, secretion of hypothalamic corticotropin-releasing hormone is initiated by the CNS, which stimulates the anterior pituitary lobe of the pituitary to release ACTH. This in turn induces secretion of cortisol from the adrenal cortex, which itself exerts its effects by binding to intracellular glucocorticoid (GC) receptors that subsequently act as transcriptional regulators of GC responsive target genes. Cushing´s disease (CD) is a rare, but devastating endocrine disease resulting from chronic uncontrolled cortisol secretion caused by am ACTH-secreting pituitary adenoma. Patients suffer from increased morbidity (hypertension, diabetes mellitus etc.) and mortality. We identified deubiquitination as a major driver in CD (Reincke, Sbiera et al., _Nature Genetics_ 2015 and Sbiera, et al. _Neuro Oncology_ 2019). Ubiquitination, and its reverse process, deubiquitination, are the covalent attachment and, respectively, removal of the small protein modifier ubiquitin to and from a protein. Furthermore, these processes play an important role in proteasomal degradation and recycling but also in transcriptional regulation, protein trafficking and activation of kinases involved in intracellular signaling transduction.

For additional information just contact: sbiera_s(at)ukw.de or fassnacht_m(at)ukw.de
- Can we develop a human in vitro cell model to investigate the critical pathways identified in our project?
- What are the consequences of the key mutations on the anti-tumoral immune response and how can we exploit this to improve the therapeutic options for CD patients?
- Can we identify molecular therapeutic targets in aggressive CD adenomas using spatial molecular imaging and single cell sequencing?

Applicants are invited from all nationalities, with a Master's degree in genetics, immunology or biochemistry/cell biology. Severely disabled persons will be given preference if they have essentially the same aptitude, qualifications and professional performance.

PD Dr. Silviu Sbiera

Dept. of Endocrinology and Diabetes

University Hospital Würzburg

Oberdürrbacher Str. 6

97080 Würzburg

Germany

**Anschrift für Bewerbungen**:
Josef-Schneider-Straße 2
97080 Würzburg

**Informationen zur Stelle**:
Veröffentlicht

22. Februar 2023

Ort

Würzburg

Vertragsart

Befristet Teilzeit

Link zur Homepage des Krankenhaus


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