The impact of hypoxia pathway proteins on the adrenergic response in the adrenal gland and beyond
Principal Investigators
Prof. Dr. med.
Ali El-Armouche
Technische Universität Dresden
Universitätsklinikum Carl Gustav Carus
Institute of Pharmacology and Toxicology
ali.el-armouche[at]tu-dresden.de
Prof. Dr., PhD
Ben Wielockx
Technische Universität Dresden
Universitätsklinikum Carl Gustav Carus
Institute of Clinical Chemistry and Laboratory Medicine
ben.wielockx[at]tu-dresden.de
Wissenschaftliche Mitarbeiter:innen
Scientific Staff
Deepika Watts – Postdoc
Mangesh Jaykar – PhD student
Anja Krüger – TA
Project Description
During the second funding period we will continue our research related to the impact of hypoxia-pathway proteins (HPPs) in the HPA axis and sympathetic and adrenal medullary systems. Based on our unique collection of adrenal gland-specific HPP transgenic mouse lines (Tab. 1) we aim to further delineate the consequences of chronically altered steroidogenesis and modified responses of chromaffin cells due to changes in the PHD-HIFα axis (Fig. 6). Addressing these complex interplays requires merging expertise in haematopoiesis, hypoxia pathways, adrenergic signalling and the adrenal gland; this will be brought together by the Wielockx group (Hypoxia-pathway proteins/ haematopoiesis/ inflammatory models), the El-Armouche group (SNS/ beta-adrenergic signalling) and the close collaborations established with a number of other groups
Aims
(I) Determine the impact of chronic exposure to systemic high/low glucocorticoid levels in adrenocortical-related HPP transgenic mice during haematopoiesis/erythropoiesis and local immune response.
(II) Characterise the consequences of modulating central HPPs in chromaffin cells in mice.
(III) Define the potential role of β2AR on haematopoietic cell lineages during (stress) haematopoiesis/erythropoiesis.
Publications
Watts, D.; Stein, J.; Meneses, A.; Bechmann, N.; Neuwirth, A.; Kaden, D.; Kruger, A.; Sinha, A.; Alexaki, V.I.; Luis Gustavo, P.-R.; Kircher, S.; Martinez, A.; Theodoropoulou, M.; Eisenhofer, G.; Peitzsch, M.; El-Armouche, A.; Chavakis, T.; Wielockx, B. HIF1alpha is a direct regulator of steroidogenesis in the adrenal gland. Cell Mol Life Sci 2021, 78, 3577-3590.
Sormendi, S.; Deygas, M.; Sinha, A.; Bernard, M.; Kruger, A.; Kourtzelis, I.; Le Lay, G.; Saez, P.J.; Gerlach, M.; Franke, K.; Meneses, A.; Krater, M.; Palladini, A.; Guck, J.; Coskun, U.; Chavakis, T.; Vargas, P.; Wielockx, B. HIF2alpha is a direct regulator of neutrophil motility. Blood 2021, 137, 3416-3427.