Projekt A02

The impact of hypoxia pathway proteins on the adrenergic response in the adrenal gland and beyond 

Hier sollte ein Bild von Ali El-Armouche und Ben Wielockx, Projekt A02, SFB/TRR 205 zu sehen sein.

Prof. Dr. Ben Wielockx, PhD
ben.wielockx(at)tu-dresden.de
Institute of Clinical Chemistry and Laboratory Medicine
University Hospital Carl Gustav Carus
Technische Universität Dresden

Prof. Dr. med. Ali El-Armouche
ali.el-armouche(at)tu-dresden.de
Institute of Pharmacology and Toxicology
University Hospital Carl Gustav
Technische Universität Dresden


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

  1. 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.
  2. 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.
  3. Watts, D.; Gaete, D.; Rodriguez, D.; Hoogewijs, D.; Rauner, M.; Sormendi, S.; Wielockx, B. Hypoxia Pathway Proteins are Master Regulators of Erythropoiesis. Int J Mol Sci 2020, 21.
  4. Watts, D.; Bechmann, N.; Meneses, A.; Poutakidou, I.K.; Kaden, D.; Conrad, C.; Krüger, A.; Stein, J.; El-Armouche, A.; Chavakis, T.; Eisenhofer, G.; Peitzsch, M.; Wielockx, B. Hypoxia pathway proteins regulate the synthesis and release of epinephrine in the mouse adrenal gland. bioRxiv 2020, doi.org/ 10.1101/2020.10.15.340943.
  5. Saadatmand, A.R.; Sramek, V.; Weber, S.; Finke, D.; Dewenter, M.; Sticht, C.; Gretz, N.; Wustemann, T.; Hagenmueller, M.; Kuenzel, S.R.; Meyer-Roxlau, S.; Kramer, M.; Sossalla, S.; Lehmann, L.H.; Kammerer, S.; Backs, J.; El-Armouche, A. CaM kinase II regulates cardiac hemoglobin expression through histone phosphorylation upon sympathetic activation. Proc Natl Acad Sci U S A 2019, 116, 22282-22287.
  6. Wielockx, B.; Grinenko, T.; Mirtschink, P.; Chavakis, T. Hypoxia Pathway Proteins in Normal and Malignant Hematopoiesis. Cells 2019, 8.
  7. Bechmann, N.; Watts, D.; Steenblock, C.; Wallace, P.W.; Schurmann, A.; Bornstein, S.R.; Wielockx, B.; Eisenhofer, G.; Peitzsch, M. Adrenal Hormone Interactions and Metabolism: A Single Sample Multi-Omics Approach. Horm Metab Res 2021, 53, 326-334.
  8. Singh, R.P.; Grinenko, T.; Ramasz, B.; Franke, K.; Lesche, M.; Dahl, A.; Gassmann, M.; Chavakis, T.; Henry, I.; Wielockx, B. Hematopoietic Stem Cells but Not Multipotent Progenitors Drive Erythropoiesis during Chronic Erythroid Stress in EPO Transgenic Mice. Stem cell reports 2018, 10, 1908-1919.