Projekt A09

Hier sollte ein Bild von Stephan Herzig und Henriette Uhlenhaut, Projekt A09, SFB/TRR 205 zu sehen sein.


Prof. Dr. rer. nat. Stephan Herzig
stephan.herzig[at]helmholtz-muenchen.de
Institute for Diabetes and Cancer (IDC)
Endocrinology and Molecular Biology
Helmholtz Zentrum München (HMGU)

Prof. Dr. rer. nat. Henriette Uhlenhaut
Henriette.uhlenhaut@tum.de
Chair of Metabolic Programming
TUM School of Life Sciences Weihenstephan
ZIEL-Institute for Food & Health
Institute for Diabetes and Endocrinology (IDE)
Helmholtz Zentrum München (HMGU)

Scientific Staff:


Nina Henriette Uhlenhaut – PI
Celine Jouffe – Postdoc
Aikaterini Mechtidou – PhD

Project Description:


Project A09 deals with the over-activation of adrenal function and glucocorticoid (GC) signaling which lead to severe metabolic complications. As major effectors of the adrenal gland, GCs are essential regulators of physiology and metabolism. GCs have been shown to affect males and females differently in both rodent studies and clinical settings. Our project aims to identify the molecular and epigenetic mechanisms underlying the sexually dimorphic response to adrenal steroids observed in rodents and humans. Using total RNASeq and ChIPseq profiling, we plan to identify metabolic GC-driven, sexually dimorphic regulators both at the miRNA and the transcription factor binding level. By modulating these identified effectors of the hypothalamic-pituitary-adrenal (HPA) axis, we hope to contribute to ameliorating symptoms of GC excess, which may be more pronounced or frequent in one sex.

Sexual dimorphism of adrenal hormone action in metabolic tissues


(I) Define and functionally evaluate adrenal steroid-driven, sexually dimorphic microRNAs in adipose tissue

(II) Map genome-wide sex-specific chromatin binding by Glucocorticoid Receptor (GR) to identify co-regulators relaying adrenal signals

PhD/MD-Thesis:


Aikaterini Mechtidou: ‘Chromatin modifiers mediating genomic GR actions’; PhD thesis started fall 2017


Publications:

Glantschnig C, Koenen M, Gil-Lozano M, Karbiener M, Pickrahn I, Williams-Dautovich J, Patel R, Cummins CL, Giroud M, Hartleben G, Vogl E, Blüher M, Tuckermann J, Uhlenhaut H, Herzig S, Scheideler M. A miR-29a-driven negative feedback loop regulates peripheral glucocorticoid receptor signaling. FASEB J. 2019; 33: 5924–41.


Glantschnig C, Mattijssen F, Vogl ES, Khan AA, Garcia MR, Fischer K, Müller T, Uhlenhaut H, Nawroth P, Scheideler M, Rose AJ, Pellegata N, Herzig S. The glucocorticoid receptor in brown adipocytes is dispensable for the systemic control of energy homeostasis through brown adipose tissue. EMBO Rep.
Rose AJ, Herzig S. Metabolic control through glucocorticoid hormones: An update. Mol. Cell. Endocrinol. 2013; 380: 65–78.


Greulich F, Hemmer MC, Rollins DA, Rogatsky I, Uhlenhaut NH. There goes the neighborhood: Assembly of transcriptional complexes during the regulation of metabolism and inflammation by the glucocorticoid receptor. Steroids, 2016.


De Guia RM, Rose AJ, Sommerfeld A, Seibert O, Strzoda D, Zota A, Feuchter Y, Krones-Herzig A, Sijmonsma T, Kirilov M, Sticht C, Dallinga-thie G, Diederichs S, Klöting N, Blüher M, Diaz B, Herzig S. microRNA-379 couples glucocorticoid hormones to dysfunctional lipid homeostasis. EMBO J. 2014; 34: 1–17.


Quagliarini F, Mir AA, Balazs K, Wierer M, Dyar KA, Jouffe C, Makris K, Hawe J, Heinig M, Filipp FV, Barish GD, Uhlenhaut NH. Cistromic Reprogramming of the Diurnal Glucocorticoid Hormone Response by High-Fat Diet. Mol. Cell 2019; 76: 531-545.e5.


Hemmer MC, Wierer M, Schachtrup K, Downes M, Hübner N, Evans RM, Uhlenhaut NH. E47 modulates hepatic glucocorticoid action. Nat. Commun. 2019; 10: 306.


Greulich F, Mechtidou A, Horn T, Uhlenhaut NH. Protocol for using heterologous spike-ins to normalize for technical variation in chromatin immunoprecipitation. STAR Protoc. 2021;2(3):100609. Published 2021 Jun 16.


Greulich F, Wierer M, Mechtidou A, Gonzalez-Garcia O, Uhlenhaut NH. The glucocorticoid receptor recruits the COMPASS complex to regulate inflammatory transcription at macrophage enhancers. Cell Rep. 2021;34(6):108742.