Head


Jan Peter Tuckermann
Jan Peter Tuckermann

Postdocs

Ulrike Baschant

Sabine Connert

Anna Kleyman

Kerstin Minnich

Alexander Rauch

PhD Students

Sabine Hübner

Jeanette Knoll

Sooyeon Lee

Peng Liu

Diploma Students

Frederike Kramer

Technicians

Ulrike Hillienhoff

Guests

Stefanie Rosenhain (apprentice)




Tuckermann Laboratory

Tissue-specific hormone action

Tissue specific action of glucocorticoid hormone receptors and interacting factors in age related processes: stem cell renewal / differentiation, inflammation, osteoporosis

 

    » Differential modes of glucocorticoid receptor (GR) action in the nucleus. The GR exerts in the nucleus two major types of gene regulation. 1) The GR binds as a dimer to response elements on the DNA of GC target genes and facilitates transcription by the recruitment of co-activators (p160/SRC, CBP and others, left). 2) The GR interacts with a monomer with pro-inflammatory acting transcription factors (AP-1, NF-kB, IRF-3), possibly by co-integrators such as TRIP6 or STAMP and thereby interferes with co-activator recruitment (CBP, GRIP-1 and others) important for pro-inflammatory gene expression.

Ageing of an organism is paralleled by the gradual failure and detoriation of several organs, such as the decay of muscle, bone and connective tissue, and changes in the immune system. Consequences include osteoporosis, enhanced adipogenesis, immune suppression and physiological alterations such as the metabolic syndrome. Intriguingly, pharmacologically applied glucocorticoids (GCs) exert similar catabolic effects on these organs. Thus, by understanding GC-mediated effects in organs and tissues, we may also learn about degenerative processes during ageing. Our aim is the deeper understanding of the action of GCs via their nuclear receptor (GR) in these age-related processes. We use a combinatorial approach employing functional characterization of mouse strains conditionally mutated both in the GR and selected target genes in disease models, together with the development of functional screening tools for relevant cell types in age-related disorders. Our goal is to decipher new mechanisms and to identify new mediators of therapeutic and side effects of GCs.


 

 

» Infiltrating macrophages (green) into inflamed skin in contact allergy are a target for GR activity for immune supression by GCs.

» Double calcein labelling of a vertebrae mouse bone in green fluorescence display the bone formation rate, which is inhibited by GCs via the GR in osteoblasts.

» Adipocytes labelled with Nile Red (stains lipid droplets in yellow) and DAPI (stains nuclei in blue) require the dimerized GR to promote adipogenesis.

 

Recent selected publications

  • Illing A, Liu P, Ostermay S, Schilling A, de Haan G, Krust A, Amling M, Chambon P, Schinke T, Tuckermann JP (2012) Estradiol increases hematopoietic stem and progenitor cells independent on its actions on bone. Haematologica, (epub ahead of print). [PubMed]
  • Kleiman A, Hübner S, Rodriguez Parkitna JM, Neumann A, Hofer S, Weigand MA, Bauer M, Schmid W, Schütz G, Libert C, Reichardt HM, Tuckermann JP (2012) Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages. FASEB J, 26, 722-729. [PubMed]
  • Baschant U, Frappart L, Rauchhaus U, Bruns L, Reichardt HM, Kamradt T, Bräuer R, Tuckermann JP (2011) Glucocorticoid therapy of antigen-induced arthritis depends on the dimerized glucocorticoid receptor in T cells. Proc Natl Acad Sci USA, 108, 19317-19322. [PubMed]
  • Rauch A*, Gossye, V*, Bracke, D, Gevaert, E, Jacques, P, van Bendeden K, Vandooren B, Rauner M, Hofbauer LC, Haegeman G, Elewaut D, Tuckermann JP**, De Bosscher K (2011) An anti-inflammatory selective glucocorticoid receptor modulator protects osteoblast differentiation. FASEB J, 25, 1323-3132 [PubMed]    *,**authors contributed equally    **equal correspondence
  • Tuckermann JP, Bourguet W, Mandrupp S (2010) Meeting Report: Nuclear Receptors: Transcription Factors and Drug Targets Connecting Basic Research with Translational Medicine. Mol Endocrinol, 24, 1311-1321 [PubMed]
  • Rauch A, Seitz S, Baschant, U, Schilling AF, Illing A, Stride B, Kirilov M, Mandic V, Takacz A, Schmidt-Ullrich R, Ostermay S, Schinke T, Spanbroek R, Zaiss M, Angel PE, Lerner UH, David JP, Reichard HM, Amling M, Schütz G, Tuckermann JP (2010) Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor. Cell metabolism, 8, 517-531 [PubMed]
  • Baschant U, Tuckermann JP (2010) The role of the glucocorticoid receptor in inflammation and immunity. J Steroid Biochem Mol Biol, 120, 69-75 [PubMed]
  • Chichelnitskiy E, Vegiopoulos A, Berriel Diaz M, Ziegler A, Kleiman A, Rauch A, Tuckermann JP, Herzig S (2009) In vivo PEPCK promoter mapping identifies disrupted hormonal synergism as a target of inflammation during sepsis in mice. Hepatology, 50, 1963-1971 [PubMed]
  • Tuckermann JP, Kleiman A, Moriggl R, Spanbroek R, Neumann A, Illing A, Clausen BE, Stride B, Förster I, Habenicht AJ, Reichardt HM, Tronche F, Schmid W, Schütz G (2007) Macrophages and neutrophils are the targets for immune suppression by glucocorticoids in contact allergy. J Clin Invest, 117, 1381-1390 [PubMed]

 

 

Last update: March 5, 2012
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