Immunmetabolism

Head: Dr. rer. nat. Katrin Palumbo-Zerr / Dr. rer. nat. Carina Scherbel (formerly Scholtysek)

In our group we focus on intracellular metabolism in relation with the dynamics and functions of immune and bone cells. Since metabolic reprogramming and altered bioenergetics are now identified as hallmarks during the onset of inflammation as well as bone destruction, we put a special emphasis to identify novel targets of immunmetabolic checkpoints in the crosstalk of epigenetic reprogramming and cell metabolism.

  • Dissecting the immunmetabolic response of macrophages during the clearance of apoptotic cells and the resolution of inflammation

The clearance of apoptotic cells (ACs) by macrophages (MФs) promotes a profound anti-inflammatory reprogramming of these phagocytes and thereby enables the resolution of inflammation and the restoration of tissue homeostasis. The molecular mechanisms that regulate this pro-resolving switch of MФs have remain largely unclear, but essentially contributes to the resolution of inflammation.
In our project, we focus on identifying novel modulators that contribute to these metabolic and epigentic changes in MФs. Cellular metabolism and the epigenome interact with one another in a bidirectional manner, thus we aim to better understand the underlying mechanisms and to determine its relevance for the resolution of inflammation and human disease. 

  • Understanding the metabolic-epigenetic crosstalk during osteoclastogenesis and bone turnover

Osteoclasts play key roles in the regulation of bone mass and excessive osteoclastogenesis is involved in various pathologies including osteoporosis or joint destruction in autoimmune arthritis. While the molecular events priming osteoclast differentiation and activation have been extensively studied, the knowledge on cellular metabolism and its impact on OC function remain limited.
In this project, we aim to create a bioenergetic map to decipher the metabolic dynamics during osteoclastogenesis and to identify novel regulators of bone turnover. Since changes in cellular metabolism and chromatin remodelling mutually influence each other, we will put a special emphasis on the crosstalk between metabolism and changes in the epigenetic profile of osteoclast and osteoclast-mediated bone turnover.

Katrin Palumbo-ZerrJunior Research group leader
Carina Scherbel (née Scholtsek)Junior Research group leader
Rossella MancusoMedical technical assistant
Thea Hofmann 

Deutsche Forschungsgemeinschaft (DFG)
Single application “The role of caspase activation in the regulation of osteoclast fusion and bone homeostasis" (2019-2023) - Dr. Carina Scherbel

 

  1. Faas M, Ipseiz N, Ackermann J, Culemann S, Grüneboom A, Schröder F, Rothe T, Scholtysek C, Eberhardt M, Böttcher M, Kirchner P, Stoll C, Ekici A, Fuchs M, Kunz M, Weigmann B, Wirtz S, Lang R, Hofmann J, Vera J, Voehringer D, Michelucci A, Mougiakakos D, Uderhardt S, Schett G, Krönke G. (2021) IL-33-induced metabolic reprogramming controls the differentiation of alternatively activated macrophages and the resolution of inflammation. Immunity. 54(11):2531-2546.e5.
  2. Müller DIH, Stoll C, Palumbo-Zerr K, Böhm C, Krishnacoumar B, Ipseiz N, Taubmann J, Zimmermann M, Böttcher M, Mougiakakos D, Tuckermann J, Djouad F, Schett G, Scholtysek C, Krönke G. (2020) PPARδ-mediated mitochondrial rewiring of osteoblasts determines bone mass. Sci Rep. 10(1):8428.
  3. Taubmann J, Krishnacoumar B, Böhm C, Faas M, Müller DIH, Adam S, Stoll C, Böttcher M, Mougiakakos D, Sonnewald U, Hofmann J, Schett G, Krönke G, Scholtysek C. (2020) Metabolic reprogramming of osteoclasts represents a therapeutic target during the treatment of osteoporosis. Sci Rep. 10(1):21020.
  4. Brunner JS, Vulliard L, Hofmann M, Kieler M, Lercher A, Vogel A, Russier M, Brüggenthies JB, Kerndl M, Saferding V, Niederreiter B, Junza A, Frauenstein A, Scholtysek C, Mikami Y, Klavins K, Krönke G, Bergthaler A, O'Shea JJ, Weichhart T, Meissner F, Smolen JS, Cheng P, Yanes O, Menche J, Murray PJ, Sharif O, Blüml S, Schabbauer G. (2020) Environmental arginine controls multinuclear giant cell metabolism and formation. Nat Commun. 11(1):431.
  5. Scholtysek C, Ipseiz N, Böhm C, Krishnacoumar B, Stenzel M, Czerwinski T, Palumbo-Zerr K, Rothe T, Weidner D, Klej A, Stoll C, Distler J, Tuckermann J, Herrmann M, Fabry B, Goldmann WH, Schett G, Krönke G. (2018) NR4A1 Regulates Motility of Osteoclast Precursors and Serves as Target for the  Modulation of Systemic Bone Turnover. J Bone Miner Res. 33(11):2035-2047.
  6. Palumbo-Zerr K, Soare A, Zerr P, Liebl A, Mancuso R, Tomcik M, Sumova B, Dees C, Chen CW, Wohlfahrt T, Mallano T, Distler A, Ramming A, Gelse K, Mihai C, Distler O, Schett G, Distler JH. (2017) Composition of TWIST1 dimers regulates fibroblast activation and tissue fibrosis. Ann Rheum Dis. 76(1):244-251.
  7. Mallano T, Palumbo-Zerr K, Zerr P, Ramming A, Zeller B, Beyer C, Dees C, Huang J, Hai T, Distler O, Schett G, Distler JH. (2016) Activating transcription factor 3 regulates canonical TGFβ signalling in systemic sclerosis. Ann Rheum Dis. 75(3):586-92.
  8. Palumbo-Zerr K, Zerr P, Distler A, Fliehr J, Mancuso R, Huang J, Mielenz D, Tomcik M, Fürnrohr BG, Scholtysek C, Dees C, Beyer C, Krönke G, Metzger D, Distler O, Schett G, Distler JH. (2015)Orphan nuclear receptor NR4A1 regulates transforming growth factor-β signaling and fibrosis. Nat Med. 21(2):150-8.
  9. Palumbo-Zerr K, Horn A, Distler A, Zerr P, Dees C, Beyer C, Selvi E, Cravatt BF, Distler O, Schett G, Distler JH. (2012) Inactivation of fatty acid amide hydrolase exacerbates experimental fibrosis by enhanced endocannabinoid-mediated activation of CB1. Ann Rheum Dis. 71(12):2051-4.
  10. Scholtysek C, Katzenbeisser J, Fu H, Uderhardt S, Ipseiz N, Stoll C, Zaiss MM, Stock M, Donhauser L, Böhm C, Kleyer A, Hess A, Engelke K, David JP, Djouad F, Tuckermann JP, Desvergne B, Schett G, Krönke G. (2013) PPARβ/δ governs Wnt signaling and bone turnover. Nat Med. 19(5):608-13.