Novel pharmacotherapies for the treatment of central TH deprivation associated with Mct8/Oatp1c1 deficiency

Prof. Dr. Paul T. Pfluger  &  PD Dr. Timo D. Müller

In this proposal we will evaluate a series of novel TH/peptide chimeras for their ability to improve brain TH deficiency associated with AHDS. Studies will include LSFM and MS-based assessment of drug BBB permeability, advanced in vitro and in vivo approaches to delineate proof-of-concept and drugability of central Mct8 deficiency and state-of-the-art genetic, microscopic, transcriptomic and proteomic approaches to further advance our knowledge on the neuronal and behavioral underpinnings underlying disturbed Mct8 expression and function.


Project Team Members

Dr. rer. nat. Sonja Schriever Postdoc (Team Pfluger) +49 89 3187 43053 This email address is being protected from spambots. You need JavaScript enabled to view it.
Anna Molenaar PhD candidate (Team Pfluger)   This email address is being protected from spambots. You need JavaScript enabled to view it.
Dr. Gandhari Maity-Kumar Postdoc (Team Müller) +49 89 3187 2163 This email address is being protected from spambots. You need JavaScript enabled to view it.
Lisa Ständer PhD candidate (Team Müller)   This email address is being protected from spambots. You need JavaScript enabled to view it.

Further Information

Homepage Team Pfluger

Homepage Team Müller 

Selected Publications

Detection and quantification of the anti-obesity drug celastrol in murine liver and brain.
Hrabě de Angelis M, Schriever SC, Kyriakou E, Sattler M, Messias AC, Schramm KW, Pfluger PT.
2020. Neurochem Int 136:104713. doi: 10.1016/j.neuint.2020.104713

Dusp8 affects hippocampal size and behavior in mice and humans.
Baumann P, Schriever SC, Kullmann S, Zimprich A, Feuchtinger A, Amarie O, Peter A, Walch A, Gailus-Durner V, Fuchs H, Hrabě de Angelis M, Wurst W, Tschöp MH, Heni M, Hölter SM, Pfluger PT.
2019. Sci Rep 9(1):19483. doi: 10.1038/s41598-019-55527-7

Physiological and Epigenetic Features of Yoyo Dieting and Weight Control.
Contreras RE, Schriever SC, Pfluger PT.
2019. Front Genet 10:1015. doi: 10.3389/fgene.2019.01015

Profound weight loss induces reactive astrogliosis in the arcuate nucleus of obese mice.
Harrison L, Pfuhlmann K, Schriever SC, Pfluger PT.
2019. Mol Metab 149-155. doi: 10.1016/j.molmet.2019.03.009

Fluorescent blood-brain-barrier tracing shows intact leptin transport in obese mice.
Harrison L, Schriever SC, Feuchtinger A, Kyriakou E, Baumann P, Pfuhlmann K, Messias AC, Walch A, Tschöp MH, Pfluger PT.
2019. Int J Obes (Lond) 43(6);1305-1318. doi: 10.1038/s41366-018-0221-z

The Scaffold Protein p62 Regulates Adaptive Thermogenesis Through ATF2 Nuclear Target Activation.
Fischer K, Fenzl A, Liu D, Dyar KA, Kleinert M, Brielmeier M, Clemmensen C, Fedl A, Finan B, Gessner A, Jastroch M, Huang J, Keipert S, Klingenspor M, Brüning JC, Kneilling M, Maier FC, Othman AE, Pichler BJ, Pramme-Steinwachs I, Sachs S, Scheideler A, Thaiss WM, Uhlenhaut H, Ussar S, Woods SC, Zorn J, Stemmer K, Collins S, Diaz-Meco M, Moscat J, Tschöp MH, Müller TD.
2020. Nat Commun 11(1):2306. doi: 10.1038/s41467-020-16230-8

Chemical Hybridization of Glucagon and Thyroid Hormone Optimizes Therapeutic Impact for Metabolic Disease.
Finan B, Clemmensen C, Zhu Z, Stemmer K, Gauthier K, Müller L, De Angelis M, Moreth K, Neff F, Perez-Tilve D, Fischer K, Lutter D, Sánchez-Garrido MA, Liu P, Tuckermann J, Malehmir M, Healy ME, Weber A, Heikenwalder M, Jastroch M, Kleinert M, Jall S, Brandt S, Flamant F, Schramm KW, Biebermann H, Döring Y, Weber C, Habegger KM, Keuper M, Gelfanov V, Liu F, Köhrle J, Rozman J, Fuchs H, Gailus-Durner V, Hrabě de Angelis M, Hofmann SM, Yang B, Tschöp MH, DiMarchi R, Müller TD.
2016. Cell 167(3):843-857.e14. doi: 10.1016/j.cell.2016.09.014

Dual melanocortin-4 Receptor and GLP-1 Receptor Agonism Amplifies Metabolic Benefits in Diet-Induced Obese Mice.
Clemmensen C, Finan B, Fischer K, Tom RZ, Legutko B, Sehrer L, Heine D, Grassl N, Meyer CW, Henderson B, Hofmann SM, Tschöp MH, Van der Ploeg LH, Müller TD.
2015. EMBO Mol Med 7(3):288-98. doi: 10.15252/emmm.201404508

GLP-1/glucagon coagonism restores leptin responsiveness in obese mice chronically maintained on an obesogenic diet.
Clemmensen C, Chabenne J, Finan B, Sullivan L, Fischer K, Küchler D, Sehrer L, Ograjsek T, Hofmann SM, Schriever SC, Pfluger PT, Pinkstaff J, Tschöp MH, Dimarchi R, Müller TD.
2014. Diabetes 63(4):1422-7. doi: 10.2337/db13-1609

The Orphan Receptor Gpr83 Regulates Systemic Energy Metabolism via Ghrelin-Dependent and Ghrelin-Independent Mechanisms.
Müller TD, Müller A, Yi CX, Habegger KM, Meyer CW, Gaylinn BD, Finan B, Heppner K, Trivedi C, Bielohuby M, Abplanalp W, Meyer F, Piechowski CL, Pratzka J, Stemmer K, Holland J, Hembree J, Bhardwaj N, Raver C, Ottaway N, Krishna R, Sah R, Sallee FR, Woods SC, Perez-Tilve D, Bidlingmaier M, Thorner MO, Krude H, Smiley D, DiMarchi R, Hofmann S, Pfluger PT, Kleinau G, Biebermann H, Tschöp MH.
2013. Nat Commun 4:1968. doi: 10.1038/ncomms2968

p62 Links β-adrenergic Input to Mitochondrial Function and Thermogenesis.
Müller TD, Lee SJ, Jastroch M, Kabra D, Stemmer K, Aichler M, Abplanalp B, Ananthakrishnan G, Bhardwaj N, Collins S, Divanovic S, Endele M, Finan B, Gao Y, Habegger KM, Hembree J, Heppner KM, Hofmann S, Holland J, Küchler D, Kutschke M, Krishna R, Lehti M, Oelkrug R, Ottaway N, Perez-Tilve D, Raver C, Walch AK, Schriever SC, Speakman J, Tseng YH, Diaz-Meco M, Pfluger PT, Moscat J, Tschöp MH.
2013. J Clin Invest 123(1):469-78. doi: 10.1172/JCI64209