Project P15

 

Liver-specific TH activity in NAFLD and NASH

Prof. Dr. med. Joachim Spranger,  Prof. Dr. med. Frank Tacke  &  Dr. Eva K. Wirth

We aim to define the effects of local TH availability in the development and progression of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Deiodinases are key enzymes involved in the local activation and inactivation of TH. We will analyse the effect of genetic deletion and siRNA-based knockdown of deiodinases in appropriate rodent models, and study the modulation of genes implicated in local TH availability in human liver samples with different degrees of liver pathology.

alcaide 

Project Team Members

NamePositionPhoneEmail
Dr. rer. nat. Alix Bruneau Postdoc (Team Tacke)   Mail
PD Dr. med Tobias Püngel Postdoc (Team Tacke)   This email address is being protected from spambots. You need JavaScript enabled to view it.
Dr. Isabella Lurje Postdoc (Team Tacke)   This email address is being protected from spambots. You need JavaScript enabled to view it.
Dr. med. Miriam Sommer-Ballarini Clinician Scientist (Team Spranger)   This email address is being protected from spambots. You need JavaScript enabled to view it.
Dr. med. Laura Schmidt-Pennington Clinician Scientist (Team Spranger)   This email address is being protected from spambots. You need JavaScript enabled to view it.
Yingfu Chen PhD candidate (Team Wirth)   This email address is being protected from spambots. You need JavaScript enabled to view it.
Maksym Ryazantsev MD candidate (Team Wirth)   Mail
Wiebke Werner MD candidate (Team Tacke)   This email address is being protected from spambots. You need JavaScript enabled to view it.

Further Information

Homepage Team Spranger

Homepage Team Tacke

Homepage Team Wirth

Selected Publications

Neuronal effects of thyroid hormone metabolites.
Wirth EK, Meyer F.
2017 Mol Cell Endocrinol. 2017 Dec 15;458:136-142. doi: 10.1016/j.mce.2017.01.007

Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8.
Johannes J, Jayarama-Naidu R, Meyer F, Wirth EK, Schweizer U, Schomburg L, Köhrle J, Renko K.
2016. Endocrinology. Apr;157(4):1694-701. doi: 10.1210/en.2015-1933

Thyroid function is maintained despite increased oxidative stress in mice lacking selenoprotein biosynthesis in thyroid epithelial cells.
Chiu-Ugalde J, Wirth EK, Klein MO, Sapin R, Fradejas-Villar N, Renko K, Schomburg L, Köhrle J, Schweizer U.
2012. Antioxid Redox Signal.  Sep 15;17(6):902-13. doi: 10.1089/ars.2011.4055

Neuronal 3',3,5-triiodothyronine (T3) uptake and behavioral phenotype of mice deficient in Mct8, the neuronal T3 transporter mutated in Allan-Herndon-Dudley syndrome.
Wirth EK, Roth S, Blechschmidt C, Hölter SM, Becker L, Racz I, Zimmer A, Klopstock T, Gailus-Durner V, Fuchs H, Wurst W, Naumann T, Bräuer A, de Angelis MH, Köhrle J, Grüters A, Schweizer U.
2009. J Neurosci. Jul 29;29(30):9439-49. doi: 10.1523/JNEUROSCI.6055-08.2009

Distinct Housing Conditions Reveal a Major Impact of Adaptive Immunity on the Course of Obesity-Induced Type 2 Diabetes.
Sbierski-Kind J, Kath J, Brachs S, Streitz M, von Herrath MG, Kühl AA, Schmidt-Bleek K, Mai K, Spranger J, Volk HD.
2018. Front Immunol. May 28;9:1069. doi: 10.3389/fimmu.2018.01069.

An Integrated Understanding of the Molecular Mechanisms of How Adipose Tissue Metabolism Affects Long-term Body Weight Maintenance.
Mai K, Li L, Wiegand S, Brachs M, Leupelt V, Ernert A, Kühnen P, Hübner N, Robinson P, Chen W, Krude H, Spranger J.
2019. Diabetes. Jan;68(1):57-65. doi: 10.2337/db18-0440.

Inhibition of citrate cotransporter Slc13a5/mINDY by RNAi improves hepatic insulin sensitivity and prevents diet-induced non-alcoholic fatty liver disease in mice.
Brachs S, Winkel AF, Tang H, Birkenfeld AL, Brunner B, Jahn-Hofmann K, Margerie D, Ruetten H, Schmoll D, Spranger J.
2016. Mol Metab. Aug 13;5(11):1072-1082. doi: 10.1016/j.molmet.2016.08.004.

Myeloid cells in liver and bone marrow acquire a functionally distinct inflammatory phenotype during obesity-related steatohepatitis.
Krenkel O, Hundertmark J, Abdallah AT, Kohlhepp M, Puengel T, Roth T, Branco DPP, Mossanen JC, Luedde T, Trautwein C, Costa IG, Tacke F.
2020. Gut. Mar;69(3):551-563. doi: 10.1136/gutjnl-2019-318382.

Therapeutic inhibition of inflammatory monocyte recruitment reduces steatohepatitis and liver fibrosis.
Krenkel O, Puengel T, Govaere O, Abdallah AT, Mossanen JC, Kohlhepp M, Liepelt A, Lefebvre E, Luedde T, Hellerbrand C, Weiskirchen R, Longerich T, Costa IG, Anstee QM, Trautwein C, Tacke F.
2018. Hepatology. Apr;67(4):1270-1283. doi: 10.1002/hep.29544.

Liver macrophages in tissue homeostasis and disease.
Krenkel O, Tacke F. 
2017. Nat Rev Immunol. May;17(5):306-321. doi: 10.1038/nri.2017.11.