Group members

PD Dr. Helge Müller-Fielitz, Dr. Vanessa Neve, Dr. Akila Chandrasekar, Andreea Constaninescu

Research Interests

The group investigates the boundary-forming cells of the brain, such as brain endothelial cells and tanycytes. Special interest lies in studying the physiological role of tanycytes, a specialized population of glial cells in the ependymal layer of the 3rd ventricle. The cell bodies of tanycytes are in contact with the cerebrospinal fluid (CSF) and send long projections into the parenchyma of the basal hypothalamus and the median eminence, where they make contact with blood vessels. Tanycytes are strategically located to control the blood-CSF barrier of the median eminence, regulate the transport of substances across this barrier, and influence hormone release into the portal venous system of the median eminence.

Our main focus is to clarify the role of tanycytes in regulating energy homeostasis, barrier function, and their influence on hormone release from the hypothalamus-pituitary axis. Additionally, we are examining the significance of different neuronal populations, particularly TRH neurons, their networks, and their impact on energy metabolism.

To explore these topics, we have developed new genetic and viral tools to specifically manipulate functions in vivo. With these tools, we can knock out or overexpress genes in a cell-type-specific manner and investigate the structural and genetic consequences, as well as changes in the phenotype of the animals. For phenotypic characterization, we use indirect calorimetry, behavioral tests, hormonal assays, and single-cell analyses to characterize changes in gene expression.

This working group is part of the newly established consortium “New Methods to Investigate the Vasculature in systemic Autoimmune Diseases (MI-VascAD)” at the University of Lübeck. For details see here: https://www.mi-vascad.uni-luebeck.de/. 

Collaborations

• Rubén Nogueiras, University of Santiago, Spain
• Vincent Prévot, INARM Lille, France
• Heike Heuer, University of Essen, Germany
• Jens Mittag, University of Luebeck, Germany

Selected Publications

Fernandois D, Rusidzé M, Müller-Fielitz H, Sauve F, Deligia E, Silva MSB, Evrard F, Franco-García A, Mazur D, Martinez-Corral I, Jouy N, Rasika S, Maurage CA, Giacobini P, Nogueiras R, Dehouck B, Schwaninger M, Lenfant F, Prevot V. 2024. Estrogen receptor-α signaling in tanycytes lies at the crossroads of fertility and metabolism. Metabolism. 158:155976. 

Platzbecker K*, Müller-Fielitz H*, Foraita R, Koepp MJ, Voss A, Pflock R, Linder R, Pigeot I, Schink T, Schwaninger M. 2023. In atrial fibrillation epilepsy risk differs between oral anticoagulants: active comparator, nested case-control study. Europace. 25(5):euad087. 

Chandrasekar A, Schmidtlein PM, Neve V, Rivagorda M, Spiecker F, Gauthier K, Prevot V, Schwaninger M, Müller-Fielitz H. 2023. Regulation of Thyroid Hormone Gatekeepers by Thyrotropin in Tanycytes. Thyroid. 34(2):261-273. 

Graßhoff H, Müller-Fielitz H, Dogbevia GK, Körbelin J, Bannach J, Vahldieck CM, Kusche-Vihrog K, Jöhren O, Müller OJ, Nogueiras R, Prevot V, Schwaninger M.  2022. Short regulatory DNA sequences to target brain endothelial cells for gene therapy. J Cereb Blood Flow Metab. 42(1):104-120

Wenzel J*, Lampe J*, Müller-Fielitz H*, Schuster R, Zille M, Müller K, Krohn M, Körbelin J, Zhang L, Özorhan Ü, Neve V, Wagner JUG, Bojkova D, Shumliakivska M, Jiang Y, Fähnrich A, Ott F, Sencio V, Robil C, Pfefferle S, Sauve F, Coêlho CFF, Franz J, Spiecker F, Lembrich B, Binder S, Feller N, König P, Busch H, Collin L, Villaseñor R, Jöhren O, Altmeppen HC, Pasparakis M, Dimmeler S, Cinatl J, Püschel K, Zelic M, Ofengeim D, Stadelmann C, Trottein F, Nogueiras R, Hilgenfeld R, Glatzel M, Prevot V, Schwaninger M. 2021. The SARS-CoV-2 main protease Mpro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells. Nat Neurosci. 24(11):1522-1533. 

Müller-Fielitz H, Stahr M, Bernau M, Richter M, Abele S, Krajka V, Benzin A, Wenzel J, Kalies K, Mittag J, Heuer H, Offermanns S, Schwaninger M. 2017. Tanycytes control the hormonal output of the hypothalamic-pituitary-thyroid axis. Nat Commun. 2017 Sep 7;8(1):484. 
 

Publications in PubMed