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Roussa Group

Prof. Dr. med. dent. Eleni Roussa

Department of Molecular Embryology

Institute of Anatomy and Cell Biology

Albertstr. 17

79104 Freiburg

Tel: 0761 2035114

Lab: 0761 2035070

Email: eleni.roussa@anat.uni-freiburg.de

Website: Prof. Dr. Roussa

PhD and post-doc positions available.

Current Research

 

In our lab we have been working on the molecular characterization of acid-base transporters involved in intracellular pH regulation and bicarbonate transport in epithelial and neural cells. The current focus of the laboratory is to understand how ionic (H+, HCO3- and Cl-) homeostasis is established and maintained in several cell types in physiological and pathophysiological conditions. We are asking how key acid-base transport proteins, such as the electrogenic Na+/HCO3- cotransporter (NBCe1) and the vacuolar H+-ATPase (V-ATPase) and Cl- transporters (K+/Cl-cotransporter 2 (KCC2) and Na+/K+/2Cl- cotransporter 1 (NKCC1) are regulated in health and disease (epilepsy, metabolic acidosis and alkalosis). Our current research addresses the molecular and functional characterization of the regulatory mechanisms in neurons, astrocytes, and epithelial cells in response to pathologic stimuli. Experimental models used include in vitro (acute slices, primary mouse hippocampal neuronal cultures, primary mouse cortical and hippocampal astrocyte cultures, and cell lines) and in vivo (conditional knock out animals, null mutant mice, transgenic mice) systems. Experimental approaches are multidisciplinary and range from cell biological, to biochemical, molecular and functional procedures.

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From Khakipoor et al., Glia, 65:1361 - 1375, 2017

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From Schrödl-Häußel et al., Glia, 63:1226 - 1239, 2015

Current projects include:

  • Interplay between transforming growth factor beta (TGF-β), and ionic homeostasis in neural cells

  • Protein / bicarbonate transport proteins and pathongenesis of epilepsy

  • Chloride homeostasis and its importance in the development and function of neural networks

  • Regulation of acid base transport proteins in epithelia and neural cells

  • Acid base homeostasis and its importance for the pathogenesis of salivary gland and kidney disease

 

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 From Kluge et al., J Cell Physiol, 2019, in press

 

Selected Publications:

Kluge M, Namkoong E, Khakipoor S, Park K, Roussa E (2019). Differential regulation of vacuolar H+-ATPase subunits by Transforming Growth Factor beta 1 (TGF-β1) in salivary ducts. J Cell Physiol in press.

Khakipoor S, Ophoven C, Schrödl-Häußel M, Feuerstein M, Heimrich B, Deitmer JW, Roussa E (2017). TGF-β signaling directly regulates transcription and functional expression of the electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), via Smad4 in mouse astrocytes. Glia 65:1361-1375. 

Roussa E, Speer JM, Chudotvorova I, Khakipoor S, Smirnov S, Rivera C, Krieglstein K (2016). The membrane trafficking and functionality of the K+-Cl- co-transporter KCC2 is regulated by TGF-β2. J Cell Sci 129:3485-3498.
 
Schrödl-Häußel M, Theparambil SM, Deitmer JW, Roussa E (2015). Regulation of functional expression of the electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), in mouse astrocytes. Glia 63:1226-1239.
 
Oehlke O, Speer JM, Roussa E (2013). Variants of the electrogenic sodium bicarbonate cotransporter 1 (NBCe1) in mouse hippocampal neurons are regulated by extracellular pH changes: evidence for a Rab8a-dependent mechanism. Int J Biochem Cell Biol. 45:1427-1438.
 
Oehlke O, Schlosshardt C, Feuerstein M, Roussa E (2012). Acidosis-induced V-ATPase trafficking in salivary ducts is initiated by cAMP/PKA/CREB pathway via regulation of Rab11b expression. Int J Biochem Cell Biol. 44:1254-1265.

Roussa E (2011). Channels and transporters in salivary glands. Cell Tissue Res. 343:263-287.

Oehlke O, Martin HW, Osterberg N, Roussa E (2011). Rab11b and its effector Rip11 regulate the acidosis-induced traffic of V-ATPase in salivary ducts. J Cell Physiol. 226:638-651.

Soyfoo MS, Bulur N, Virreira M, Louchami K, Lybaert P, Crutzen R, Perret J, Delporte C, Roussa E, Thevenod F, Best L, Yates AP, Malaisse WJ, Sener A, Beauwens R (2009). Expression of the electrogenic Na+-HCO3--cotransporters NBCe1-A and NBCe1-B in rat pancreatic islet cells. Endocrine. 35:449-458.

Brandes A, Oehlke O, Schümann A, Heidrich S, Thévenod F, Roussa E (2008) Differential regulation of SLC4A4 splice variants, NBCe1-A and NBCe1-B, in striated ducts of rat salivary glands and renal proximal tubule during acid-base disturbances. Am J Physiol Regul Integr Comp Physiol 293:R2400-2411.

Rickmann M, Orlowski B, Heupel K, Roussa E (2007) Distinct expression and subcellular localization patterns of Na+-HCO3- cotransporter (SLC4A4) variants NBCe1-A and NBCe1-B in mouse brain. Neuroscience 146:1220-1231.

Oehlke O, Sprysch P, Rickmann M, Roussa E (2006) Na+/H+ exchanger isoforms are differentially regulated in rat submandibular gland during acid/base disturbances in vivo. Cell Tissue Res 323:253-262.

Roussa E, Nastainczyk W, Thévenod F (2004) Differential expression of electrogenic NBC1 (SLC4A4) variants in rat kidney and pancreas. Biochem Biophys Res Commun 14:382-389

Thévenod F, Roussa E, Schmitt BM, Romero MF (1999) Cloning and immunolocalization of a rat pancreatic Na+ Bicarbonate Cotransporter. Biochemical and Biophysical research Communications 264:291-298.

Roussa E, Romero MF, Schmitt BM, Boron WF, Alper SL, Thévenod F (1999) Immunolocalization of anion exchanger AE2 and Na+-HCO3- cotransporter (NBC) in rat parotid and submandibular glands. American Journal of Physiology 277,G1288-G1296.

Roussa E, Alper SL, Thévenod F (2001) Immunolocalization of anionexchanger AE2, Na+/H+ exchangers NHE1 and NHE4, and vacuolar type H+-ATPase in rat pancreas. Journal of Histochemistry and Cytochemistry 49:463-474.

Development of serotonergic neurons

Cell and neuron subpopulations in the CNS differentiate in stereotypic, defined positions along the anterior-posterior and dorso-ventral axes of the neural tube and exhibit a cell-type-specific transcriptional code. Among ventral neuronal subpopulations, serotonergic (5-HT) neurons are of particular interest, because of their involvement in neurological diseases. Dysfunction of the serotonergic system is related with depression, obsessive-compulsive disorder, and schizophrenia. In our lab we have been working on the impact of Transforming growth factor beta (TGF-β) and sonic hedgehog (SHH) in the induction, differentiation and survival of neuronal subpopulations. We apply in vitro approaches (neurosphere cultures; primary neuronal cultures) from embryonic brain and in vivo models by generating mouse mutants to elucidate the underlying molecular mechanisms.  

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From Feuerstein et al., Cell Tissue Res 370:211 - 225, 2017

 

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From Chleilat et al., Neuroscience, 381:124 - 137, 2018

 

Selected Publications:

Chleilat E, Skatulla L, Rahhal B, Hussein MT, Feuerstein M, Krieglstein K, Roussa E (2018). TGF-β Signaling Regulates Development of Midbrain Dopaminergic and Hindbrain Serotonergic Neuron Subgroups. Neuroscience. 381:124-137.

Feuerstein M, Chleilat E, Khakipoor S, Michailidis K, Ophoven C, Roussa E (2017). Expression patterns of key Sonic Hedgehog signaling pathway components in the developing and adult mouse midbrain and in the MN9D cell line. Cell Tissue Res. 370:211-225.

Sharaf A, Rahhal B, Spittau B, Roussa E. Localization of reelin signaling pathway components in murine midbrain and striatum (2015). Cell Tissue Res. 359:393-407.
Osterberg, N., Roussa, E., (2009) Characterization of primary neurospheres generated from mouse ventral rostral hindbrain. Cell Tissue Res. 336: 11-20.

Roussa, E., Oehlke, O., Rahhal, B., Heermann S., Heidrich, S., Wiehle M., Krieglstein, K. (2008) TGFβ co-operates with Persephin for dopaminergic phenotype induction. Stem Cells; 26: 1683-1694.

Roussa, E., Wiehle M., Dünker N, Becker-Katins S., Oehlke O., Krieglstein, K., (2006) TGF-β is required for differentiation of mouse mesencephalic progenitors into dopaminergic neurons in vitro and in vivo. Ectopic induction in dorsal mesencephalon. Stem cells 24: 2120-2129.

Roussa, E., Farkas L., Krieglstein, K. (2004) TGF-beta promotes survival on mesencephalic dopaminergic neurons in cooperation with Shh and FGF-8. Neurobiol Dis 16:300-310.

Roussa, E., Krieglstein, K. (2004) GDNF promotes neuronal differentiation and dopaminergic development of mouse mesencephalic neurospheres. Neuroscie Let 361:52-55.

Roussa E., Krieglstein, K., (2004) Induction and specification of dopaminergic cells development: focus on TGF-β, Shh and FGF8. Cell Tissue Res 318: 23-33.

Group members

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Current lab members:

Marina Giannaki

Christian Ophoven

Melanie Feuerstein

 

Former lab members:

Dr. Shokoufeh Khakipoor

Dr. Milena Kluge

Dr. Magdalena Schrödl-Häußel

Dr. Jan Speer

Dr. Dr. Oliver Oehlke

Enaam Chleilat

Konstantinos Michailidis