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Dr. Holger Becker

Dr. Holger M. Becker studied Biology at the University of Kaiserslautern, Germany, where he received his Ph.D. in 2005. Following a postdoc period in the Division for General Zoology at the University of Kaiserslautern and the School of Biochemistry & Molecular Biology at the Australian National University in Canberra, he was appointed Junior Professor for Zoology / Membrane Transport at the University of Kaiserslautern in 2009. In 2015 he completed his Habilitation in Zoology / Cell Physiology and from October 2015 until March 2016 was appointed temporary head of the Division for General Zoology at the University of Kaiserslautern. Since March 2017 he is working on a DFG-funded project entitled “Modulation of metabolite transport in human cancer cells by carbonic anhydrase” in the Institute of Physiological Chemistry at the University of Veterinary Medicine Hanover.

His research topics are focused on the regulation of acid/base-coupled metabolite transporters, with a special emphasis on the physiological and biochemical analysis of physical and functional interactions between monocarboxylate transporters and carbonic anhydrases that could form a ‘non-catalytic transport metabolon’. Besides analyzing the structural properties of these protein complexes he investigates their role in the regulation of energy metabolism in various cells and tissues. A key aspect is thereby how these transport metabolons facilitate metabolite transport and acid/base regulation in cancer cells. To realize these projects Dr. Becker uses a combination of molecular biology and biochemical techniques, like heterologous protein expression in Xenopus oocytes, site-directed mutagenesis, co-immunoprecipitation and gas-analysis mass spectrometry. Furthermore he applies different advanced microscopic techniques, including single-cell metabolite imaging with FRET-based nanosensors, pH imaging and in situ proximity ligation assays.

Publications (since 2004)

Forero-Quintero L.S., Ames S., Schneider H.-P., Thyssen A., Boone C.D., Andring J., McKenna R., Casey J.R., Deitmer J.W. & Becker H.M. (2018) Membrane-anchored carbonic anhydrase IV interacts with monocarboxylate transporters via their chaperones CD147 and GP70. J. Biol. Chem. 294:593-607

 

Hiremath S.A., Jamali S., Ames S., Deitmer J.W., Surulescu C. & Becker H.M. (2018) Modeling of pH regulation in tumor cells: Direct interaction between proton-coupled lactate transporters and cancer-associated carbonic anhydrase. Math. Biosci. Eng. 16:320-337

 

O’Rourke K.M., Johnstone E.S., Becker H.M., Pimlott S.L. & Sutherland A. (2018) Exploring the functionalisation of the thieno[2,3-d]pyrimidinedione core: Late stage access to highly substituted 5-carboxamide-6-aryl scaffolds. Tetrahedron 74:4086-4094

 

Aspatwar A., Becker H.M., Parvathaneni N.K., Hammaren M., Svorjova A., Barker H., Supuran C.T., Dubois L., Lambin P., Parikka M., Parkkila S. & Winum J.-Y. (2018) Nitroimidazole based inhibitors DTP338 and DTP348 are safe for zebrafish embryos and efficiently inhibit the activity of human CA IX in Xenopus oocytes. J. Enzyme. Inhib. Med. Chem. 33:1064-1073

 

Noor S.I., Jamali S., Ames S., Langer S., Deitmer J.W. & Becker H.M. (2018) A surface proton antenna in carbonic anhydrase II supports lactate transport in cancer cells. eLife 7:35176

 

Ames S., Pastoreková S. & Becker H.M. (2018) The proteoglycan-like domain of carbonic anhydrase IX mediates non-catalytic facilitation of lactate transport in cancer cells. Oncotarget 9:27940-27957

 

Kazokaitė J., Niemans R., Dudutienė V., Becker H.M., Leitāns J., Zubrienė A., Baranauskienė L., Gondi G., Zeidlere R., Matulienė J., Tārs K., Yaromina A., Lambin P., Duboi L.J. & Matulis D. (2018) Novel fluorinated carbonic anhydrase IX inhibitors reduce hypoxia-induced acidification and clonogenic survival of cancer cells. Oncotarget 9:26800-26816

 

Corbet C., Bastien E., Draoui N, Doix B., Mignion L., Jordan B.F., Marchand A., Vanherck J.-C., Chaltin P., Schakman O., Becker H.M., Riant O. & Feron O. (2018) Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels direct antitumor and radiosensitizing effects. Nat. Commun. 9:1208

 

Silva L.S., Poschet G., Nonnenmacher Y., Becker H.M., Sapcariu S., Gaupel A.-C., Schlotter M., Wu Y., Kneisel N., Seiffert M., Hell R., Hiller K., Lichter P. & Radlwimmer B. (2017) Branched-chain ketoacids secreted by glioblastoma cells via MCT1 modulate macrophage phenotype. EMBO Rep. 18:2172-2185

 

Forero-Quintero L.S., Deitmer J.W. & Becker H.M. (2017) Reduction of epileptiform activity in ketogenic mice: The role of monocarboxylate transporters. Sci. Rep. 7:4900

 

Deitmer J.W., Theparambil M.S., Ruminot I. & Becker H.M. (2017) Our hungry brain: Which role do glial cells play for the energy supply? Neuroforum 23:A1–A8

 

Noor S.I., Pouyssegur J., Deitmer J.W. & Becker H.M. (2017) Integration of a ‘proton antenna’ facilitates transport activity of the monocarboxylate transporter MCT4. FEBS J. 284:149-162

 

Kazokaite J., Ames S., Becker H.M., Deitmer J.W., Matulis D. (2016) Selective inhibition of human carbonic anhydrase IX in Xenopus oocytes and MDA-MB-231 breast cancer cells. J. Enzyme. Inhib. Med. Chem. 31-38-44

 

Wandernoth P.M., Mannowetz N., Szczyrba J., Grannemann L., Wolf A., Becker H.M., Sly W.S. & Wennemuth G. (2015) Normal Fertility Requires Expression of Carbonic Anhydrases II and IV in Sperm. J. Biol. Chem. 290:29202-16

 

Klier M., Jamali S., Ames S., Schneider H.-P., Becker H.M. & Deitmer J.W. (2015) Catalytic activity of human carbonic anhydrase isoform IX is displayed extra- and intracellularly. FEBS J. 283:191-200

 

Valdebenito R., Ruminot I., Garrido-Gerter P., Fernández-Moncada I., Forero-Quintero L., Alegría K., Becker H.M., Deitmer J.W. & Barros L.F. (2015) Targeting of astrocytic glucose metabolism by beta-hydroxybutyrate. J. Cereb. Blood Flow Metab. 36:1813-1822

 

Jamali S., Klier M., Ames S., Barros L.F., McKenna R., Deitmer J.W. & Becker H.M. (2015) Hypoxia-induced carbonic anhydrase IX facilitates lactate flux in human breast cancer cells by non-catalytic function. Sci. Rep. 5:13605

 

Heidtmann H., Ruminot I, Becker H.M. & Deitmer J.W. (2015) Inhibition of monocarboxylate transporter by N-cyanosulphonamide S0859. Eur. J. Pharmacol. 5:344-9

 

Noor S.I., Dietz S., Heidtmann H., Boone C.D., McKenna R., Deitmer J.W. & Becker H.M.* (2015) Analysis of the Binding Moiety mediating the Interaction between Monocarboxylate Transporters and Carbonic Anhydrase II. J. Biol. Chem. 290:4476-86

 

Hemme D., Surulescu C., Becker H.M., Deitmer J.W., Mühlhaus T., Garth C. & Schroda M. (2015) BioComp – complex data analysis in sciences and biotechnology. Systembiologie.de 9:68-71

 

Deitmer J.W., Theparambil S.M., Ruminot I. & Becker H.M. (2014) The role of membrane acid/base transporters and carbonic anhydrases for cellular pH and metabolic processes. Front. Neurosci. 8:430

 

Becker H.M. (2014) Transport of Lactate: Characterization of the Transporters Involved in Transport at the Plasma Membrane by Heterologous Protein Expression in Xenopus Oocytes. Neuromethods: Brain Energy Metabolism. 80:25-43

 

Peetz J., Barros L.F., San Martín A. & Becker H.M. (2014) Functional interaction between bicarbonate transporters and carbonic anhydrase modulates lactate uptake into mouse cardiomyocytes. Pflügers Arch. 467:1469-80

 

Becker H.M., Klier M. & Deitmer J.W. (2014) Carbonic anhydrases and their interplay with acid/base-coupled membrane transporters. Subcell. Biochem. 75:105-34

 

Klier M., Andes F.T., Deitmer J.W. & Becker H.M. (2013) Intracellular and Extracellular Carbonic Anhydrases Cooperate Non-Enzymatically to Enhance Activity of Monocarboxylate Transporters. J. Biol. Chem. 289:2765-75.

 

Deitmer J.W. & Becker H.M. (2013) Transport metabolons with carbonic anhydrases. Front. Physiol. 4:291

 

Bonar P., Schneider H.P., Becker H.M., Deitmer J.W. & Casey J.R. (2013) Three-Dimensional Model for the Human Cl-/HCO3- Exchanger, AE1, by Homology to the E. coli ClC Protein. J. Mol. Biol. 425:2591-608.

 

Schneider H.P., Alt M.D., Klier M., Spiess A., Andes F.T., Waheed A., Sly W.S., Becker H.M. & Deitmer J.W. (2013) GPI-anchored carbonic anhydrase IV displays both intra- and extracellular activity in cRNA-injected oocytes and in mouse neurons. Proc. Natl. Acad. Sci. U. S. A. 110:1494-9

 

Stridh M.H., Alt M.D., Wittmann S., Heidtmann H., Aggarwal M., Riederer B., Seidler U., Wennemuth G., McKenna R., Deitmer J.W. & Becker H.M. (2012) Lactate flux in astrocytes is enhanced by a non-catalytic action of carbonic anhydrase II. J. Physiol. 590:2333-51

 

Schueler C., Becker H.M., McKenna R. & Deitmer J.W. (2011) Transport activity of the sodium bicarbonate cotransporter NBCe1 is enhanced by different isoforms of carbonic anhydrase. PLoS One. 6:e27167.

 

Klier M., Schüler C., Halestrap A.P., Sly W.S., Deitmer J.W. & Becker H.M. (2011) Transport Activity of the High-affinity Monocarboxylate Transporter MCT2 Is Enhanced by Extracellular Carbonic Anhydrase IV but Not by Intracellular Carbonic Anhydrase II. J. Biol. Chem.  286:27781-27791.

 

Becker H.M., Klier M., Schüler C., McKenna R. & Deitmer J.W. (2011) Intramolecular proton shuttle supports not only catalytic but also noncatalytic function of carbonic anhydrase II. Proc. Natl. Acad. Sci. U. S. A. 108:3071-6

 

Wandernoth P.M., Raubuch M., Mannowetz N., Becker H.M., Deitmer J.W., Sly W.S., Wennemuth G. (2010) Role of carbonic anhydrase IV in the bicarbonate-mediated activation of murine and human sperm. PLoS One 5:e15061.

 

Becker H.M., Klier M. & Deitmer, J.W. (2010) Nonenzymatic augmentation of lactate transport via monocarboxylate transporter isoform 4 by carbonic anhydrase II. J. Membr. Biol. 232(4):125-135

 

Becker H.M. & Deitmer J.W. (2008) Non-enzymatic proton handling by carbonic anhydrase II during H+-lactate cotransport via monocarboxylate transporter 1. J. Biol. Chem. 283:21655-21667

 

Wendel C., Becker H.M. & Deitmer J.W. (2008) The sodium-bicarbonate cotransporter NBCe1 supports glutamine efflux via SNAT3 (SLC38A3) co-expressed in Xenopus oocytes. Pflügers Arch. 455:885-93

 

Becker H.M. & Deitmer J.W. (2007) Carbonic anhydrase II increases the activity of the human electrogenic Na+/HCO3- cotransporter. J. Biol. Chem. 282:13508-21

 

Weise A., Becker H.M. & Deitmer J.W. (2007) Enzymatic suppression of the membrane conductance associated with the glutamine transporter SNAT3 expressed in Xenopus oocytes by carbonic anhydrase II. J. Gen. Physiol. 130:203-15

 

Becker H.M., Hirnet D., Fecher-Trost C., Sültemeyer D. & Deitmer J.W. (2005) Transport activity of MCT1 expressed in Xenopus oocytes is increased by interaction with carbonic anhydrase. J. Biol. Chem. 280:39882-39889

 

Becker H.M. & Deitmer J.W. (2004) Voltage dependence of H+ buffering mediated by sodium bicarbonate cotransport expressed in Xenopus oocytes. J. Biol. Chem. 279:28057-62

 

Becker H.M., Bröer S. & Deitmer J.W. (2004) Facilitated lactate transport by MCT1 when coexpressed with the sodium bicarbonate cotransporter (NBC) in Xenopus oocytes. Biophys. J. 86:235-247

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