Arbeitsgruppe Prof. Dr. Marc Freichel

TR-SFB 152: TRiPs to Homeostasis: Maintenance of Body Homeostasis by Transient Receptor Potential Channel Modules

http://www.sfb-trr152.med.uni-muenchen.de/index.html

SFB 1118: Reaktive Metabolite als Ursache diabetischer Folgeschäden

https://www.klinikum.uni-heidelberg.de/Willkommen.132204.0.html

FOR 2289: Calcium & Neuroinflammation

https://www.for2289.de/

DZHK

http://dzhk.de/

DFG Priority Programme 1394: Mast cells - promoters of health and modulators of disease

http://www.spp.mastzelle.de/index.php?id=24&L=1

Research Articles:

1. Lin Y, Cui X, Cao Q, Bi R, Liu Y, Jing D, Yue C, Zhao Q, Wang Y, Liu S, Su Y, Formoso K, Susperreguy S, Birnbaumer L, Freichel M, Yang Y, You L, Gao X. TRPC absence induces pro-inflammatory macrophages and gut microbe disorder, sensitizing mice to colitis. Int Immunopharmacol. 2022 Dec 31;115:109655.
2. Medert R, Thumberger T, Tavhelidse-Suck T, Hub T, Kellner T, Oguchi Y, Dlugosz S, Zimmermann F, Wittbrodt J, Freichel M. Efficient single copy integration via homology-directed repair (scHDR) by 5'modification of large DNA donor fragments in mice. Nucleic Acids Res. 2022 Dec 19:gkac1150. 
3. Yang L, Ottenheijm R, Worley P, Freichel M, Camacho Londoño JE. Reduction in SOCE and Associated Aggregation in Platelets from Mice with Platelet-Specific Deletion of Orai1. Cells. 2022 Oct 14;11(20):3225. 
4. Gegner HM, Mechtel N, Heidenreich E, Wirth A, Cortizo FG, Bennewitz K, Fleming T, Andresen C, Freichel M, Teleman AA, Kroll J, Hell R, Poschet G. Deep Metabolic Profiling Assessment of Tissue Extraction Protocols for Three Model Organisms. Front Chem. 2022 Apr 25;10:869732. 
5. Yarishkin O, Phuong TTT, Vazquez-Chona F, Bertrand J, van Battenburg-Sherwood J, Redmon SN, Rudzitis CN, Lakk M, Baumann JM, Freichel M, Hwang EM, Overby D, Križaj D. Emergent Temporal Signaling in Human Trabecular Meshwork Cells: Role of TRPV4-TRPM4 Interactions. Front Immunol. 2022 Mar 31;13:805076. 
6. Thumberger T, Tavhelidse-Suck T, Gutierrez-Triana JA, Cornean A, Medert R, Welz B, Freichel M, Wittbrodt J. Boosting targeted genome editing using the hei-tag. Elife. 2022 Mar 25;11:e70558. 
7. Gaul S, Shahzad K, Medert R, Gadi I, Mäder C, Schumacher D, Wirth A, Ambreen S, Fatima S, Boeckel JN, Khawaja H, Haas J, Brune M, Nawroth PP, Isermann B, Laufs U, Freichel M. Novel Nongenetic Murine Model of Hyperglycemia and Hyperlipidemia-Associated Aggravated Atherosclerosis. Front Cardiovasc Med. 2022 Mar 8;9:813215. 
8. Cortizo FG, Pfaff D, Wirth A, Schlotterer A, Medert R, Morgenstern J, Weber T, Hammes HP, Fleming T, Nawroth PP, Freichel M, Teleman AA. The activity of glyoxylase 1 is regulated by glucose-responsive phosphorylation on Tyr136. Mol Metab. 55:101406, 2021.
9. Schütz A, Richter C, Weissgerber P, Tsviloskyy V, Hesse M, Ottenheijm R, Zimmermann F, Buchholz S, Medert R, Dlugosz S, Kuryshev V, Benes V, Flockerzi V, Fleischmann BK, Cavalié A, Freichel M. Trophectoderm cell failure leads to peri-implantation lethality in Trpm7-deficient mouse embryos. Cell Rep. 37, 3: 109851, 2021.
10. Medert R, Bacmeister L, Segin S, Freichel M, Camacho Londoño JE. Cardiac Response to β-Adrenergic Stimulation Determined by Pressure-Volume Loop Analysis. J Vis Exp. 171: 10.3791/62057, 2021.
11. Bernal L, Sotelo-Hitschfeld P, König C, Sinica V, Wyatt A, Winter Z, Hein A, Touska F, Reinhardt S, Tragl A, Kusuda R, Wartenberg P, Sclaroff A, Pfeifer JD, Ectors F, Dahl A, Freichel M, Vlachova V, Brauchi S, Roza C, Boehm U, Clapham DE, Lennerz JK, Zimmermann K. Odontoblast TRPC5 channels signal cold pain in teeth. Sci Adv. 7,13: eabf5567, 2021.
12. Medert R, Jungmann A, Hildebrand S, Busch M, Grimm D, Flockerzi V, Müller OJ, Most P, Schumacher D, Freichel M. Development of an AAV9-RNAi-mediated silencing strategy to abrogate TRPM4 expression in the adult heart. Pflugers Arch. 473: 533-546, 2021.
13. Rosenkranz SC, Shaposhnykov AA, Träger S, Engler JB, Witte ME, Roth V, Vieira V, Paauw N, Bauer S, Schwencke-Westphal C, Schubert C, Bal LC, Schattling B, Pless O, van Horssen J, Freichel M, Friese MA. Enhancing mitochondrial activity in neurons protects against neurodegeneration in a mouse model of multiple sclerosis. Elife. 10: e61798, 2021.
14. Jeon J, Bu F, Sun G, Tian JB, Ting SM, Li J, Aronowski J, Birnbaumer L, Freichel M, Zhu MX. Contribution of TRPC Channels in Neuronal Excitotoxicity Associated With Neurodegenerative Disease and Ischemic Stroke. Front Cell Dev Biol. 8: 618663, 2021.
15. Gnad T, Navarro G, Lahesmaa M, Reverte-Salisa L, Copperi F, Cordomi A, Naumann J, Hochhäuser A, Haufs-Brusberg S, Wenzel D, Suhr F, Jespersen NZ, Scheele C, Tsvilovskyy V, Brinkmann C, Rittweger J, Dani C, Kranz M, Deuther-Conrad W, Eltzschig HK, Niemi T, Taittonen M, Brust P, Nuutila P, Pardo L, Fleischmann BK, Blüher M, Franco R, Bloch W, Virtanen KA, Pfeifer A: Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity. Cell Metab. 32: 56-70, 2020.
16. Medert R, Pironet A, Bacmeister L, Segin S, Londoño JEC, Vennekens R, Freichel M: Genetic background influences expression and function of the cation channel TRPM4 in the mouse heart. Basic Res Cardiol. 115: 70, 2020.
17. Becker A, Mannebach S, Mathar I, Weissgerber P, Freichel M, Loodin AP, Fecher-Trost C, Belkacemi A, Beck A, Philipp SE: Control of Insulin Release by Transient Receptor Potential Melastatin 3 (TRPM3) Ion Channels. Cell Physiol Biochem. 54:1115-1131, 2020.
18. Rosenkranz SC, Shaposhnykov A, Schnapauff O, Epping L, Vieira V, Heidermann K, Schattling B, Tsvilovskyy V, Liedtke W, Meuth SG, Freichel M, Gelderblom M, Friese MA: TRPV4-Mediated Regulation of the Blood Brain Barrier Is Abolished During Inflammation. Front Cell Dev Biol. 8: 849, 2020.
19. Freichel M, Ottenheijm R: L-type blocker STIMulate Ca2+ entry in synthetic VSMCs. Cell Calcium. 91: 102279, 2020.
20. Camacho Londoño JE, Kuryshev V, Zorn M, Saar K, Tian Q, Hübner N, Nawroth P, Dietrich A, Birnbaumer L, Lipp P, Dieterich C, Freichel M: Transcriptional signatures regulated by TRPC1/C4-mediated Background Ca2+ entry after pressure-overload induced cardiac remodelling. Prog Biophys Mol Biol. S0079-6107: 30071-7, 2020.
21. Hermann J, Bender M, Schumacher D, Woo MS, Shaposhnykov A, Rosenkranz SC, Kuryshev V, Meier C, Guse AH, Friese MA, Freichel M, Tsvilovskyy V: Contribution of NAADP to Glutamate-Evoked Changes in Ca2+ Homeostasis in Mouse Hippocampal Neurons.  Front Cell Dev Biol. 8: 496, 2020.
22. Weigand T, Colbatzky F, Pfeffer T, Garbade SF, Klingbeil K, Colbatzky F, Becker M, Zemva J, Bulkescher R, Schürfeld R, Thiel C, Volk N, Reuss D, Hoffmann GF, Freichel M, Hecker M, Poth T, Fleming T, Poschet G, Schmitt CP, Peters V: A Global Cndp1-Knock-Out Selectively Increases Renal Carnosine and Anserine Concentrations in an Age- and Gender-Specific Manner in Mice.  Int J Mol Sci. 21: E4887, 2020.
23. Arlt E, Fraticelli M, Tsvilovskyy V, Nadolni W, Breit A, O'Neill TJ, Resenberger S, Wennemuth G, Wahl-Schott C, Biel M, Grimm C, Freichel M, Gudermann T, Klugbauer N, Boekhoff I, Zierler S: TPC1 deficiency or blockade augments systemic anaphylaxis and mast cell activity.  Proc Natl Acad Sci U S A. 117: 18068-18078, 2020.
24. Chu WG, Wang FD, Sun ZC, Ma SB, Wang X, Han WJ, Wang F, Bai ZT, Wu SX, Freichel M, Xie RG, Luo C: TRPC1/4/5 channels contribute to morphine-induced analgesic tolerance and hyperalgesia by enhancing spinal synaptic potentiation and structural plasticity.  FASEB J. 34: 8526-8543, 2020.
25. Segin S, Berlin M, Richter C, Flockerzi RMV, Worley P, Freichel M, Londoño JEC: Cardiomyocyte-Specific Deletion of Orai1 Reveals Its Protective Role in Angiotensin-II-Induced Pathological Cardiac Remodeling.  Cells 9: 1092, 2020.
26. Formoso K, Susperreguy S, Freichel M, Birnbaumer L: RNA-seq analysis reveals TRPC genes to impact an unexpected number of metabolic and regulatory pathways.  Sci Rep. 10: 7227, 2020.
27. Tsvilovskyy V, Solis-Lopez A, Almering J, Richter C, Birnbaumer L, Dietrich A, Freichel M: Analysis of Mrgprb2 Receptor-Evoked Ca 2+ Signaling in Analysis of Mrgprb2 Receptor-Evoked Ca 2+ Signaling in Bone Marrow Derived (BMMC) and Peritoneal (PMC) Mast Cells of TRPC-Deficient Mice. Front Immunol. 11: 564, 2020.
28. Eckstein E, Pyrski M, Pinto S, Freichel M, Vennekens R, Zufall F: Cyclic regulation of Trpm4 expression in female vomeronasal neurons driven by ovarian sex hormones. Mol Cell Neurosci. 105: 103495, 2020.
29. Sanlialp A, Schumacher D, Kiper L, Varma E, Riechert E, Ho TC, Hofmann C, Kmietczyk V, Zimmermann F, Dlugosz S, Wirth A, Gorska AA, Burghaus J, Camacho Londoño JE, Katus HA, Doroudgar S, Freichel M, Völkers M: Saraf-dependent activation of mTORC1 regulates cardiac growth.  J Mol Cell Cardiol. 141: 30-42, 2020.
30. Frede W, Medert R, Poth T, Gorenflo M, Vennekens R, Freichel M, Uhl S.: TRPM4 Modulates Right Ventricular Remodeling Under Pressure Load Accompanied With Decreased Expression Level.  J Card Fail. 26: 599-609, 2020.
31. Camacho Londoño JE, Marx A, Kraft AE, Schürger A, Richter C, Dietrich A, Lipp P, Birnbaumer L, Freichel M: Angiotensin-II-Evoked Ca2+ Entry in Murine Cardiac Fibroblasts Does Not Depend on TRPC Channels. Cells 9: 322, 2020.
32. Masamune A, Kotani H, Sörgel FL, Chen JM, Hamada S, Sakaguchi R, Masson E, Nakano E, Kakuta Y, Niihori T, Funayama R, Shirota M, Hirano T, Kawamoto T, Hosokoshi A, Kume K, Unger L, Ewers M, Laumen H, Bugert P, Mori MX, Tsvilovskyy V, Weißgerber P, Kriebs U, Fecher-Trost C, Freichel M, Diakopoulos KN, Berninger A, Lesina M, Ishii K, Itoi T, Ikeura T, Okazaki K, Kaune T, Rosendahl J, Nagasaki M, Uezono Y, Algül H, Nakayama K, Matsubara Y, Aoki Y, Férec C, Mori Y, Witt H, Shimosegawa T: Variants That Affect Function of Calcium Channel TRPV6 Are Associated With Early-onset Chronic Pancreatitis. Gastroenterology 158: 1626-1641, 2020.
33. Schwarz Y, Oleinikov K, Schindeldecker B, Wyatt A, Weißgerber P, Flockerzi V, Boehm U, Freichel M, Bruns D: TRPC channels regulate Ca2+-signaling and short-term plasticity of fast glutamatergic synapses. PLoS Biol. 17, e3000445, 2019.
34. Blum T, Moreno-Pérez A, Pyrski M, Bufe B, Arifovic A, Weissgerber P, Freichel M, Zufall F, Leinders-Zufall T: Trpc5 deficiency causes hypoprolactinemia and altered function of oscillatory dopamine neurons in the arcuate nucleus. Proc Natl Acad Sci 116, 15236-15243, 2019.
35. Bacmeister L, Segin S, Medert R, Lindner D, Freichel M, Camacho Londoño JE: Assessment of PEEP-Ventilation and the Time Point of Parallel-Conductance Determination for Pressure-Volume Analysis Under β-Adrenergic Stimulation in Mice. Front Cardiovasc Med 6: 36, 2019.
36. Egorov AV, Schumacher D, Medert R, Birnbaumer L, Freichel M, Draguhn A. TRPC channels are not required for graded persistent activity in entorhinal cortex neurons. Hippocampus 29: 1038-1048, 2019.
37. Tiapko O, Shrestha N, Lindinger S, Guedes de la Cruz G, Graziani A, Klec C, Butorac C, Graier WF, Kubista H, Freichel M, Birnbaumer L, Romanin C, Glasnov T, Groschner K: Lipid-independent control of endothelial and neuronal TRPC3 channels by light. Chem Sci 10, 2837-2842, 2019.
38. Fecher-Trost C, Lux F, Busch KM, Raza A, Winter M, Hielscher F, Belkacemi T, van der Eerden B, Boehm U, Freichel M, Weissgerber P: Maternal Transient Receptor Potential Vanilloid 6 (Trpv6) Is Involved In Offspring Bone Development. J Bone Miner Res 34, 699-710, 2019.
39. Huber M, Cato ACB, Ainooson GK, Freichel M, Tsvilovskyy V, Jessberger R, Riedlinger E, Sommerhoff CP, Bischoff SC: Regulation of the pleiotropic effects of tissue-resident mast cells. J Allergy Clin Immunol 144: 531-545, 2019.
40. Sachdeva R, Fleming T, Schumacher D, Homberg S, Stilz K, Mohr F, Wagner AH, Tsvilovskyy V, Mathar I, Freichel M: Methylglyoxal evokes acute Ca2+ transients in distinct cell types and increases agonist-evoked Ca2+entry in endothelial cells via CRAC channels. Cell Calcium 78, 66-75, 2019.
41. Schumacher D, Morgenstern J, Oguchi Y, Volk N, Kopf S, Groener JB, Nawroth PP, Fleming T, Freichel M: Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes. Mol Metab 18, 143-152, 2018.
42. Cheung SY, Henrot M, Al-Saad M, Baumann M, Muller H, Unger A, Rubaiy HN, Mathar I, Dinkel K, Nussbaumer P, Klebl B, Freichel M, Rode B, Trainor S, Clapcote SJ, Christmann M, Waldmann H, Abbas SK, Beech DJ, Vasudev NS: TRPC4/TRPC5 channels mediate adverse reaction to the cancer cell cytotoxic agent (-)-Englerin A. Oncotarget 9, 29634-29643, 2018.
43. Tsvilovskyy V, Solis-Lopez A, Öhlenschläger K, Freichel M: Isolation of Peritoneum-derived Mast Cells and Their Functional Characterization with Ca2+-imaging and Degranulation Assays. J Vis Exp 137, 2018.
44. Tsvilovskyy V, Solís-López A, Schumacher D, Medert R, Roers A, Kriebs U, Freichel M: Deletion of Orai2 augments endogenous CRAC currents and degranulation in mast cells leading to enhanced anaphylaxis. Cell Calcium 71, 24-33, 2018.
45. Sachdeva R, Schlotterer A, Schumacher D, Matka C, Mathar I, Dietrich N, Medert R, Kriebs U, Lin J, Nawroth P, Birnbaumer L, Fleming T, Hammes HP, Freichel M: TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation. Mol Metab 9, 156-167, 2018.
46. Dutta Banik D, Martin LE, Freichel M, Torregrossa AM, Medler KF:  TRPM4 and TRPM5 are both required for normal signaling in taste receptor cells. Proc Natl Acad Sci USA 115, E772-E781, 2018.
47. Lehmann LH, Jebessa ZH, Kreusser MM, Horsch A, He T, Kronlage M, Dewenter M, Sramek V, Oehl U, Krebs-Haupenthal J, von der Lieth AH, Schmidt A, Sun Q, Ritterhoff J, Finke D, Völkers M, Jungmann A, Sauer SW, Thiel C, Nickel A, Kohlhaas M, Schäfer M, Sticht C, Maack C, Gretz N, Wagner M, El-Armouche A, Maier LS, Londoño JEC, Meder B, Freichel M, Gröne HJ, Most P, Müller OJ, Herzig S, Furlong EEM, Katus HA, Backs J: A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway. Nat Med 24, 62-72, 2018.
48. Bröker-Lai J, Kollewe A, Schindeldecker B, Pohle J, Nguyen Chi V, Mathar I, Guzman R, Schwarz Y, Lai A, Weißgerber P, Schwegler H, Dietrich A, Both M, Sprengel R, Draguhn A, Köhr G, Fakler B, Flockerzi V, Bruns D, Freichel M: Heteromeric channels formed by TRPC1, TRPC4 and TRPC5 define hippocampal synaptic transmission and working memory. EMBO J 36, 2770-89, 2017.
49. Hartmann AK, Arande Lopez P, Zajac M, Freichel M, Schild R, Radsak MP, Stassen M: 9-phenanthrol enhances the generation of an CD8± T cell response following transcutaneous immunization with imiquimod in mice. J Dermatol Sci 87, 260-7, 2017.
50. Beck A, Götz V, Qiao S, Weissgerber P, Flockerzi V, Freichel M, Boehm U: Functional characterization of transient receptor potential (TRP) channel C5 in female murine gonadotropes. Endocrinology 158, 887-902, 2017.
51. Morgenstern J, Fleming T, Schumacher D, Eckstein V, Freichel M, Herzig S, Nawroth P: Loss of glyoxalase 1 induces compensatory mechanism to achieve dicarbonyl detoxification in mammalian Schwann cells. J Biol Chem 292, 3224-38, 2017.
52. Solís-López A, Kriebs U, Marx A, Mannebach S, Liedtke WB, Caterina MJ, Freichel M, Tsvilovskyy VV: Analysis of TRPV channel activation by stimulation of FCεRI and MRGPRn receptors in mouse peritoneal mast cells. PLoS One 12: e0171366, 2017.
53. Danielczok J, Hertz L, Ruppenthal S, Kaiser E, Petkova-Kirova P, Bogdanova A, Krause E, Lipp P, Freichel M, Kaestner L, Birnbaumer L: Does erythropoietin regulate TRPC channels in red blood cells? Cell Physiol Biochem 41: 1219-228, 2017.
54. Rixecker T, Mathar I, Medert R, Mannebach S, Pfeifer A, Lipp P, Tsvilovskyy V, Freichel M: TRPM4-mediated control of FcεRI-evoked Ca(2+) elevation comprises enhanced plasmalemmal trafficking of TRPM4 channels in connective tissue type mast cells. Sci Rep 6: 32981, doi: 10.1038/srep32981, 2016.
55. Kurland DB, Gerzanich V, Karimy JK, Woo SK, Vennekens R, Freichel M, Nilius B, Bryan J, Simard JM: The Sur1-Trpm4 channel regulates NOS2 transcription in TLR4-activated microglia. J Neuroinflammation 13: 130, 2016.
56. Menigoz A, Ahmed T, Sabanov V, Philippaert K, Pinto S, Kerselaers S, Segal A, Freichel M, Voets T, Nilius B, Vennekens R, Balschun D. TRPM4-dependent post-synaptic depolarization is essential for the induction of NMDA receptor-dependent LTP in CA1 hippocampal neurons. Pflugers Arch 468: 593-607, 2016.
57. Klepac K, Kilic A, Gnad T, Brown LM, Herrmann B, Wilderman A, Balkow A, Glöde A, Simon K, Lidell ME, Betz MJ, Enerbäck S, Wess J, Freichel M, Blüher M, König G, Kostenis E, Insel PA, Pfeifer A. The Gq signalling pathway inhibits brown and beige adipose tissue. Nat Commun 7: 10895, 2016.
58. Zhang W, Freichel M, van der Hoeven F, Nawroth PP, Katus H, Kälble F, Zitron E, Schwenger V. Novel endothelial cell-specific AQP1 knockout mice confirm the crucial role of endothelial AQP1 in ultrafiltration during peritoneal dialysis. PLos One 11:e0135513, doi: 10.1371/journal.pone.0145513, 2016.
59. Jha A, Singh AK, Weissgerber P, Freichel M, Flockerzi V, Flavell RA, Jha MK: Essential roles for Cavβ2 and Cav1 channels in thymocyte development and T cell homeostasis. Sci Signal 8: ra103., 2016.
60. Uhl S, Freichel M, Mathar I: Contractility measurements on isolated papillary muscles for the investigation of cardiac inotropy in mice. J Vis Exp 103: 53076, 2015.
61. Camacho Londoño JE, Tian Q, Hammer K, Schröder L, Camacho Londoño J, Reil JC, He T, Oberhofer M, Mannebach S, Mathar I, Philipp SE, Tabellion W, Schweda F, Dietrich A, Kaestner L, Laufs U, Birnbaumer L, Flockerzi V, Freichel M*, Lipp P*: A background Ca2+ entry pathway mediated by TRPC1/TRPC4 is critical for development of pathological cardiac remodelling. Eur Heart J 36: 2257-2266, 2015 *shared senior authorship
62. Kecskés M, Jacobs G, Kerselaers S, Syam N, Menigoz A, Vangheluve P, Freichel M, Flockerzi V, Voets T, Vennekens R: The (Ca2+)-activated cation channel TRPM4 is a negative regulator of angiotensin II-induced cardiac hypertrophy. Basic Res Cardiol 110: 501, 2015.
63. Uhl S, Mathar I, Vennekens R, Freichel M: Adenylyl cyclase-mediated effects contribute to increased Isoprenaline-induced cardiac contractility in TRPM4-deficient mice. J Mol Cell Cadiol 74: 307-17, 2014.
64. Kang D, Wang J, Hogan JO, Vennekens R, Freichel M, White C, Kim D: Increase in cytosolic Ca²⁺ produced by hypoxia and other depolarizing stimuli activates a non-selective cation channel in chemoreceptor cells of rat carotid body. J Physiol 592: 1975-92, 2014.
65. Mathar I, Kecskes M, Van der Mieren G, Jacobs G, Camacho Londoño JE, Uhl S, Flockerzi V, Voets T, Freichel M, Nilius B, Herijgers P, Vennekens R: Increased β-adrenergic inotropy in ventricular myocardium from Trpm4^-/- mice. Circ Res 114: 283-94, 2014.
66. Tian J, Thakur DP, Lu Y, Zhu Y, Freichel M, Flockerzi V, Zhu MX: Dual depolarization responses generated within the same lateral septal neurons by TRPC4-containing channels. Pflugers Arch 466: 1301-16, 2014.
67. Boudes M, Uvin P, Pinto S, Freichel M, Birnbaumer L, Voets T, De Ridder D, Vennekens R: Crucial role of TRPC1 and TRPC4 in cystitis-induced neuronal sprouting and bladder overactivity. PLoS One 8: e69550, 2013.
68. Loga F, Domes K, Freichel M, Flockerzi V, Dietrich A, Birnbaumer L, Hofmann F, Wegener JW. The role of cGMP/cGKI signalling and Trpc channels in regulation of vascular tone. Cardiovasc Res 100: 280-7, 2013.
69. Harper MT, Londoño JE, Quick K, Londoño JC, Flockerzi V, Philipp SE, Birnbaumer L, Freichel M, Poole AW: Transient receptor potential channels function as a coincidence signal detector mediating phosphatidylserine exposure. Sci Signal 6: ra50, 2013.
70. Matti U, Pattu V, Halimani M, Schirra C, Krause E, Liu Y, Weins L, Chang HF, Guzman R, Olausson J, Freichel M, Schmitz F, Pasche M, Becherer U, Bruns D, Rettig J: Synaptobrevin2 is the v-SNARE required for cytotoxic T-lymphocyte lytic granule fusion. Nat Commun 4: 1439, 2013.
71. Phelan KD, Shwe UT, Abramowitz J, Wu H, Rhee SW, Howell MD, Gottschall PE, Freichel M, Flockerzi V, Birnbaumer L, Zheng F: Canonical transient receptor channel 5 (TRPC5) and TRPC1/4 contribute to seizure and excitotoxicity by distinct cellular mechanisms. Mol Pharmacol 83: 429-38, 2013.
72. Suresh Babu S, Wojtowicz A, Freichel M, Birnbaumer L, Hecker M, Cattaruzza M: Mechanisms of stretch-induced activation of the mechanotransducer zyxin in vascular cells. Sci Signal 5: ra91, 2012.
73. Schattling B, Steinbach K, Thies E, Kruse M, Menigoz A, Ufer F, Flockerzi V, Brück W, Pongs O, Vennekens R, Kneussel M, Freichel M, Merkler D, Friese MA: TRPM4 cation channel mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med 18: 1805-11, 2012.
74. Woudenberg-Vrenken TE, Lameris AL, Weißgerber P, Olausson J, Flockerzi V, Bindels RJ, Freichel M, Hoenderop JG: Functional TRPV6 channels are crucial for transepithelial Ca²⁺ absorption. Am J Physiol Gastrointest Liver Physiol 303: G879-85, 2012.
75. Quick K, Zhao J, Eijkelkamp N, Linley JE, Rugiero F, Cox JJ, Raouf R, Gringhuis M, Sexton JE, Abramowitz J, Taylor R, Forge A, Ashmore J, Kirkwood N, Kros CJ, Richardson GP, Freichel M, Flockerzi V, Birnbaumer L, Wood JN: TRPC3 and TRPC6 are essential for normal mechanotransduction in subsets of sensory neurons and cochlear hair cells. Open Biol 2: 120068, 2012.
76. Stroh O, Freichel M, Kretz O, Birnbaumer L, Hartmann J, Egger V: NDMDA receptor-dependent synaptic activation of TRPC channels in olfactory bulb granule cells. J Neurocsi 32, 5737-46, 2012.
77. Weissgerber P, Kriebs U, Tsvilovskyy V, Olausson J, Kretz O, Stoerger C, Mannebach S, Wissenbach U, Vennekens R, Middendorff R, Flockerzi V, Freichel M: Excision of Trpv6 gene leads to severe defects in epididymal Ca²⁺ absorption and male fertility much like single D541A pore mutation. J Biol Chem 287: 17930-41, 2012.
78. Weissmann N, Sydykov A, Kalwa H, Storch U, Fuchs B, Mederos y Schnitzler M, Brandes RP, Grimminger F, Meissner M, Freichel M, Offermanns S, Veit F, Pak O, Krause KH, Schermuly RT, Brewer AC, Schmidt HH, Seeger W, Shah AM, Gudermann T, Ghofrani HA, Dietrich A: Activation of TRPC6 channels is essential for lung ischaemia-reperfusion induced oedema in mice. Nat Commun 3, 649, 2012.
79. Samapati R, Yang Y, Yin J, Stoerger C, Arenz C, Dietrich A, Gudermann T, Adam D, Wu S, Freichel M, Flockerzi V, Uhlig S, Kuebler WM: Lund endothelial Ca²⁺ and permeability response to platelet-activating factor is mediated by acid sphingomyelinase and transient receptor potential classical 6. Am J Respir Crit Care Med 185: 160-70, 2012.
80. Sudivakkam PC, Freichel M, Singh V, Yuan JP, Vogel SM, Flockerzi V, Malik AB, Tiruppathi C: The Ca²⁺ sensor STIM1 is necessary and sufficient for the store-operated Ca²⁺ entry function of TRPCs in endothelial cells. Mol Pharmacol 8: 510-26, 2012.
81. Phelan KD, Mock MM, Kretz O, Shwe UT, Kozhemyakin M, Greenfield LJ, Dietrich A, Birnbaumer L, Freichel M, Flockerzi V, Zheng F: Heteromeric TRPC1/TRPC4 channels play a critical role in epileptiform burst firing and seizure-induced neurodegeneration. Mol Pharmacol 81: 384-92, 2012.
82. van der Eerden BC, Weissgerber P, Fratzl-Zelman N, Olausson J, Hoenderop JG, Schreuders-Koedam M, Eijken M, Roschger P, de Vries TJ, Chiba H, Klaushofer K, Flockerzi V, Bindels RJ, Freichel M, van Leeuwen JP: The transient receptor potential channel TRPV6 is dynamically expressed in bone cells but is not crucial for bone mineralization in mice. J Cell Physiol 227: 1951-9, 2012.
83. Xue T, Do MT, Riccio A, Jiang Z, Hsieh J, Wang HC, Merbs SL, Welsbie DS, Yoshioka T, Weissgerber P, Stolz S, Flockerzi V, Freichel M, Simon MI, Clapham DE, Yau KW: Melanopsin signalling in mammalian iris and retina. Nature 479: 67-73, 2011.
84. Klaiber M, Dankworth B, Kruse M, Hartmann M, Nikolaev VO, Yang RB, Völker K, Gassner B, Oberwinkler H, Feil R, Freichel M, Groschner K, Skryabin BV, Frantz S, Birnbaumer L, Pongs O, Kuhn M: A cardiac pathway of cyclic GMP-independent signaling of guanylyl cyclase A, the receptor for atrial natriuretic peptide. Proc Natl Acad Sci U S A 108: 18500-5, 2011.
85. Weissgerber P, Kriebs U, Tsvilovskyy V, Olausson J, Kretz O, Stoerger C, Vennekens R, Wissenbach U, Middendorff R, Flockerzi V, Freichel M: Male fertility depends on Ca²⁺ absorption by TRPV6 in epididymal epithelia. Sci Signal 4: ra27, 2011.
86. Custodis F, Gertz K, Balkaya M, Prinz V, Mathar I, Stamm C, Kronenberg G, Kazakov A, Freichel M, Böhm M, Endres M, Laufs U: Heart rate contributes to the vascular effects of chronic mental stress: effects on endothelial function and ischemic brain injury in mice. Stroke 42: 1742-9, 2011.
87. Meissner M, Weissgerber P, Londoño JE, Prenen J, Link S, Ruppenthal S, Molkentin JD, Lipp P, Nilius B, Freichel M, Flockerzi V: Moderate calcium channel dysfunction in adult mice with inducible cardiomyocyte-specific excision of the cacnb2 gene. J Biol Chem 286: 15857-82, 2011.
88. Mathar I, Vennekens R, Meissner M, Kees F, VAn der Mieren G, Camacho-Londoño, JE, Uhl S, Voets T, Hummel B, Herijgers P, Nilius B, Flockerzi V, Schweda F, Freichel M: Increased catecholamine secretion contributes to hypertension in TRPM4-deficient mice. J Clin Invest 120: 3267-79, 2010.
89. Klaiber M, Kruse M, Völker K, Schröter J, Feil R, Freichel M, Gerling A, Feil S, Dietrich A, Londoño, JE, Baba HA, Abramowitz J, Birnbaumer L, Penninger JM, Pongs O, Kihn M: Novel insights into the mechanisms mediating the local antihypertrophic effects of cardiac atrial natriuretic peptide: role of cGMP-dependent protein kinase and RGS2. Basic Res Cardiol 105: 583-95, 2010.
90. Jha MK, Badou A, Meissner M, McRory JE, Freichel M, Flockerzi V, Flavell RA: Defective survival of naïve CD8⁺ T lymphocytes in the absence of β3 regulatory subunit of CaV channels. Nat Immunol 10: 1275-82, 2009.
91. Link S, Meissner M, Held B, Beck A, Weißgerber P, Freichel M, Flockerzi V: Diversity and developmental expression of CaVb2 proteins in the murine heart and their influence on calcium current in murine heart. J Biol Chem 284: 30129-37, 2009.
92. Kuhn S, Knirsch M, Rüttinger L, Kasperek S, Winter H, Freichel M, Flockerzi V, Knipper M, Engel J: Ba²⁺ currents in inner and outer hair cells of mice lacking the voltage-dependent Ca²⁺ channel subunits β3 or β4. Channels (Austin) 3: 366-76, 2009.
93. Tsvilovskyy VV, Zholos AV, Aberle T, Philipp SE, Dietrich A, Zhu MX, Birnbaumer L, Freichel M, Flockerzi V: Deletion of TRPC4 and TRPC6 impairs smooth muscle contraction and intestinal motility in vivo. Gastroenterology 137: 1415-24, 2009.
94. Gerzanich V, Woo K, Vennekens R, Tsymbalyuk SO, Ivanova S, Ivanov A, Geng Z, Chen Z, Flockerzi V, Nilius B, Freichel M, Simard JM: De novo expression of TRPM4 initiates secondary hemorrhage in spinal cord injury. Nat Med 15: 185-91, 2009.
95. Bair AM, Thippegowda PB, Freichel M, Cheng N, Ye RD, Vogel SM, Yu Y, Flockerzi V, Malik AB, Tiruppathi C: Ca²⁺ entry via TRPC channels is necessary for thrombin-induced NF-κB activation in endothelial cells through AMP-activated protein kinase and protein kinase Cδ. J Biol Chem 284: 563-74, 2009.
96. Shimizu T, Owsianik G, Freichel M, Flockerzi V, Nilius B, Vennekens R: TRPM4 regulates migration of mast cells in mice. Cell Calcium 45: 226-32, 2009.
97. Hartmann J, Dragicevic E, Adelsberger H, Henning H, Sumsser M, Abramowitz J, Blum R, Dietrich M, Freichel M, Flockerzi V, Birnbaumer L, Konnerth A: TRPC3 channels are required for synaptic transmission and motor coordination. Neuron 59: 392-8, 2008.
98. Otsuguro K, Tang J, Tang Y, Xiao R, Freichel M, Tsvilovskyy VV, Ito S, Flockerzi V, Zhu MX, Zholos AV: Isoform-specific inhibition of TRPC4 channel by phosphatidylinositol 4,5-bisphosphate. J Biol Chem 238: 10026-36, 2008.
99. Vennekens R, Olausson J, Meissner M, Bloch W, Mathar I, Philipp SE, Schmitz F, Weissgerber P, Nilius B, Flockerzi V, Freichel M: Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel TRPM4. Nat Immunol 8: 312-20, 2007.
100. Andronache Z, Ursu D, Lehnert S, Freichel M, Flockerzi V, Melzer W: The auxiliary subunit γ1 of the skeletal muscle L-type calcium channel is an endogenous calcium antagonist. Proc Natl Acad Sci U S A 104: 17885-90, 2007.
101. Held B, Tsvilovskyy V, Meissner M, Kästner L, Ludwig A, Mossmang S, Lipp P, Freichel M, Flockerzi V: Ca²⁺ channel currents and contraction in CaVβ3-deficient ileum smooth muscle from mouse. Cell Calcium 42: 477-87, 2007.
102. Gross SA, Wissenbach U, Philipp SE, Freichel M, Cavalié A, Flockerzi V: Murine ORAI2 splice variants form functional CRAC channels. J Biol Chem 282: 19375-84, 2007.
103. Singh U, Sun T, Looman C, Heuchel R, Elliot R, Freichel M, Meissner M, Flockerzi V, Fundele R: Expression and function of the gene encoding the voltage-dependent calcium channel beta3-subunit in the mouse placenta. Placenta 28: 412-20, 2007.
104. Badou A, Jha MK, Matza D, Mehal WZ, Freichel M, Flockerzi V, Flavell RA: Critical role for the beta regulatory subunits of Cav channels in T lymphocyte funtion. Proc Natl Acad Sci USA 103: 15529-34, 2006.
105. Weißgerber P, Held B, Bloch W, Kästner L, Chien K, Fleischmann B, Lipp P, Flockerzi V, Freichel M: Reduced cardiac L-type Ca²⁺ current in CaVβ2^-/- embryos impairs cardiac development and contraction with secondary defects in vascular maturation. Circ Res 99: 749-57, 2006.
106. Aneiros E, Philipp S, Lis A, Freichel M, Cavalié A: Modulation of Ca²⁺ signalling by Na⁺/Ca²⁺ exchangers in mast cells. J Immunol 174: 119-30, 2005.
107.   Berggren PO, Yang S, Murakami M, Efanov A, Uhles S, Köhler M, Moede T, Fernström A, Appelskog I, Aspinwall C, Zaitsev S, Larsson O, Moitosos de Vargas L, Fecher-Trost C, Weißgerber P, Ludwig A, Leibiger B, Juntti-Bergen L, Barker CJ, Gromada J, Freichel M, Leibiger I, Flockerzi V: Removal of Ca²⁺ channel β3 subunit enhances Ca²⁺ oscillations frequency and insulin exocytosis. Cell 119: 273-84, 2004.
108.   Ursu D, Schuhmeier RP, Freichel M, Flockerzi V, Melzer D: Altered Ca²⁺ current, Ca²⁺ release and force in adult mouse muscle fibers deficient of the DHP-receptor γ1 subunit. J Gen Physiol 124: 605-18, 2004.
109.   Munsch T, Freichel M, Flockerzi V, Pape H: Contribution of transient receptor potential channels to serotonin-mediated increase in GABA release from dendrites. Proc Natl Acad Sci USA 100: 16065-70, 2003.
110.   Nilius B, Prenen J, Droogmanns G, Voets T, Vennekens R, Freichel M, Wissenbach U, Flockerzi V: Voltage dependence of the Ca2+ activated cation channel TRPM4. J Biol Chem 278: 30813-20, 2003.
111.   Hirnet D*, Olausson J*, Fecher-Trost C, Bödding M, Nastainczyk W, Wissenbach U, Flockerzi V, Freichel M: The TRPV6 gene, cDNA and protein. Cell Calcium 33: 509-18, 2003.
112.   Bosel J, John M, Freichel M, Blind E: Signaling of the human calcium-sensing receptor expressed in HEK293-cells is modulated by protein kinases A and C. Exp Clin Endocrinol Diabetes 111: 21-6, 2003.
113.   Murakami M, Fleischmann B, De Felipe C, Freichel M, Trost C, Ludwig A, Wissenbach U, Schwegler H, Hofmann F, Hescheler J, Flockerzi V, Cavalié A: Pain perception in mice lacking the β3 subunit of voltage-activated calcium channels. J Biol Chem 277: 40342-51, 2002.
114.   Tiruppathi C, Freichel M, Vogel SM, Paria BC, Metha D, Flockerzi V, Malik AB: Impairment of store-operated Ca²⁺ entry in TRPC4^-/- mice interferes with thrombin-induced increase in lung microvascular permeability. Circ Res 91: 70-6, 2002.
115.   Held B, Freise D, Freichel M, Hoth M, Flockerzi V: Skeletal muscle L-type Ca²⁺ current modulation in γ1-deficient and wildtype myotubes by the γ1 subunit and cAMP. J Physiol 539: 459-68, 2002.
116.   Freichel M, Suh SH, Pfeifer A, Schweig U, Trost C, Weißgerber P, Biel M, Philipp S, Freise D, Droogmans G, Hofmann F, Flockerzi V, Nilius B: Lack of anendothelial store-operated Ca²⁺ current impairs agonist-dependent Ca²⁺ entry and vasorelaxation in TRP4 (CCE1)^-/- mice. Nat Cell Biol 3: 121-7, 2001.
117.   Wei L, Freichel M, Jaspers M, Cuppens H, Cassiman JJ, Droogmans G, Flockerzi V, Nilius B: Functional interaction between TRP4 and CFTR in mouse aorta endothelial cells. BMC Physiology 1: 3, 2001.
118.  Quitterer U, Hoffmann M, Freichel M, Lohse MJ: Paradoxical block of parathormone secretion is mediated by increased activity of G protein α subunits. J Biol Chem 276: 6763-9, 2001.
119.   Wissenbach U, Bödding M, Freichel M, Flockerzi V: Trp12, a novel Trp related protein from kidney. FEBS Lett 485: 127-34, 2000.
120.   Freise D, Held B, Wissenbach U, Pfeifer A, Trost C, Himmerkus N, Schweig U, Freichel M, Biel M, Hofmann F, Hoth M, Flockerzi V: Absence of the gamma subunit of the skeletal muscle dihydropyridine receptor increases L-type Ca²⁺ currents and alters channel inactivation properties. J Biol Chem 275: 14476-81, 2000.
121.   Zimmer S, Trost C, Wissenbach U, Philipp S, Freichel M, Flockerzi V, Cavalié A: Modulation of recombinant transient-receptor-potential-like (TRPL) channels by cytosolic Ca²⁺. Pflügers Arch 440: 409-17, 2000.
122.   Suh SH, Vennekens R, Manolopoulos VG, Freichel M, Schweig U, Prenen J, Flockerzi V, Droogmans G, Nilius B: Characterisation of explanted endothelial cells from mouse aorta: electrophysiology and Ca²⁺ signaling. Pflügers Arch 438: 612-20, 1999.
123.   Philipp S, Hambrecht J, Brqaslavski L, Schroth G, Freichel M, Murakami M, Cavalié A, Flockerzi V: A novel capacitative calcium entry channel expressed in excitable cells. EMBO J 17: 4274-82, 1998.
124.   Freichel M, Wissenbach U, Philipp S, Flockerzi V: Alternative splicing and tissue specific expression of the 5' truncated bCCE1 variant bCCE1Δ514. FEBS Lett 422: 354-8, 1998.
125.   Philipp S, Cavalié A, Freichel M, Wissenbach U, Zimmer S, Trost C, Marquart A, Manabu M, Flockerzi V: A mammalian capacitative calcium entry channel homologous to Drosophila TRP and TRPL. EMBO J 15: 6166-71, 1996.
126.   Freichel M, Zink-Lorenz A, Holloschi A, Hafner M, Flockerzi V, Raue F: Expression of a calcium-sensing receptor in a human medullary thyroid carcinoma cell line and its contribution to calcitonin secretion. Endocrinology 137: 3842-8, 1996.
127.   Biel M, Altenhofen W, Hullin R, Ludwig J, Freichel M, Flockerzi V, Dascal N, Kaupp UB, Hofmann F: Primary structure and functional expression of a cyclic nucleotide gated channel from rabbit aorta. FEBS Lett 329: 134-8, 1993.
128.   Hullin R, Singer-Lahat D, Freichel M, Biel M, Dascal N, Hofmann F, Flockerzi V: Calcium channel β subunit heterogeneity: functional expression of cloned cDNA from heart, aorta and brain. EMBO J 11: 885-90, 1992.

Reviews, book chapters and online courses:

1. Brings S, Fleming T, Freichel M, Muckenthaler MU, Herzig S, Nawroth PP: Dicarbonyls and advanced glycation end-products in the development of diabetic complications and targets for intervention. Int J Mol Sci 18: pii: E984, 2017.
2. Freichel M, Berlin M, Schürger A, Mathar I, Bacmeister L, Medert R, Frede W, Marx A, Segin S, Londoño JEC. TRP channels in the heart. In: Emir TLR, ed. Neurobiology of TRP channels. 2nd ed, Boca Raton (FL): CRC Press/Taylor & Francis, Chapter 9, PMID: 29356479, 2017.
3. Mathar I, Jacobs G, Kecskés M, Menigoz A, Phillipaert K, Vennekens R: Mammalian transient receptor potential (TRP) cation channels. Handb Exp Pharmacol 222: 462-481, 2014.
4. Freichel M, Tsvilovskyy V, Camacho Londoño JE: TRPC4- and TRPC4-containing channels. Handb Exp Pharmacol 222: 85-128, 2014.
5. Freichel M: TRP channels with diverse permeability profiles: regulation of blood pressure and fertility. In: Simpson, A. (ed.): Calcium signaling I: Regulation, mechanisms, effectors, role in disease and recent advances. The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com/?t=BL0293598-Freichel), 2014.
6. Freichel M, Almering J, Tsvilovskyy V: The role of TRP proteins in mast cells. Front Immunol 3: 150, 2012.
7. Freichel M, Kriebs U, Vogt D, Mannebach S, Weißgerber P: Strategies and protocols to generate mouse models with targeted mutations to analyze TRP channel functions. In: Zhu MX (ed.). TRP channels. CRC Press, Boca Raton (FL), chapter 8, 2011.
8. Freichel M, Flockerzi V: Biological functions of TRPs unravelled by spotaneous mutations and transgenic animals. Biochem Soc Trans 35: 120-3, 2007.
9. Freichel M, Vennekens R, Olausson J, Stolz S, Philipp S, Weißgerber P: Flockerzi V. Functional role of TRPC proteins in native systems: implications from knockout and knock-down studies. J Physiol 567: 59-66, 2005.
10. Flockerzi V, Jung C, Aberle T, Meissner M, Freichel M, Philipp SE, Nastainczyk W, Maurer P, Zimmermann R: Specific detection and semi-quantative analysis of TRPC4 protein expression by antibodies. Pflugers Arch 451: 81-6, 2005.
11. Freichel M, Vennekens R, Olausson J, Hoffmann M, Müller C, Stolz S, Scheunemann J, Weißgerber P, Flockerzi V: Functional role of TRPC proteins in vivo: lessons from TRPC-deficient mouse models. Biochem Biophys Res Commun 322: 1352-8, 2004.
12. Freichel M, Philipp P, Cavalié A, Flockerzi V: TRPC4 and TRPC4 deficient mice. Novartis Found Symp 258: 189-99; discussion 199-203, 263-6, 2004.
13. Freichel M, Schweig U, Stauffenberger S, Freise D, Schorb W, Flockerzi V: Store operated cation channels (SOCs) in the heart and cells of the cardiovascular system. Cell Physiol Biochem 9: 270-83, 1999.
14. Freise D, Himmerkus N, Schroth G, Trost C, Weißgerber P, Freichel M, Flockerzi V: Mutations of calcium channel β subunit genes in mice. Biol Chem 380: 897-902, 1999.

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