Christian Grimm, Prof. Dr. Dr.

Publications

Key publications

- Plesch E, Chen C-C, Butz E, Scotto Rosato A, Krogsaeter EK, Hua Y, Bartel K, Robaa D, Keller M, Teupser D, Holdt LM, Vollmar AM, Sippl W, Puertollano R, Medina DL, Biel M, Wahl-Schott C, Bracher F, Grimm C#: Isoform-selective agonist of TRPML2 reveals direct role in cytokine release from innate immune cells. eLIFE. pii: e39720, 2018.

Impact factor: 7.6

- Chao Y-K, Schludi V, Chen C-C, Butz E, Nguyen, P., Müller, M., Krüger J, Kammerbauer C, Vollmar, A., Berking C, Biel M, Wahl-Schott C, Grimm C#: TPC2 polymorphisms associated with a human hair pigmentation phenotype result in gain of channel function by independent mechanisms. PNAS 114:E8595-E8602, 2017.

Impact factor: 9.7

- Chen C-C, Butz E, Chao Y-K, Grishchuk Y, Becker L, Heller S, Slaugenhaupt S, Biel M, Wahl-Schott C, Grimm C#: Small molecules for early endosome specific patch-clamping. Cell Chem Biol 24:907-916, 2017.

Impact factor: 6.7

- Chen C-C, Chunlei C, Fenske S, Butz E, Chao Y-K, Biel M, Ren D, Wahl-Schott C, Grimm C#: Patch clamp technique to characterize ion channels in individual intact endolysosomes. Nature Protoc 12:1639-1658, 2017.

Impact factor: 12.4

- Nguyen P*, Grimm C*, Schneider L, Chao Y-K, Watermann A, Ulrich M, Mayr D, Wahl-Schott C, Biel M, Vollmar AM: Two-pore channel function is crucial for migration of invasive cancer cells. Cancer Res 77:1427-1438, 2017.

Impact factor: 9.1

- Ruas M, Davis LC, Chen C-C, Morgan AJ, Chuang K-T, Walseth TF, Grimm C, Garnham C, Powell T, Biel M, Wahl-Schott C, Parrington J, Galione A: Expression of Ca²⁺-permeable two-pore channels rescues NAADP signalling in TPC-deficient cells. EMBO J 34:1743-1758, 2015.

Impact factor: 10.6

- Sakurai Y, Kolokoltsov AA, Chen C-C, Tidwell MW, Bauta WE, Klugbauer N, Grimm C, Wahl-Schott C, Biel M, Davey RA: Two pore channels control Ebolavirus host cell entry and are drug targets for disease treatment, Science 347:995-998, 2015.

Impact factor: 33.6

- Chen C-C, Keller M, Hess M, Schiffmann R, Urban N, Wolfgardt A, Schaefer M, Bracher F, Biel M, Wahl-Schott C, Grimm C#: A small molecule restores function to TRPML1 mutant isoforms responsible for mucolipidosis type IV. Nature Commun 5:4681, 2014.

Impact factor: 12.4

- Grimm C, Holdt LM, Chen C-C, Hassan S, Müller C, Jörs S, Cuny H, Kissing S, Schröder B, Butz E, Northoff B, Castonguay J, Luber CA, Moser M, Spahn S, Lüllmann-Rauch R, Fendel C, Klugbauer N, Griesbeck O, Haas A, Mann M, Bracher F, Teupser D, Saftig P, Biel M, Wahl-Schott C: High susceptibility to fatty liver disease in two-pore channel 2-deficient mice. Nature Commun 5:4699, 2014.

Impact factor: 12.4

- Aneiros E, Cao L, Papakosta M, Stevens EB, Phillips SC, Grimm C#: Biophysical and molecular basis of TRPV1 proton gating. EMBO J 30:994-1002, 2011.

Impact factor: 10.6

- Grimm C, Jörs S, Saldanha SA, Obukhov AG, Pan B, Oshima K, Cuajungco MP, Chase P, Hodder P, Heller S: Small molecule activators of TRPML3. Cell Chem Biol (former Chem. & Biol.) 17:135-148, 2010.

Impact factor: 6.7

- Grimm C, Cuajungco MP, van Aken AFJ, Schnee M, Jörs S, Kros CJ, Ricci AJ, Heller S: A helix-breaking mutation in TRPML3 leads to constitutive activity underlying deafness in the varitint-waddler mouse. PNAS 104:19583-19588, 2007.

Impact factor: 9.7

* authors contributed equally; # corresponding or shared corresponding author

Full list of publications                                                         Link zu PubMed

Peer-reviewed scientific articles

37. Scotto-Rosato, A., Montefusco, S., Soldati, C., Di Paola, S., Monfregola, J., Polishchuk, E., Amabile, A., Grimm, C., Lombardo, A., De Matteis, M.A., Ballabio, A., Medina, D.L. (2019) TRPML1 links lysosomal calcium to autophagosome biogenesis through the activation of the
CaMKKβ/VPS34 pathway. Nature Commun., 10:5630, 2019.

36. Goodridge, J., Jacobs, B., Saetersmoen, M., Clement, D., Clancy, T., Skarpen, E., Brech, A., Landskron, J., Grimm, C., Pfefferle, A., Meza-Zepeda, L., Lorenz, S., Thune Wiiger, M., Louch, W.E., Heggernes Ask, F., Liu, L.L., Yi Sheng Oei, V., Kjällquist, U., Linnarsson, S., Patel, S., Taskén, K., Stenmark, H., Malmberg, K.-J. (2019) TRPML1-mediated modulation of dense-core granules determines functional potential in NK cells. Nature Commun., 10:514

35. Villella, V.R., Venerando, A., Cozza, G., Esposito, S., Ferrari, E., Monzani, R., Spinella, M.C., Oikonomou, V., Renga, G., Tosco, A., Rossin, F., Guido, S., Bear, C.E., Silano, M., Garaci, E., Chao, Y.-K., Grimm, C., Luciani, A., Romani, L., Piacentini, M., Raia, V., Kroemer, G. & Maiuri, L. (2019) A pathogenic role for cystic fibrosis transmembrane conductance regulator in celiac disease. EMBO J., pii:
e100101

—34.Plesch, E., Chen, C.-C., Butz, E., Scotto Rosato A., Krogsaeter, E.K., Hua, Y., Bartel, K., Robaa, D., Keller, M., Teupser, D., Holdt, L.M., Vollmar, A.M., Sippl, W., Puertollano, R., Medina, D.L., Biel, M., Wahl-Schott, C., Bracher, F., Grimm, C.# (2018) Selective agonist of TRPML2 reveals direct role in cytokine release from innate immune cells. eLIFE 7. pii: e39720

—33.Chao, Y.-K., Schludi, V., Chen, C.-C., Butz, E., Nguyen, P., Müller, M., Krüger J, Kammerbauer C., Vollmar, A., Berking, C., Biel, M., Wahl-Schott, C., Grimm, C.# (2017) TPC2 polymorphisms associated with a human hair pigmentation phenotype result in gain of channel function by independent mechanisms. PNAS 114:E8595-E8602

—32.Castonguay, J., Orth, J.H.C., Müller, T., Sleman, F., Grimm, C., Wahl-Schott, C., Biel, M., Mallmann, R.T., Bildl, W., Schulte, U., Klugbauer, N. (2017) The two-pore channel 1 is required for efficient protein processing in early and recycling endosomes. Sci. Rep. 7:10038

—31.Chen, C.-C., Butz, E., Chao, Y.-K., Grishchuk, Y., Becker, L., Heller, S., Slaugenhaupt, S., Biel, M., Wahl-Schott, C., Grimm, C.# (2017) Small molecules for early endosome specific patch-clamping. Cell Chem. Biol., 24:907-916

—30.Chen, C.-C., Chunlei, C., Fenske, S., Butz, E., Chao, Y.-K., Biel, M., Ren, D., Wahl-Schott, C., Grimm, C.# (2017) Patch clamp technique to characterize ion channels in individual intact endolysosomes. Nature Protoc., 12:1639-1658

—29.Bobak, N., Feliciangeli, S., Chen, C.-C., Soussia, I.B., Bittner, S., Biel, M., Wahl-Schott, C., Grimm, C., Meuth, S.G., Lesage, F. (2017) Recombinant tandem of pore-domains in a weakly inward rectifying K+ channel 2 (TWIK2) forms active lysosomal channels. Sci. Rep., 7:649

—28.Nguyen, P.*, Grimm, C.*, Schneider, L., Chao, Y.-K., Watermann, A., Ulrich, M., Mayr, D., Wahl-Schott, C., Biel, M., Vollmar, A.M. (2017) Two-pore channel function is crucial for migration of invasive cancer cells. Cancer Res., 77:1427-1438

—27.Kilpatrick, B.S., Yates, E., Grimm, C., Schapira, A.H., Patel, S. (2016) Endo-lysosomal TRP mucolipin-1 triggers global ER Ca2+ release and Ca2+ influx. J. Cell Sci., 129:3859-3867

—26.Beck, S., Henß, L., Weidner, T., Herrmann, J., Müller, R., Chao, Y.-K., Grimm, C., Weber, C., Sliva, K., Schnierle, B.S. (2016) Identification of entry inhibitors of Ebola virus pseudotyped vectors from a myxobacterial compound library. Antiviral Res. S0166-3542(16)30014-30016

—25.Müller, C., Binder, U., Maurer, E., Grimm, C., Giera, M., Bracher, F. (2015) Fungal sterol C22-desaturase is not an antimycotic target as shown by selective inhibitors and testing on clinical isolates. Steroids 101:1-6

—24.Ruas, M., Davis, L.C., Chen, C.-C., Morgan, A.J., Chuang, K.-T., Walseth, T.F., Grimm, C., Garnham, C., Powell, T., Biel, M., Wahl-Schott, C., Parrington, J., Galione, A. (2015) Expression of Ca²⁺-permeable two-pore channels rescues NAADP signalling in TPC-deficient cells. EMBO J., 34:1743-1758

—23.Sakurai, Y., Kolokoltsov, A.A., Chen, C.-C., Tidwell, M.W., Bauta, W.E., Klugbauer, N., Grimm, C., Wahl-Schott, C., Biel, M., Davey, R.A. (2015) Two pore channels control Ebolavirus host cell entry and are drug targets for disease treatment, Science, 347:995-998

—22.Grimm, C., Holdt, L.M., Chen, C.-C., Hassan, S., Müller, C., Jörs, S., Cuny, H., Kissing, S., Schröder, B., Butz, E., Northoff, B., Castonguay, J., Luber, C.A., Moser, M., Spahn, S., Lüllmann-Rauch, R., Fendel, C., Klugbauer, N., Griesbeck, O., Haas, A., Mann, M., Bracher, F., Teupser, D., Saftig, P., Biel, M., Wahl-Schott, C. (2014) High susceptibility to fatty liver disease in two-pore channel 2-deficient mice. Nature Commun., 5:4699. doi: 10.1038/ncomms5699

—21.Cuajungco, M.P., Basilio, L.C., Silva, J., Hart, T., Tringali, J., Chen, C.-C., Biel, M., Grimm, C.# (2014) Cellular zinc levels are modulated by TRPML1-TMEM163 interaction. Traffic, 15:1247-1265. doi: 10.1111/tra.12205

—20.Chen, C.-C.,Keller, M., Hess, M., Schiffmann, R., Urban, N., Wolfgardt, A., Schaefer, M., Bracher, F., Biel, M., Wahl-Schott, C., Grimm, C.# (2014) A small molecule restores function to TRPML1 mutant isoforms responsible for mucolipidosis type IV. Nature Commun., 5:4681. doi: 10.1038/ncomms5681

—19.Gao, Z., Grimm, C., Becker, L., Ricci, A.J., Heller, S. (2013) A novel ion channel formed by interaction of TRPML3 with TRPV5. PLoS ONE, 8:e58174

—18.Grimm, C.#, Jörs, S., Gao, Z., Obukhov, A.G., Heller, S. (2012) Constitutive activity of TRPML2 and TRPML3 channels versus activation by low extracellular sodium and small molecules. J. Biol. Chem., 287: 22701-22708

—17.Papakosta, M., Haythornthwaite, A., Cao, L., Stevens, E.B., Burgess, G., Russell, R., Cox, P., Phillips, S.C., Grimm, C.# (2011) The chimeric approach reveals that differences in the TRPV1 pore domain determine species-specific sensitivity to block of heat activation. J. Biol. Chem., 286:39663-39672

—16.Aneiros, E., Cao, L., Papakosta, M., Stevens, E.B., Phillips, S.C., Grimm, C.# (2011) Biophysical and molecular basis of TRPV1 proton gating. EMBO J., 30:994-1002

—15.Jörs, S.*, Grimm, C.*, Becker, L., Heller, S. (2010) Genetic inactivation of Trpml3 does not lead to hearing and vestibular impairment in mice. PLoS ONE, 5:e14317

—14.Lee, K.P.*, Nair, A.*, Grimm, C.*, van Zeeland, F., Heller, S., Bindels, R.J.M., Hoenderop, G.J. (2010) A helix-breaking mutation in the epithelial Ca2+ channel TRPV5 leads to reduced Ca2+ dependent inactivation. Cell Calcium, 48:275-287

—13.Hoffmann, A.*, Grimm, C.*, Kraft, R., Goldbaum, O., Wrede, A., Nolte, C., Hanisch, U.K., Richter-Landsberg, C., Brück, W., Kettenmann, H., Harteneck, C. (2010) TRPM3 is expressed in sphingosine-responsive myelinating oligodendrocytes. J. Neurochem., 114:654-665

—12.Grimm, C.*, Jörs, S.*, Saldanha, S.A.*, Obukhov, A.G., Pan, B., Oshima, K., Cuajungco, M.P., Chase, P., Hodder, P., Heller, S. (2010) Small molecule activators of TRPML3. Cell Chem. Biol., 17:135-148

—11.Samie, M.A., Grimm, C., Evans, J.A., Curcio-Morelli, C., Heller, S., Slaugenhaupt, S.A., Cuajungco, M.P. (2009) The tissue-specific expression of TRPML2 (Mcoln-2) gene is influenced by the presence of TRPML1. Eur. J. Physiol., 459:79-91

—Grimm, C.*, Jörs, S.*, Heller, S. (2009) Life and death of sensory hair cells expressing constitutively active TRPML3. J. Biol. Chem., 284:13823-13831

—10.D’hoedt, D., Owsianik, G., Prenen, J., Cuajungco, M.P., Grimm, C., Heller, S., Voets, T., Nilius, B. (2008) Stimulus-specific modulation of the cation channel TRPV4 by PACSIN 3. J. Biol. Chem., 283:6272-6280

—9.Grimm, C., Cuajungco, M.P., van Aken, A.F.J., Schnee, M., Jörs, S., Kros, C.J., Ricci, A.J., Heller, S. (2007) A helix-breaking mutation in TRPML3 leads to constitutive activity underlying deafness in the varitint-waddler mouse. PNAS, 104:19583-19588

—8.Senn, P., Oshima, K., Teo, D., Grimm, C., Heller, S. (2007) Robust postmortem survival of murine vestibular and cochlear stem cells. JARO, 8:194-204

—7.Oshima, K., Grimm, C., Corrales, E., Senn, P., Martinez Monedero, R., Géléoc, G.S.G., Edge, A., Holt, J.R., Heller, S. (2007) Differential distribution of stem cells in the auditory and vestibular organs of the inner ear. JARO, 8:18-31

—6.Cuajungco, M.P.*, Grimm, C.*, Oshima, K., D’hoedt, D., Nilius, B., Mensenkamp, A.R., Bindels, R.J.M., Plomann, M., Heller, S. (2006) PACSINS bind to the TRPV4 cation channel: PACSIN 3 modulates the subcellular localization of TRPV4. J. Biol. Chem., 281:18753-18762

—5.Kraft, R., Grimm, C., Frenzel, H., Harteneck, C. (2006) Inhibition of TRPM2 cation channels by N-(p-amylcinnamoyl)anthranilic acid. Br. J. Pharmacol., 148:264-273

—4.Grimm, C.*, Kraft, R.*, Schultz, G., Harteneck, C. (2005) Activation of the melastatin-related cation channel TRPM3 by D-erythro-sphingosine. Mol. Pharmacol., 67:798-805

—3.Xu, S.Z., Zeng, F., Boulay, G., Grimm, C., Harteneck, C., Beech, D.J. (2005) Block of TRPC5 channels by 2-aminoethoxydiphenyl borate: differential, extracellular and voltage-dependent effect. Br. J. Pharmacol., 145:405-414

—2.Kraft, R., Grimm, C., Grosse, K., Hoffmann, A., Sauerbruch, S., Kettenmann, H., Schultz, G., Harteneck, C. (2004) Hydrogen peroxide and ADP-ribose induce TRPM2-mediated calcium influx and cation currents in microglia. Am. J. Physiol. Cell Physiol., 286:C129-137

—1.Grimm, C.*, Kraft, R.*, Sauerbruch, S., Schultz, G., Harteneck, C. (2003) Molecular and functional characterization of the melastatin-related cation channel TRPM3. J. Biol. Chem., 278:21493-21501

* authors contributed equally; # corresponding or shared corresponding author

Reviews (Peer-reviewed)

—Krogsaeter, E.K., Biel, M., Wahl-Schott, C., Grimm, C. # (2018) The protein interaction networks of mucolipins and two-pore channels. BBA Mol. Cell Res., Accepted

—Grimm, C. #, Bartel, K., Vollmar, A.M., Biel, M. (2018) Endolysosomal Cation Channels and Cancer – a Link with Great Potential, Pharmaceuticals (Basel), 11(1).pii: E4

—Grimm, C., Butz, E., Chen, C.-C., Wahl-Schott, C., Biel, M. (2017) From mucolipidosis type IV to Ebola: TRPML and two-pore channels at the crossroads of endo-lysosomal trafficking and disease. Cell Calcium, 67:148-155

—Grimm, C.#, Chen, C.-C., Wahl-Schott, C., Biel, M. (2017) Two-pore channels: catalyzers of endolysosomal transport and function. Frontiers in Pharmacology, 8:45

—Grimm, C.# (2016) Endolysosomal cation channels as therapeutic targets - Pharmacology of TRPML channels. Messenger, 5:30–36

—Grimm, C.#, Hassan, S., Wahl-Schott, C., Biel, M. (2012) Role of TRPML and two-pore channels in endolysosomal cation homeostasis. J. Pharmacol. Exp. Ther. (Perspectives in Pharmacology), 342:236-244

—Grimm, C.#, de Groot, M., Aneiros, E. (2011) Dissecting TRPV1: lessons to be learned? CHANNELS, 5:201-204

—Cuajungco, M.P., Grimm, C., Heller, S. (2007) TRP channels as candidates for hearing and balance abnormalities in vertebrates. Biochem. Biophys. Acta, 1772:1022-1027

# corresponding or shared corresponding author

Book chapters

—Grimm, C.#, Barthmes, M., and Wahl-Schott, C. (2014) TRPML3, in: Nilius, B. and Flockerzi, V., Mammalian Transient Receptor Potential (TRP) cation channels, The Handbook of Experimental Pharmacology (HEP), Springer Publishing, 222:659-674

—Grimm, C.# and Cuajungco, M.P. (2014) Mucolipidosis type IV and TRPML channels, in: Koschak, A. and Weiss, N., Pathologies of Calcium Channels, Springer Publishing, pp. 365-379

—Saldanha, S.A., Grimm, C., Allais, C., Smith, E., Ouizem, S., Mercer, B.A., Roush, W.R., Heller, S., Hodder, P. (2013) Identification of Selective Agonists of the Transient Receptor Potential Channels 3 (TRPML3). Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-2012 Mar 21 [updated 2013 Sep 03]

—Saldanha, S.A., Grimm, C., Mercer, B.A., Choi, J.Y., Allais, C., Roush, W.R., Heller, S., and Hodder, P. (2011) Campaign to Identify Agonists of Transient Receptor Potential Channels 3 and 2 (TRPML3 & TRPML2), Probe Reports from the NIH Molecular Libraries Program, Bethesda (MD): National Center for Biotechnology Information

# corresponding or shared corresponding author