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  • Dario Alessi
2018

The Parkinson's disease VPS35[D620N] mutation enhances LRRK2 mediated Rab protein phosphorylation in mouse and human

Mir, R., Tonelli, F., Lis, P., Macartney, T., Polinski, N. K., Martinez, T. N., Chou, M-Y., Howden, A., König, T., Hotzy, C., Milenkovic, I., Brücke, T., Zimprich, A., Sammler, E. & Alessi, D., 6 Jun 2018, In : Biochemical Journal. 475, 11, p. 1861-1883 19 p.

Research output: Contribution to journalArticle

Open Access
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41 Citations (Scopus)
176 Downloads (Pure)

Mechanism of activation of SGK3 by growth factors-via the Class 1 and Class 3 PI3Ks

Malik, N., Macartney, T., Hornberger, A., Anderson, K., Tovell, H., Prescott, A. R. & Alessi, D. R., 2 Jan 2018, In : Biochemical Journal. 475, 1, p. 117-135 19 p.

Research output: Contribution to journalArticle

Open Access
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10 Citations (Scopus)
249 Downloads (Pure)
2017

Regulation of membrane ruffling by polarized STIM1 and ORAI1in cortactin-rich domains

M. López-Guerrero, A., Tomas-Martin, P., Pascual-Caro, C., Macartney, T., Rojas-Fernandez, A., Ball, G., Alessi, D. R., Pozo-Guisado, E. & Martin-Romero, F. J., 24 Mar 2017, In : Scientific Reports. 7, 15 p., 383.

Research output: Contribution to journalArticle

Open Access
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8 Citations (Scopus)
125 Downloads (Pure)
2019

Rapid and reversible knockdown of endogenously tagged endosomal proteins via an optimized HaloPROTAC degrader

Tovell, H., Testa, A., Maniaci, C., Zhou, H., Prescott, A., Macartney, T., Ciulli, A. & Alessi, D., 17 May 2019, In : ACS Chemical Biology. 14, 5, p. 882-892 11 p.

Research output: Contribution to journalArticle

Open Access
File
9 Citations (Scopus)
162 Downloads (Pure)
2017

Integrated single-cell genetic and transcriptional analysis suggests novel drivers of chronic lymphocytic leukemia

Wang, L., Fan, J., Francis, J. M., Georghiou, G., Hergert, S., Li, S., Gambe, R., Zhou, C. W., Yang, C., Xiao, S., Cin, P. D., Bowden, M., Kotliar, D., Shukla, S. A., Brown, J. R., Neuberg, D., Alessi, D. R., Zhang, C-Z., Kharchenko, P. V., Livak, K. J. & 1 others, Wu, C. J., 5 Jul 2017, In : Genome Research. 27, p. 1300-1311 11 p.

Research output: Contribution to journalArticle

Open Access
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25 Citations (Scopus)
163 Downloads (Pure)

Vomocytosis of live pathogens from macrophages is regulated by the atypical MAP kinase ERK5

Gilbert, A. S., Seoane, P. I., Sephton-Clark, P., Bojarczuk, A., Hotham, R., Giurisato, E., Sarhan, A. R., Hillen, A., Velde, G. V., Gray, N. S., Alessi, D. R., Cunningham, D. L., Tournier, C., Johnston, S. A. & May, R. C., 16 Aug 2017, In : Science Advances. 3, 8, p. 1-9 9 p., e1700898.

Research output: Contribution to journalArticle

Open Access
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22 Citations (Scopus)
153 Downloads (Pure)
2016

Functional kinomics establishes a critical node of volume-sensitive cation-Cl- cotransporter regulation in the mammalian brain

Zhang, J., Gao, G., Begum, G., Wang, J., Khanna, A. R., Shmukler, B. E., Daubner, G. M., De Los Heros, P., Davies, P., Varghese, J., Bhuiyan, M. I. H., Duan, J., Zhang, J., Duran, D., Alper, S. L., Sun, D., Elledge, S. J., Alessi, D. R. & Kahle, K. T., 26 Oct 2016, In : Scientific Reports. 6, p. 1-19 19 p., 35986.

Research output: Contribution to journalArticle

Open Access
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14 Citations (Scopus)
147 Downloads (Pure)
2018

A pathway for Parkinson's Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain

Dhekne, H. S., Yanatori, I., Gomez, R. C., Tonelli, F., Diez, F., Schüle, B., Steger, M., Alessi, D. R. & Pfeffer, S. R., 6 Nov 2018, In : eLife. 7, p. 1-26 26 p., e40202.

Research output: Contribution to journalArticle

Open Access
File
29 Citations (Scopus)
145 Downloads (Pure)

Structural and Atropisomeric Factors Governing the Selectivity of Pyrimido-benzodiazipinones as Inhibitors of Kinases and Bromodomains

Wang, J., Erazo, T., Ferguson, F. M., Buckley, D. L., Gomez, N., Muñoz-Guardiola, P., Diéguez-Martínez, N., Deng, X., Hao, M., Massefski, W., Fedorov, O., Offei-Addo, N. K., Park, P. M., Dai, L., DiBona, A., Becht, K., Kim, N. D., McKeown, M. R., Roberts, J. M., Zhang, J. & 8 others, Sim, T., Alessi, D. R., Bradner, J. E., Lizcano, J. M., Blacklow, S. C., Qi, J., Xu, X. & Gray, N. S., 21 Sep 2018, In : ACS Chemical Biology. 13, 9, p. 2438-2448 11 p.

Research output: Contribution to journalArticle

Open Access
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9 Citations (Scopus)
173 Downloads (Pure)
2016

PDK1-SGK1 signaling sustains AKT-independent mTORC1 activation and confers resistance to PI3Kα inhibition

Castel, P., Ellis, H., Bago, R., Toska, E., Razavi, P., Carmona, F. J., kannan, S., Verma, C. S., Dickler, M., Chandarlapaty, S., Brogi, E., Alessi, D., Baselga, J. & Scaltriti, M., 8 Aug 2016, In : Cancer Cell. 30, 2, p. 229-242 14 p.

Research output: Contribution to journalArticle

Open Access
File
72 Citations (Scopus)
315 Downloads (Pure)
2019

PPM1H phosphatase counteracts LRRK2 signaling by selectively dephosphorylating Rab proteins

Berndsen, K., Lis, P., Yeshaw, W. M., Wawro, P. S., Nirujogi, R., Wightman, M., Macartney, T., Dorward, M., Knebel, A., Tonelli, F., Pfeffer, S. R. & Alessi, D., 30 Oct 2019, In : eLife. 8, p. 1-37 37 p., e50416.

Research output: Contribution to journalArticle

Open Access
File
6 Citations (Scopus)
57 Downloads (Pure)
2017

Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis

Steger, M., Diez, F., Dhekne, H. S., Lis, P., Nirujogi, R. S., Karayel, O., Tonelli, F., Martinez, T. N., Lorentzen, E., Pfeffer, S. R., Alessi, D. R. & Mann, M., 10 Nov 2017, In : eLife. 6, p. 1-22 22 p., e31012.

Research output: Contribution to journalArticle

Open Access
File
92 Citations (Scopus)
244 Downloads (Pure)
2020

Structural Basis for Rab8a Recruitment of RILPL2 via LRRK2 Phosphorylation of Switch 2

Waschbüsch, D., Purlyte, E., Pal, P., McGrath, E., Alessi, D. R. & Khan, A. R., 7 Apr 2020, In : Structure. 28, 4, p. 406-417.e6 19 p.

Research output: Contribution to journalArticle

Open Access
File
1 Citation (Scopus)
43 Downloads (Pure)
2016

Phos-tag analysis of Rab10 phosphorylation by LRRK2: a powerful assay for assessing kinase function and inhibitors

Ito, G., Katsemonova, K., Tonelli, F., Lis, P., Baptista, M., Shpiro, N., Duddy, G., Wilson, S., Wing-Lok Ho, P., Ho, S-L., Reith, A. D. & Alessi, D., 30 Aug 2016, In : Biochemical Journal. 473, 17, p. 2671-2685 15 p.

Research output: Contribution to journalArticle

Open Access
File
56 Citations (Scopus)
251 Downloads (Pure)
2019

Discovery of potent and selective 5-azaindazole inhibitors of leucine-rich repeat kinase 2 (LRRK2) - Part 1

Osborne, J., Birchall, K., Tsagris, D. J., Lewis, S. J., Smiljanic-Hurley, E., Taylor, D. L., Levy, A., Alessi, D. & McIver, E. G., 15 Feb 2019, In : Bioorganic & Medicinal Chemistry Letters. 29, 4, p. 668-673 6 p.

Research output: Contribution to journalArticle

Open Access
File
61 Downloads (Pure)
2020

Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson’s Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation

Fan, Y., Tonelli, F., Padmanabhan, S., Baptista, M., Riley, L., Smith, D., Marras, C., Howden, A., Alessi, D. & Sammler, E., 22 Mar 2020, In : JoVE: Journal of Visualized Experiments. 157, e58956.

Research output: Contribution to journalArticle

2016

Phosphoproteomics reveals that Parkinson’s disease kinase LRRK2 regulates a subset of Rab GTPases

Steger, M., Tonelli, F., Ito, G., Davies, P., Trost, M., Vetter, M., Wachter, S., Lorentzen, E., Duddy, G., Wilson, S., Baptista, M. A. S., Fiske, B. K., Fell, M. J., Morrow, J. A., Reith, A. D., Alessi, D. R. & Mann, M., 29 Jan 2016, In : eLife. 5, p. 1-28 28 p., e12813.

Research output: Contribution to journalArticle

Open Access
File
302 Citations (Scopus)
234 Downloads (Pure)
2017

USP7 small-molecule inhibitors interfere with ubiquitin binding

Kategaya, L., Di Lello, P., Rougé, L., Pastor, R., Clark, K. R., Drummond, J., Kleinheinz, T., Lin, E., Upton, J-P., Prakash, S., Heideker, J., McCleland, M., Ritorto, M. S., Alessi, D. R., Trost, M., Bainbridge, T. W., Kwok, M. C. M., Ma, T. P., Stiffler, Z., Brasher, B. & 24 others, Tang, Y., Jaishankar, P., Hearn, B. R., Renslo, A. R., Arkin, M. R., Cohen, F., Yu, K., Peale, F., Gnad, F., Chang, M. T., Klijn, C., Blackwood, E., Martin, S. E., Forrest, W. F., Ernst, J. A., Ndubaku, C., Wang, X., Beresini, M. H., Tsui, V., Schwerdtfeger, C., Blake, R. A., Murray, J., Maurer, T. & Wertz, I. E., 18 Oct 2017, In : Nature. 550, p. 534-538 5 p.

Research output: Contribution to journalLetter

Open Access
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89 Citations (Scopus)
544 Downloads (Pure)
2018

Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils

Fan, Y., Howden, A. J. M., Sarhan, A. R., Lis, P., Ito, G., Martinez, T. N., Brockmann, K., Gasser, T., Alessi, D. R. & Sammler, E., 2 Jan 2018, In : Biochemical Journal. 475, 1, p. 23-44 22 p.

Research output: Contribution to journalArticle

Open Access
File
37 Citations (Scopus)
189 Downloads (Pure)

Development of phospho-specific Rab protein antibodies to monitor in vivo activity of the LRRK2 Parkinson’s disease kinase

Lis, P., Burel, S., Steger, M., Mann, M., Brown, F., Diez, F., Tonelli, F., Holton, J. L., Winglok Ho, P., Ho, S-L., Chou, M-Y., Polinski, N. K., Martinez, T. N., Davies, P. & Alessi, D. R., 2 Jan 2018, In : Biochemical Journal. 475, 1, p. 1-22 22 p.

Research output: Contribution to journalArticle

Open Access
File
29 Citations (Scopus)
290 Downloads (Pure)
2019

Membrane association but not identity is required for LRRK2 activation and phosphorylation of Rab GTPases

Gomez, R. C., Wawro, P., Lis, P., Alessi, D. & Pfeffer, S. R., 2 Dec 2019, In : Journal of Cell Biology. 218, 12, p. 4157-4170 14 p.

Research output: Contribution to journalArticle

Open Access
File
79 Downloads (Pure)
2018

LRRK2 kinase in Parkinson's disease

Alessi, D. R. & Sammler, E., 6 Apr 2018, In : Science. 360, 6384, p. 36-37 2 p.

Research output: Contribution to journalComment/debate

Open Access
File
61 Citations (Scopus)
384 Downloads (Pure)

PP1 Phosphatase complexes: Undruggable No Longer

Vagnarelli, P. & Alessi, D. R., 23 Aug 2018, In : Cell. 174, 5, p. 1049-1051 3 p.

Research output: Contribution to journalArticle

Open Access
File
2 Citations (Scopus)
90 Downloads (Pure)
2019

Crystal structure of the WD40 domain dimer of LRRK2

Zhang, P., Fan, Y., Ru, H., Wang, L., Magupalli, V. G., Taylor, S. S., Alessi, D. R. & Wu, H., 29 Jan 2019, In : Proceedings of the National Academy of Sciences of the United States of America. 116, 5, p. 1579-1584 6 p.

Research output: Contribution to journalArticle

Open Access
File
6 Citations (Scopus)
137 Downloads (Pure)
2018

LRRK2 activation in idiopathic Parkinson's disease

Di Maio, R., Hoffman, E. K., Rocha, E. M., Keeney, M. T., Sanders, L. H., De Miranda, B. R., Zharikov, A., Van Laar, A., Stepan, A. F., Lanz, T. A., Kofler, J. K., Burton, E. A., Alessi, D. R., Hastings, T. G. & Timothy Greenamyre, J., 25 Jul 2018, In : Science Translational Medicine. 10, 451, p. 1-12 12 p., eaar5429.

Research output: Contribution to journalArticle

Open Access
File
70 Citations (Scopus)
89 Downloads (Pure)

Nigrostriatal pathology with reduced astrocytes in LRRK2 S910/S935 phosphorylation deficient knockin mice

Zhao, Y., Keshiya, S., Atashrazm, F., Gao, J., Ittner, L. M., Alessi, D. R., Halliday, G. M., Fu, Y. & Dzamko, N., 1 Dec 2018, In : Neurobiology of Disease. 120, p. 76-87 12 p.

Research output: Contribution to journalArticle

Open Access
File
4 Citations (Scopus)
167 Downloads (Pure)
2019

Phosphoproteomics reveals that the hVPS34 regulated SGK3 kinase specifically phosphorylates endosomal proteins including Syntaxin-7, Syntaxin-12, RFIP4 and WDR44

Malik, N., Nirujogi, R. S., Peltier, J., Macartney, T., Wightman, M., Prescott, A., Gourlay, R., Trost, M., Alessi, D. & Karapetsas, A., 30 Oct 2019, In : Biochemical Journal. 476, 20, p. 3081-3107 27 p.

Research output: Contribution to journalArticle

Open Access
File
59 Downloads (Pure)
2017

Small-Molecule Inhibitors of LRRK2

Hatcher, J. M., Choi, H. G., Alessi, D. R. & Gray, N. S., 2017, Leucine-Rich Repeat Kinase 2 (LRRK2). Rideout, H. J. (ed.). Springer International Publishing, p. 241-264 24 p. (Advances in neurobiology; vol. 14).

Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)

14 Citations (Scopus)

Homo-PROTACs: bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase to induce self-degradation

Maniaci, C., Hughes, S. J., Testa, A., Chen, W., Lamont, D. J., Rocha, S., Alessi, D. R., Romeo, R. & Ciulli, A., 10 Oct 2017, In : Nature Communications. 8, p. 1-14 14 p., 830.

Research output: Contribution to journalArticle

Open Access
File
58 Citations (Scopus)
186 Downloads (Pure)
2020

Accurate MS-based Rab10 phosphorylation stoichiometry determination as readout for LRRK2 activity in Parkinson's disease

Karayel, O., Tonelli, F., Virreira Winter, S., Geyer, P. E., Fan, Y., Sammler, E. M., Alessi, D., Steger, M. & Mann, M., 29 Jun 2020, In : Molecular & Cellular Proteomics.

Research output: Contribution to journalArticle

Open Access
File
6 Downloads (Pure)
2016

The hVPS34-SGK3 pathway counteracts inhibition of the PI3K-Akt to maintain mTORC1 and tumour growth

Bago, R., Eskelinen, E-L., Castel, P., Crafter, C., Bailey, F. P., Shpiro, N., Baselga, J., Cross, D., Eyers, P. & Alessi, D., 1 Sep 2016, In : EMBO Journal. 35, 17, p. 1902-1922 23 p.

Research output: Contribution to journalArticle

Open Access
File
28 Citations (Scopus)
154 Downloads (Pure)
2019

Design and Characterization of SGK3-PROTAC1, an Isoform Specific SGK3 Kinase PROTAC Degrader

Tovell, H., Testa, A., Zhou, H., Shpiro, N., Crafter, C., Ciulli, A. & Alessi, D., 20 Sep 2019, In : ACS Chemical Biology. 14, 9, p. 2024-2034 11 p.

Research output: Contribution to journalArticle

Open Access
File
6 Citations (Scopus)
100 Downloads (Pure)
2018

LRRK2 is a negative regulator of Mycobacterium tuberculosis phagosome maturation in macrophages

Härtlova, A., Herbst, S., Peltier, J., Rodgers, A., Bilkei-Gorzo, O., Fearns, A., Dill, B. D., Lee, H., Flynn, R., Cowley, S. A., Davies, P., Lewis, P. A., Ganley, I. G., Martinez, J., Alessi, D. R., Reith, A. D., Trost, M. & Gutierrez, M. G., 15 Jun 2018, In : The EMBO Journal. 37, 12, p. 1-17 17 p., e98694.

Research output: Contribution to journalArticle

Open Access
File
45 Citations (Scopus)
182 Downloads (Pure)
2020
Open Access
File
2 Citations (Scopus)
56 Downloads (Pure)
2017

Rab29 activation of the Parkinson's disease-associated LRRK2 kinase

Purlyte, E., Dhekne, H. S., Sarhan, A. R., Gomez, R., Lis, P., Wightman, M., Martinez, T. N., Tonelli, F., Pfeffer, S. R. & Alessi, D. R., 15 Dec 2017, In : EMBO Journal. 36, 24, p. 3549-3681 18 p., e201798099.

Research output: Contribution to journalArticle

Open Access
File
62 Citations (Scopus)
225 Downloads (Pure)
2018

Disruption of the with no lysine kinase-STE20-proline alanine-rich kinase pathway reduces the hypertension induced by angiotensin II

Graciela Cervantes-Perez, L., Castaneda-Bueno, M., Jimenez, J. V., Vazquez, N., Rojas-Vega, L., Alessi, D., Bobadilla, N. A. & Gamba, G., 1 Feb 2018, In : Journal of Hypertension. 36, 2, p. 361-367 7 p.

Research output: Contribution to journalArticle

Open Access
File
1 Citation (Scopus)
191 Downloads (Pure)
2017

B cell-intrinsic function of TAPP adaptors in controlling germinal center responses and autoantibody production in mice

Jayachandran, N., Landego, I., Hou, S., Alessi, D. R. & Marshall, A. J., 10 Feb 2017, In : European Journal of Immunology. 47, 2, p. 280-290 11 p.

Research output: Contribution to journalArticle

Open Access
File
5 Citations (Scopus)
172 Downloads (Pure)