We focus on the modifier ubiquitin, a small protein that modifies other proteins in a variety of distinct ways, known as the ‘ubiquitin code’.

Ubiquitination most commonly leads to destruction of the modified protein, but can also change its activation, interactions or localisation. Much of our work aims to enable studies of ubiquitin signals.

A biological focus of the lab are deubiquitinases (DUBs) that remove ubiquitin from proteins. Using structural biology and biophysics, we have unraveled many mechanistic and regulatory principles of how DUBs cleave ubiquitin modifications.

Using preclinical models and in collaboration with human geneticists, we ascribe cellular and physiological function to select enzymes. Finally, in collaboration with industry, we are developing the first enzyme-specific DUB inhibitors, which may become new treatments for cancer and neurodegeneration.


Selected publications from Prof David Komander

Gladkova C, Maslen S, Skehel LM, Komander D. Mechanism of Parkin activation by PINK1. Nature. 2018 Jul;559(7714):410-414. Epub 2018 Jun 6. PMID: 29995846

Schubert AF, Gladkova C, Pardon E, Steyaert J, Maslen SL, Komander D. Structure of PINK1 in complex with its substrate ubiquitin. Nature. 2017 Dec 7; 552(7683): 51-56. PMID: 29160309

Turnbull AP, Ioannidis S, Krajewski WW, Pinto-Fernandez A, Martin ACL, Tonkin LM, Townsend EC, Buker SM, Heride C, Lancia Jr. DR, Caravella JR, Toms AV, Charlton TM, Lahdenranta J, Wilker E, Follows BC, Evans NJ, Stead L, Alli C, Zarayskiy ZZ, Talbot AC, Buckmelter AJ, Wang M, McKinnon CL, Saab F , McGouran JF, Century H, Gersch M, Pittman MS, Marshall CG, Raynham TM, Simcox M, Stewart LMD, McLoughlin SB, Escobedo JA, Bair KW, Dinsmore CJ, Hammonds TR, Kim S, Urbé S, Clague MJ, Kessler BM, Komander D. Molecular basis of USP7 inhibition by selective small molecule inhibitors. Nature (2017) Oct 26; 550(7677): 481-486. PMID: 29045389

Gersch M, Gladkova C$, Schubert AF$, Michel MA, Maslen SL, Komander D. Mechanism and regulation of the Lys6-selective deubiquitinase USP30. Nat Struct Mol Biol. 2017 Nov; 24(11): 920-930. PMID: 28945249

Mevissen TET, Kulathu Y, Mulder MPC, Geurink PP, Maslen SL, Gersch M, Elliott PR, Burke JE, van Tol BDM, Akutsu M, El Oualid F, Kawasaki M, Freund SMV, Ovaa H and Komander D. Molecular basis for Lys11-polyubiquitin specificity in Cezanne/OTUD7B. Nature. 2016 Oct 20; 538(7625): 402-405. PMID: 27732584

Damgaard RB, Walker JA, Marco-Casanova P, Morgan NV, Titheradge HL, Elliott PR, McHale D, Maher ER, McKenzie ANJ, Komander D. The deubiquitinase OTULIN is an essential negative regulator of inflammation and autoimmunity. Cell. 2016 Aug 25; 166(5): 1215-1230. Epub Aug 11 PMID: 27523608

Wauer T, Simicek M, Schubert A, Komander D. Mechanism of phospho-ubiquitin induced Parkin activation. Nature. 2015 Aug 20; 524(7565): 370-4. PMID: 26161729

Mevissen TET, Hospenthal MK, Geurink PP, Elliott PR, Akutsu M, Arnaudo N, Ekkebus R, Kulathu Y, Wauer T, El Oualid F, Freund SMV, Ovaa H, Komander D. OTU domain deubiquitinases reveal mechanisms of linkage-specificity and enable ubiquitin chain restriction analysis. Cell. 2013 Jul 3; 154(1): 169-84. PMID: 23827681

Keusekotten K, Elliott PR, Glockner L, Fiil BK, Damgaard RB, Kulathu Y, Wauer T, Hospenthal MK, Gyrd-Hansen M, Krappmann D, Hofmann K, Komander D. OTULIN antagonizes LUBAC ignalling by specifically hydrolysing Met1-linked polyubiquitin. Cell. 2013 Jun 6; 153(6): 1312-26 PMID: 23746843

Lab research projects

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