Prof David Komander, Division Head | WEHI Researcher Profile

About

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.

Education

Joint appointments

Publications

Selected publications from Prof David Komander

Gan ZY, Komander D, Callegari S. Reassessing kinetin’s effect on PINK1 and mitophagy. Autophagy. 2024;20(11):10.1080/15548627.2024.2395144

Michel MA, Scutts S, Komander D. Secondary interactions in ubiquitin-binding domains achieve linkage or substrate specificity. Cell Reports. 2024;43(8):10.1016/j.celrep.2024.114545

Nguyen-Dien GT, Townsend B, Kulkarni PG, Kozul K-L, Ooi SS, Eldershaw DN, Weeratunga S, Liu M, Jones MJ, Millard SS, Ng DC, Pagano M, Bonfim-Melo A, Schneider T, Komander D, Lazarou M, Collins BM, Pagan JK. PPTC7 antagonizes mitophagy by promoting BNIP3 and NIX degradation via SCFFBXL4. EMBO Reports. 2024;25(8):10.1038/s44319-024-00181-y

Wu X, Go M, Nguyen JV, Kuchel NW, Lu BGC, Zeglinski K, Lowes KN, Calleja DJ, Mitchell JP, Lessene G, Komander D, Call ME, Call MJ. Mutational profiling of SARS-CoV-2 papain-like protease reveals requirements for function, structure, and drug escape. Nature Communications. 2024;15(1):10.1038/s41467-024-50566-9

Davidson S, Shibata Y, Collard S, Zheng H, Kong K, Sun JM, Laohamonthonkul P, Cerra A, Kratina T, CIRCA, AADRY, Li MWY, Russell C, van Beek A, Kirk EP, Walsh R, Alqanatish J, Almojali A, Alsuwairi W, Alrasheed A, Lalaoui N, Gray PE, Komander D, Masters SL. Dominant negative OTULIN-related autoinflammatory syndrome. Journal of Experimental Medicine. 2024;221(6):10.1084/jem.20222171

Lechtenberg BC, Komander D. Just how big is the ubiquitin system?. Nature Structural & Molecular Biology. 2024;31(2):10.1038/s41594-023-01208-z

Gan ZY, Callegari S, Nguyen TN, Kirk NS, Leis A, Lazarou M, Dewson G, Komander D. Interaction of PINK1 with nucleotides and kinetin. Science Advances. 2024;10(3):10.1126/sciadv.adj7408

Frank D, Bergamasco M, Mlodzianoski MJ, Kueh A, Tsui E, Hall C, Kastrappis G, Voss AK, McLean C, Faux M, Rogers KL, Tran B, Vincan E, Komander D, Dewson G, Tran H. Trabid patient mutations impede the axonal trafficking of adenomatous polyposis coli to disrupt neurite growth. eLife. 2023;12:10.7554/elife.90796

Dewson G, Eichhorn PJA, Komander D. Deubiquitinases in cancer. Nature Reviews Cancer. 2023;23(12):10.1038/s41568-023-00633-y

Wilde M-L, Ruparel U, Klemm T, Lee VV, Calleja DJ, Komander D, Tonkin CJ. Characterisation of the OTU domain deubiquitinase complement of Toxoplasma gondii. Life Science Alliance. 2023;6(6):10.26508/lsa.202201710