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About

My team focuses on understanding the molecular and co-ordinated control of the two fundamental pathways of apoptosis and mitophagy (mitochondrial quality control) and its importance to Parkinson’s disease and cancer.

Our research has led the field in understanding of how the fundamental cell process of apoptosis is controlled, how the apoptosis effector proteins BAX and BAK function to kill cells and has identified new avenues to manipulate their activity therapeutically.

More recently, my lab has highlighted a new level of integration between the machineries that control cell death and damage-induced mitophagy that might explain why defective activity of the key protein Parkin drives the pathology of early onset Parkinson’s disease. My lab has established and shared new animal and cell models to investigate Parkinson’s disease, mitochondrial biology, and cell death research.

We have established key collaborations with the clinic. With Dr Andrew Evans (Director, Movement Disorders Program, Royal Melbourne Hospital), we have a pipeline for the recruitment of Parkinson’s disease patients and the generation of patient-derived cells (dopaminergic neurons and astrocytes) to understand the disease in individuals and to accelerate clinical translation of our research.

Publications

Selected publications from Prof Grant Dewson

Glover HL, Schreiner A, Dewson G, Tait SWG. Mitochondria and cell death. Nature Cell Biology. 2024;26(9):10.1038/s41556-024-01429-4

Yuan Z, van Delft MF, Li MX, Sumardy F, Smith BJ, Huang DCS, Lessene G, Khakam Y, Jin R, He S, Smith NA, Birkinshaw RW, Czabotar PE, Dewson G. Key residues in the VDAC2-BAK complex can be targeted to modulate apoptosis. PLOS Biology. 2024;22(5):10.1371/journal.pbio.3002617

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.90796.3

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

Birkinshaw RW, Iyer S, Lio D, Luo C, Brouwer J, Miller MS, Robin A, Uren RT, Dewson G, Kluck RM, Colman PM, Czabotar PE. The crystal structure of detergent-activated BAK dimers provides insights into BAK activation steps and how they stabilise membrane pores. Acta Crystallographica Section A: Foundations and advances. 2023;79(a2):10.1107/s205327332308912x

Huang AS, Chin HS, Reljic B, Djajawi TM, Tan IKL, Gong J-N, Stroud DA, Huang DCS, van Delft MF, Dewson G. Mitochondrial E3 ubiquitin ligase MARCHF5 controls BAK apoptotic activity independently of BH3-only proteins. Cell Death & Differentiation. 2023;30(3):10.1038/s41418-022-01067-z

Masaldan S, Callegari S, Dewson G. Therapeutic targeting of mitophagy in Parkinson’s disease. Biochemical Society Transactions. 2022;50(2):10.1042/bst20211107

Gan ZY, Callegari S, Cobbold SA, Cotton TR, Mlodzianoski MJ, Schubert AF, Geoghegan ND, Rogers KL, Leis A, Dewson G, Glukhova A, Komander D. Publisher Correction: Activation mechanism of PINK1. Nature. 2022;603(7903):10.1038/s41586-022-04591-7

Lab research projects

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