My research investigates the regulatory mechanisms of an important cellular enzyme: AMP-activated protein kinase (AMPK). My goal is to understand how AMPK cooperates with upstream regulator and downstream effector molecules to act as a cellular ‘detection system’ that senses the availability of nutrients and environmental stressors.
AMPK, the master regulator of cellular energy homeostasis, is an attractive drug target for diseases such as type 2 diabetes, cancer, cardiovascular and neurodegenerative diseases. A key aspect of my research is deciphering the molecular mechanisms underlying cell death processes associated with neurological conditions (e.g. brain cell damage following an acute ischaemic stroke).
I study how to improve ischaemic stroke outcomes by restricting AMPK hyperactivity (using small molecule drugs) in animal models of stroke. I utilise state-of-the-art mass-spectrometry-based quantitative phosphoproteomics, together with targeted biochemical approaches in cellular and animal model systems to address my research questions.
Key achievements
2022 International Society for Neurochemistry Travel Award; SVI Discovery Fund Fellowship
2020 SVI Rising Star Award
2019 Human Proteome Organisation Early Career Researcher Travel Award; Harold Mitchell Foundation Travel Fellowship
2018 Selected as attendee at the 2nd International Society for Neurochemistry / Journal of Neurochemistry Flagship School (Austria); ASBMB Travel Fellowship to attend the IUBMB-Advanced School (Thailand)
2015 FAOBMB Travel Fellowship, Young Scientist Program and 14th FAOBMB Congress (India)
2012 Melbourne International Research and Fee Remission Scholarships (MIRS and MIFRS), The University of Melbourne
Selected publications
Morrison KR, Smiles WJ, Ling NXY, HOQUE A, Shea G, Ngoei KRW, Yu D, Murray-Segal L, Scott JW, Galic S, Kemp B, Petersen J and Oakhill JS (2022). An AMPKα2-specific phospho-switch controls lysosomal targeting for activation. Cell Reports 38(7), 110365.
Ling NXY*, Kaczmarek A*, HOQUE A*, Davie E*, Ngoei KRW*, Morrison KR, Smiles WJ, Forte GM, Wang T, Lie S, Dite TA, Langendorf CG, Scott JW, Oakhill JS, and Petersen J (2020). mTORC1 directly inhibits AMPK to promote cell proliferation under nutrient stress. Nature Metabolism 2(1), 41-49. *Co-first author.
HOQUE A, Williamson NA, Ameen SS, Ciccotosto GD, Hossain MI, Oakhill JS, Ng DCH, Ang CS and Cheng HC (2019). Quantitative proteomic analyses of dynamic signalling events in cortical neurons undergoing excitotoxic cell death. Cell Death & Disease 10(3), 1-19.
Dite TA, Langendorf CG, HOQUE A, Galic S, Rebello RJ, Ovens AJ, Lindqvist LM, Ngoei KRW, Ling NXY, Furic L, Kemp BE, Scott JW and Oakhill JS (2018). AMP-activated protein kinase selectively inhibited by the type II inhibitor SBI-0206965. The Journal of Biological Chemistry 293, 8874-8885.
HOQUE A, Sivakumaran P, Bond ST, Ling NXY, Kong AM, Scott JW, Bandara N, Hernandez D, Liu GS, Wong RCB, Ryan MT, Hausenloy DJ, Kemp BE, Oakhill JS, Drew BG, Pebay A and Lim SY (2018). Mitochondrial fission protein Drp1 inhibition promotes cardiac mesodermal differentiation of human pluripotent stem cells. Cell Death Discovery 4(1), 1-13.
HOQUE A, Hossain MI, Ameen SS, Ang CS, Williamson N, Ng DC, Chueh AC, Roulston C and Cheng HC (2016). A beacon of hope in stroke therapy-Blockade of pathologically activated cellular events in excitotoxic neuronal death as potential neuroprotective strategies. Pharmacology & Therapeutics 160, 159-179.
ORCID profile: https://orcid.org/0000-0003-2384-2983
Google Scholar profile: https://scholar.google.com.au/citations?user=bEAmnqYAAAAJ&hl=en
Metabolic Signalling
We investigate how cells maintain their fuel levels to function and grow properly. This knowledge can be used to design better treatments for diabetes, heart disease and cancer.
Lab head: Associate Professor Jon Oakhill