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A/Prof Jonathan Oakhill

Research Unit

Metabolic signalling

Information

Protein Chemistry and Metabolism Unit

Professional Experience

1998 BSc (Hons) Bath University, UK
2002 PhD Biochemistry, King’s College London, UK
2002-2006 Postdoctoral Fellow, School of Biomedical and Health Science, King’s College
2006-Present Research Fellow, SVI
2014-17 ARC Future Fellow

Achievements

Research Interests

My research aims to define mechanisms mediating energy-sensing by the master metabolic regulator AMP-activated protein kinase (AMPK), a key regulator of cellular and systemic energy homeostasis. The metabolic dimensions of diseases including type 2 diabetes, obesity, cardiovascular disease and cancer, have encouraged efforts to develop direct activating drugs for AMPK. Co-ordinating biochemical, crystallographic, mass spectrometry and cell-based projects running in the Kemp group, my research has provided significant breakthroughs in understanding the complex regulatory mechanisms that enable AMPK to perform its critical roles. These findings form the foundations to strategies aimed at developing novel therapeutics to treat diseases that impose enormous medical and economical burdens.

Selected Publications

  1. 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* & Petersen J*. mTORC1 directly inhibits AMPK to promote cell proliferation under nutrient stress. *co-senior authors. Nature Metabolism, 2:41-49 (2020).
  2. Vrahnas C, Blank M, Dite TA, Tatarczuch L, Ansari N, Crimeen-Irwin B, Nguyen H, Forwood MR, Hu Y, Ikegame M, Bambery KR, Petibois C, Mackie EJ, Tobin MJ, Smyth GK, Oakhill JS, Martin TJ & Sims NA. Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone. Nature Communications, 10:3436 (2019).
  3. Dite TA, Langendorf CG, Hoque A, Galic S, Rebello RJ, Ovens AJ, Lindqvist LM, Ngoei KRW, Ling NXY, Furic L, Kemp BE, Scott JW & Oakhill JS. AMP-activated protein kinase selectively inhibited by the type II inhibitor SBI-0206965. Journal of Biological Chemistry, 293:8874-8885 (2018).
  4. Ngoei KRW, Langendorf CG, Ling NXY, Hoque A, Varghese S, Camerino MA, Walker SR, Bozikis YE, Dite TA, Ovens AJ, Smiles WJ, Jacobs R, Huang H, Parker MW, Scott JW, Rider MH, Foitzik RC, Kemp BE, Baell JB & Oakhill JS. Structural Determinants for Small-Molecule Activation of Skeletal Muscle AMPK α2β2γ1 by the Glucose Importagog SC4. Cell Chemical Biology, 25:728-737 (2018).
  5. Dite TA, Ling NXY, Scott JW, Hoque A, Galic S, Parker BL, Ngoei KRW, Langendorf CG, O’Brien MT, Kundu M, Viollet B, Steinberg GR, Sakamoto K, Kemp BE, Oakhill JS. The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs. Nature Communications, 8:571 (2017).
  6. Langendorf CG, Ngoei KR, Scott JW, Ling NX, Issa SM, Gorman MA, Parker MW, Sakamoto K, Oakhill JS & Kemp BE. Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding. Nature Communications, 7:10912 (2016).
  7. Scott JW, Galic S, Graham KL, Foitzik R, Ling NXY, Dite TA, Issa SMA, Langendorf CG, Weng QP, Thomas HE, Kay TWH, Birnberg NC, Steinberg GR, Kemp BE & Oakhill JS. Inhibition of AMP-activated protein kinase at the allosteric drug-binding site promotes islet insulin release. Chemistry & Biology, 22:705-711 (2015).
  8. Scott JW, Ling NXY, Issa SMA, Dite TA, O’Brien MT, Chen ZP, Galic S, Langendorf CG, Steinberg GR, Kemp BE & Oakhill JS. Drugs and AMP unite to switch on naive AMPK. Chemistry & Biology, 21:619-627 (2014).
  9. Oakhill JS, Steel R, Chen ZP, Scott JW, Ling N, Tam S & Kemp BE. AMPK is a direct adenylate charge-regulated protein kinase. Science, 332:1433-1435 (2011).
  10. Oakhill JS, Chen ZP, Scott JW, Steel R, Castelli LA, Ling N, Macaulay SL & Kemp BE. β-Subunit myristoylation is the gatekeeper for initiating metabolic stress sensing by AMP-activated protein kinase (AMPK). PNAS, 107:19237-19241 (2010).