Geoffrey G. Hesketh

Education

• Postdoctoral Fellow, Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario
• Postdoctoral Fellow, University of Cambridge, UK
• PhD, Johns Hopkins University, Baltimore, Maryland
• BScH, Queen's University, Kingston, Ontario

Academic Positions

• Department member since 2022

Research Topics:

Molecular cell biology of lysosome function, mTOR, cancer cell biology, proteomics, mass spectrometry

Research

I am a molecular cell biologist, fascinated by how lysosomes control the balance between anabolic and catabolic pathways in cells. Specifically, I study how nutrients are sensed on the surfaces of lysosomal system organelles and how this is coupled to the activation state of mTORC1, a master growth regulator. mTORC1 in turn broadly controls cellular anabolism (i.e., macromolecular biosynthesis) and catabolism (i.e., macromolecular breakdown). These pathways are central to the pathogenesis of human diseases including mutant Ras-driven cancers (e.g., pancreatic cancer), neurodegeneration, and infectious diseases. In pursuit of these questions I employ proximity-dependent biotinylation and mass spectrometry (e.g., BioID), CRISPR-Cas9 gene editing, and a variety of classical molecular cell biology techniques.

Current Lab Members

Publications

A complete publication list is available on the Hesketh Lab publications page.

1. Go CD, Knight JDR, Rajasekharan A, Rathod B, Hesketh GG, Abe KT, Youn JY, Samavarchi-Tehrani P, Zhang H, Zhu LY, Popiel E, Lambert JP, Coyaud É, Cheung SWT, Rajendran D, Wong CJ, Antonicka H, Pelletier L, Palazzo AF, Shoubridge EA, Raught B and Gingras AC. A proximity-dependent biotinylation map of a human cell. Nature. 2021, 595(7865): 120-124. PMID: 34079125.
2. Hesketh GG, Papazotos F, Pawling J, Rajendran D, Knight JDR, Martinez S, Taipale M, Schramek D, Dennis JW and Gingras AC. The GATOR-Rag GTPase pathway inhibits mTORC1 activation by lysosome-derived amino acids. Science. 2020, 370(6514): 351-356. PMID: 33060361.
3. Hesketh GG, Pérez-Dorado I, Jackson LP, Wartosch L, Schäfer IB, Gray SR, McCoy AJ, Zeldin OB, Garman EF, Harbour ME, Evans PR, Seaman MNJ, Luzio JP and Owen DJ. VARP is recruited on to endosomes by direct interaction with retromer, where together they function in export to the cell surface. Dev Cell. 2014, 29(5): 591-606. PMID: 24856514.
4. Schäfer IB, Hesketh GG, Bright NA, Gray SR, Pryor PR, Evans PR, Luzio JP and Owen DJ. The binding of Varp to VAMP7 traps VAMP7 in a closed, fusogenically inactive conformation. Nat Struct Mol Biol. 2012, 19(12): 1300-9. PMID: 23104059.
5. Hesketh GG, Shah MH, Halperin VL, Cooke CA, Akar FG, Yen TE, Kass DA, Machamer CE, Van Eyk JE and Tomaselli GF. Ultrastructure and regulation of lateralized connexin43 in the failing heart. Circ Res. 2010, 106(6): 1153-63. PMID: 20167932.