Dr. Rachel Harding is an Assistant Professor in the Leslie Dan Faculty of Pharmacy at the University of Toronto and a Principal Investigator at the Structural Genomics Consortium (SGC) at University Health Network (UHN). She is cross-appointed to the University of Toronto Department of Pharmacology and Toxicology and is an Affiliate Scientist at the Princess Margaret Cancer Centre. Dr. Harding completed her undergraduate degree (MBiochem) and DPhil at the University of Oxford, where she trained with Dr. Susan Lea, before moving to Toronto for postdoctoral research with Dr. Cheryl Arrowsmith at the SGC. Her postdoctoral work focused on the structure-function of Huntingtin, the protein mutated in Huntington’s disease, supported by a Huntington’s Disease Society of America Berman-Topper Family Career Development Fellowship. Dr. Harding has authored more than 40 peer-reviewed publications and, as an independent investigator, has secured more than $6 million CAD in research funding as Principal Investigator. Her research contributions have been recognised through several awards and honours, including the 2024 Hereditary Disease Foundation Nancy S. Wexler Young Investigator Prize and the 2025 Huntington Society of Canada Michael Wright Community Leadership Award.
The Harding laboratory uses structural biology, protein biochemistry, biophysics and chemical biology to investigate challenging and understudied areas of human biology and disease, particularly where limited molecular understanding or a lack of high-quality chemical tools has constrained therapeutic discovery. The group combines mechanistic studies with ligand discovery and chemical tool development to understand protein function and identify new opportunities for therapeutic intervention. A major focus of the laboratory is repeat expansion disorders, including Huntington’s disease and other polyglutamine diseases. The team studies how disease-associated mutations alter protein structure, interactions, dynamics and biomolecular condensation, and develops chemical tools to interrogate these processes. The laboratory also works on emerging therapeutic targets beyond neurodegeneration, including targets for non-hormonal contraception. Across these research areas, the group aims to develop robust molecular understanding, high-quality chemical tools and openly available datasets and reagents that enable both fundamental discovery and early-stage drug development.
Lepore R, Kryshtafovych A, Alahuhta M, Arora Veraszto H, Bomble YJ, Bufton JC, Bullock AN, Caba C, Cao H, Davies OR, Desfosses A, Dunne M, Fidelis K, Goulding CW, Gurusaran M, Gutsche I, Harding CJ, Hartmann MD, Hayes CS, Joachimiak A, Leiman PG, Loppnau P, Lovering AL, Lunin VV, Michalska K, Mir-Sanchis I, Mitra A, Moult J, Phillips GN, Pinkas DM, Rice PA, Tong Y, Topf M, Walton JD, Schwede T
Proteins. 2019-8-23 . .doi: 10.1002/prot.25805
PMID: 31442339Harding RJ, Loppnau P, Ackloo S, Lemak A, Hutchinson A, Hunt B, Holehouse AS, Ho JC, Fan L, Toledo-Sherman L, Seitova A, Arrowsmith CH
J. Biol. Chem.. 2019-3-6 . .doi: 10.1074/jbc.RA118.007204
PMID: 30842263Harding RJ
PLoS Biol. 2019-1-29 . 17(1):e3000120 .doi: 10.1371/journal.pbio.3000120
PMID: 30689629Ferreira de Freitas R, Harding RJ, Franzoni I, Ravichandran M, Mann MK, Ouyang H, Lautens M, Santhakumar V, Arrowsmith CH, Schapira M
J. Med. Chem.. 2018-5-9 . .doi: 10.1021/acs.jmedchem.8b00258
PMID: 29741882Harding RJ, Tong YF
Acta Pharmacol Sin. 2018-4-6 . 39(5):754-769 .doi: 10.1038/aps.2018.11
PMID: 29620053Zhang H, Zhou B, Qin S, Xu J, Harding R, Tempel W, Nayak V, Li Y, Loppnau P, Dou Y, Min J
Genes Dev.. 2018-3-21 . .doi: 10.1101/gad.311639.118
PMID: 29563185Harding RJ, Ferreira de Freitas R, Collins PM, Franzoni I, Ravichandran M, Ouyang H, Juarez-Ornelas KA, Lautens M, Schapira M, von Delft F, Santhakumar V, Arrowsmith CH
J. Med. Chem.. 2017-10-11 . .doi: 10.1021/acs.jmedchem.7b00933
PMID: 29019676Baker DA, Stewart LB, Large JM, Bowyer PW, Ansell KH, Jiménez-Díaz MB, El Bakkouri M, Birchall K, Dechering KJ, Bouloc NS, Coombs PJ, Whalley D, Harding DJ, Smiljanic-Hurley E, Wheldon MC, Walker EM, Dessens JT, Lafuente MJ, Sanz LM, Gamo FJ, Ferrer SB, Hui R, Bousema T, Angulo-Barturén I, Merritt AT, Croft SL, Gutteridge WE, Kettleborough CA, Osborne SA
Nat Commun. 2017-9-5 . 8(1):430 .doi: 10.1038/s41467-017-00572-x
PMID: 28874661Zhang Q, Wang Z, Hou F, Harding R, Huang X, Dong A, Walker JR, Tong Y
Biochim. Biophys. Acta. 2016-10-21 . .doi: 10.1016/j.bbagen.2016.10.019
PMID: 27776223Zhang Q, Harding R, Hou F, Dong A, Walker JR, Bteich J, Tong Y
J. Biol. Chem.. 2016-6-2 . .doi: 10.1074/jbc.M116.740787
PMID: 27255711