Rachel Harding

Rachel Harding

SGC Toronto

Harding

Biography

Dr. Harding is an Assistant Professor in the Faculty of Pharmacy, is a Principal Investigator at the Structural Genomics Consortium and is also cross-appointed to the Department of Pharmacology and Toxicology, all at the University of Toronto. Dr. Harding completed both her undergraduate (MBiochem) and graduate (DPhil) studies at the University of Oxford, the latter training in the lab of Dr. Susan Lea. Dr. Harding moved to the University of Toronto for her postdoctoral training in the lab of Dr. Cheryl Arrowsmith. Dr. Harding was awarded the prestigious Huntington’s Disease Society of America Berman-Topper Family Career Development Fellowship for her research on the structure-function of the Huntington’s disease protein, huntingtin, work that has continued into her independent research career. Her contributions to the field of Huntington’s were further recognised with her award of the 2024 Nancy Wexler Young Investigator Prize, an honour bestowed upon a researcher whose work reflects the highest calibre of excellence, diligence and creative thinking.

Research Areas

Dr. Harding's team uses structural biology, protein biochemistry and chemical biology to study the molecular mechanisms of pathology of repeat expansion disorders, with a primary focus on Huntington’s disease. Huntington’s is a devastating, incurable, genetic, neurodegenerative disease caused by a CAG-tract expansion in the Huntingtin gene. The group is concentrated on three key areas: 1) defining the structure-function relationship of the Huntington’s disease protein, huntingtin, and how this is altered by the disease-causing mutation; 2) molecular mechanisms of repeat expansion disorders like Huntington’s; and 3) development of chemical tools targeting understudied proteins and targets of interest for Huntington’s disease drug discovery.

2020

Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response.

Szewczyk MM, Ishikawa Y, Organ S, Sakai N, Li F, Halabelian L, Ackloo S, Couzens AL, Eram M, Dilworth D, Fukushi H, Harding R, Dela Seña CC, Sugo T, Hayashi K, McLeod D, Zepeda C, Aman A, Sánchez-Osuna M, Bonneil E, Takagi S, Al-Awar R, Tyers M, Richard S, Takizawa M, Gingras AC, Arrowsmith CH, Vedadi M, Brown PJ, Nara H, Barsyte-Lovejoy D

Nat Commun. 2020-5-14 . 11(1):2396 .doi: 10.1038/s41467-020-16271-z

PMID: 32409666

2019

Discovery of small molecule antagonists of the USP5 zinc finger ubiquitin-binding domain.

Mann MK, Franzoni I, de Freitas RF, Tempel W, Houliston S, Smith L, Vedadi M, Arrowsmith CH, Harding RJ, Schapira M

J. Med. Chem.. 2019-10-30 . .doi: 10.1021/acs.jmedchem.9b00988

PMID: 31663737

Target highlights in CASP13: experimental target structures through the eyes of their authors.

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: 31442339

Design and characterization of mutant and wild-type huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems.

Harding 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: 30842263

2018

Identification and Structure-Activity Relationship of HDAC6 Zinc-Finger Ubiquitin Binding Domain Inhibitors.

Ferreira 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: 29741882

Proteostasis in Huntington's disease: disease mechanisms and therapeutic opportunities.

Harding RJ, Tong YF

Acta Pharmacol Sin. 2018-4-6 . 39(5):754-769 .doi: 10.1038/aps.2018.11

PMID: 29620053

Structural and functional analysis of the DOT1L-AF10 complex reveals mechanistic insights into MLL-AF10-associated leukemogenesis.

Zhang 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: 29563185

2017

Small molecule antagonists of the interaction between the histone deacetylase 6 zinc-finger domain and ubiquitin.

Harding 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: 29019676