Rachel Harding

Rachel Harding

SGC Toronto

Harding

Biography

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.

Research Areas

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.

2026

CACHE Challenge #3: Targeting the Nsp3 Macrodomain of SARS-CoV-2.

Herasymenko O, Silva M, Correy GJ, Abu-Saleh AAA, Ackloo S, Arrowsmith C, Ashworth A, Ban F, Beck H, Bishop KP, Bohórquez HJ, Bolotokova A, Breznik M, Chau I, Chen Y, Cherkasov A, Dehaen W, Della Corte D, Denzinger K, Doering NP, Edfeldt K, Edwards A, Fayne D, Gentile F, Gibson E, Gokdemir O, Gunnarsson A, Günther J, Irwin JJ, Jensen JH, Harding RJ, Hillisch A, Hoffer L, Hogner A, Hutchinson A, Kandwal S, Karlova A, Koirala K, Kotelnikov S, Kozakov D, Lee J, Lee S, Lessel U, Liu S, Liu X, Loppnau P, Meiler J, Moretti R, Moroz YS, Muvva C, Oprea TI, Paige B, Pandit A, Park K, Poda G, Protopopov MV, Pütter V, Ravichandran R, Rognan D, Rosta E, Sabnis Y, Scott T, Seitova A, Sharma P, Sindt F, Song M, Steinmann C, Stevens R, Talagayev V, Tararina VV, Tarkhanova O, Tingey D, Trant JF, Treleaven D, Tropsha A, Walters P, Wells J, Westermaier Y, Wolber G, Wortmann L, Zheng S, Fraser JS, Schapira M

J Chem Inf Model. 2026-1-22 . .doi: 10.1021/acs.jcim.5c02441

PMID: 41565251

2025

Enantioselective protein affinity selection mass spectrometry (E-ASMS).

Wang X, Sun J, Ahmad S, Yang D, Li F, Chan UH, Zeng H, Simoben CV, Green SR, Silva M, Houliston S, Dong A, Bolotokova A, Gibson E, Kutera M, Ghiabi P, Kondratov I, Matviyuk T, Chuprina A, Mavridi D, Lenz C, Joerger AC, Brown BD, Heath RB, Yue WW, Robbie LK, Beyett TS, Müller S, Knapp S, Owen DR, Harding R, Schapira M, Brown PJ, Santhakumar V, Ackloo S, Arrowsmith CH, Edwards AM, Peng H, Halabelian L

Nat Commun. 2025-12-18 . .doi: 10.1038/s41467-025-67403-2

PMID: 41407727

Enabling Open Machine Learning of Deoxyribonucleic Acid-Encoded Library Selections to Accelerate the Discovery of Small Molecule Protein Binders.

Wellnitz J, Ahmad S, Bagale N, Cheng X, Joseph J, Zeng H, Bolotokova A, Dong A, Reza S, Ghiabi P, Gibson E, Tu G, Li X, Liu J, Dou D, Li J, Foley TL, Harris AR, Klug-McLeod JL, Lee J, Lengyel-Zhand Z, Montgomery JI, Sakata S, Zhang J, Zhu H, Owen DR, Harding RJ, Edwards AM, Haibe-Kains B, Halabelian L, Tropsha A, Couñago RM

J Med Chem. 2025-10-6 . .doi: 10.1021/acs.jmedchem.5c01972

PMID: 41047897

CACHE Challenge #2: Targeting the RNA Site of the SARS-CoV-2 Helicase Nsp13.

Herasymenko O, Silva M, Abu-Saleh AAA, Ahmad A, Alvarado-Huayhuaz J, Arce OEA, Armstrong RJ, Arrowsmith C, Bachta KE, Beck H, Berta D, Bieniek MK, Blay V, Bolotokova A, Bourne PE, Breznik M, Brown PJ, Campbell ADG, Carosati E, Chau I, Cole DJ, Cree B, Dehaen W, Denzinger K, Dos Santos Machado K, Dunn I, Durai P, Edfeldt K, Edwards A, Fayne D, Felfoldi D, Friston K, Ghiabi P, Gibson E, Günther J, Gunnarsson A, Hillisch A, Houston DR, Jensen JH, Harding RJ, Harris KS, Hoffer L, Hogner A, Horton JT, Houliston S, Hultquist JF, Hutchinson A, Irwin JJ, Jukič M, Kandwal S, Karlova A, Katis VL, Kich RP, Kireev D, Koes D, Inniss NL, Lessel U, Liu S, Loppnau P, Lu W, Martino S, McGibbon M, Meiler J, Mettu A, Money-Kyrle S, Moretti R, Moroz YS, Muvva C, Newman JA, Obendorf L, Paige B, Pandit A, Park K, Perveen S, Pirie R, Poda G, Protopopov M, Pütter V, Ricci F, Roper NJ, Rosta E, Rzhetskaya M, Sabnis Y, Satchell KJF, Schmitt Kremer F, Scott T, Seitova A, Steinmann C, Talagayev V, Tarkhanova OO, Tatum NJ, Treleaven D, Velasque Werhli A, Walters WP, Wang X, Wells J, Wells G, Westermaier Y, Wolber G, Wortmann L, Zhang J, Zhao Z, Zheng S, Schapira M

J Chem Inf Model. 2025-6-20 . .doi: 10.1021/acs.jcim.5c00535

PMID: 40539604

Active Learning-Guided Hit Optimization for the Leucine-Rich Repeat Kinase 2 WDR Domain Based on In Silico Ligand-Binding Affinities.

Gusev F, Gutkin E, Gentile F, Ban F, Koby SB, Li F, Chau I, Ackloo S, Arrowsmith CH, Bolotokova A, Ghiabi P, Gibson E, Halabelian L, Houliston S, Harding RJ, Hutchinson A, Loppnau P, Perveen S, Seitova A, Zeng H, Schapira M, Cherkasov A, Isayev O, Kurnikova MG

J Chem Inf Model. 2025-5-26 . .doi: 10.1021/acs.jcim.5c00588

PMID: 40415386

PRMT5 promotes full-length HTT expression by repressing multiple proximal intronic polyadenylation sites.

Yadav M, AlQazzaz MA, Ciamponi FE, Ho JC, Maron MI, Sababi AM, MacLeod G, Ahmadi M, Bullivant G, Tano V, Langley SR, Sánchez-Osuna M, Sachamitr P, Kushida M, Bardile CF, Pouladi MA, Kurtz R, Richards L, Pugh T, Tyers M, Angers S, Dirks PB, Bader GD, Truant R, Massirer KB, Barsyte-Lovejoy D, Shechter D, Harding RJ, Arrowsmith CH, Prinos P

Nucleic Acids Res. 2025-4-30 . 53(8): .doi: 10.1093/nar/gkaf347

PMID: 40304179

Challenges and advances for huntingtin detection in cerebrospinal fluid: in support of relative quantification.

Harding RJ, Xie Y, Caron NS, Findlay-Black H, Lyu C, Potluri N, Chandrasekaran R, Hayden MR, Leavitt BR, Langbehn DR, Southwell AL

Biomark Res. 2025-4-22 . 13(1):63 .doi: 10.1186/s40364-025-00772-4

PMID: 40259428

Revisiting huntingtin activity and localization signals in the context of protein structure.

Truant R, Harding RJ, Neuman K, Maiuri T

J Huntingtons Dis. 2025-2-20 . 13(4):419-430 .doi: 10.1177/18796397241295303

PMID: 39973382

Enantioselective Protein Affinity Selection Mass Spectrometry (EAS-MS).

Wang X, Sun J, Ahmad S, Yang D, Li F, Chan UH, Zeng H, Simoben CV, Houliston S, Dong A, Bolotokova A, Gibson E, Kutera M, Ghiabi P, Kondratov I, Matviyuk T, Chuprina A, Mavridi D, Lenz C, Joerger AC, Brown BD, Heath RB, Yue WW, Robbie LK, Beyett TS, Müller S, Knapp S, Harding R, Schapira M, Brown PJ, Santhakumar V, Ackloo S, Arrowsmith CH, Edwards AM, Peng H, Halabelian L

bioRxiv. 2025-2-3 . .doi: 10.1101/2025.01.17.633682

PMID: 39896675

Functionally active modulators targeting the LRRK2 WD40 repeat domain identified by FRASE-bot in CACHE Challenge #1.

Mettu A, Glavatskikh M, Wang X, Lara Ordóñez AJ, Li F, Chau I, Ackloo S, Arrowsmith C, Bolotokova A, Ghiabi P, Gibson E, Halabelian L, Houliston S, Harding RJ, Hutchinson A, Loppnau P, Perveen S, Seitova A, Zeng H, Schapira M, Taymans JM, Kireev D

Chem Sci. 2025-1-29 . .doi: 10.1039/d4sc07532c

PMID: 39877816