Shane Harding

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Dr. Harding is a Scientist at the Princess Margaret Cancer Centre and Assistant Professor at the Department of Medical Biophysics at the University of Toronto. He received his Ph.D. in Medical Biophysics at the University of Toronto and completed his postdoctoral training at the University of Pennsylvania.

Genome stability, DNA damage and Cancer

Cells are faced with a barrage of stressors that cause damage to the DNA. This damage can drive mutations, changes in gene expression and development of diseases, most notably cancer. To counteract this damage and to maintain the integrity of the genome, multiple signalling pathways sense DNA lesions and facilitate their repair. Importantly, radiotherapy and many chemotherapeutics create large amounts of DNA damage that overwhelm these responses and cause cell death. One of the goals of the lab is to maximize these anti-cancer therapies through a better understanding of the DNA damage response.

More specifically, the lab is interested in how the DNA damage response interacts with ongoing cellular processes, including transcription. To this end we use biochemistry, molecular biology and genetic methods to elucidate how DNA damage responses cause changes in cellular physiology and genome organization that can manifest during cancer development and treatment. In particular, we focus on how radiotherapy can initiate cellular signalling paradigms that influence patient responses to immunotherapy. Through collaborative studies with clinical colleagues our aim is to translate work from our laboratory to improve the ability to eliminate tumours while reducing unwanted side-effects in patients.

Mol Biol Cell. 2018 Aug 08;29(16):1948-1962
Pfeifer CR, Xia Y, Zhu K, Liu D, Irianto J, García VMM, Millán LMS, Niese B, Harding S, Deviri D, Greenberg RA, Discher DE
Nature. 2017 08 24;548(7668):466-470
Harding SM, Benci JL, Irianto J, Discher DE, Minn AJ, Greenberg RA
Curr Biol. 2017 Jan 23;27(2):210-223
Irianto J, Xia Y, Pfeifer CR, Athirasala A, Ji J, Alvey C, Tewari M, Bennett RR, Harding SM, Liu AJ, Greenberg RA, Discher DE
Cell Rep. 2015 Oct 13;13(2):251-9
Harding SM, Boiarsky JA, Greenberg RA
Radiat Res. 2014 Nov;182(5):475-88
Cui L, Tse K, Zahedi P, Harding SM, Zafarana G, Jaffray DA, Bristow RG, Allen C
Oncogene. 2015 Apr 02;34(14):1780-9
El Ghamrasni S, Cardoso R, Halaby MJ, Zeegers D, Harding S, Kumareswaran R, Yavorska T, Chami N, Jurisicova A, Sanchez O, Hande MP, Bristow R, Hakem R, Hakem A
Mol Cell. 2014 Jan 09;53(1):7-18
Shibata A, Moiani D, Arvai AS, Perry J, Harding SM, Genois MM, Maity R, van Rossum-Fikkert S, Kertokalio A, Romoli F, Ismail A, Ismalaj E, Petricci E, Neale MJ, Bristow RG, Masson JY, Wyman C, Jeggo PA, Tainer JA
Int J Radiat Biol. 2011 Nov;87(11):1120-5
Mothersill C, Bristow RG, Harding SM, Smith RW, Mersov A, Seymour CB

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Assistant Professor, Department of Medical Biophysics, University of Toronto