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Dheva Setiaputra
Areas of interest
Maintaining genome stability is a challenge that every form of life must address. It is a fundamental biochemical process that plays a critical role in both disease development and therapy. For example, improper repair of DNA damage induces mutations that give rise to cancer. However, the inherent DNA repair deficiency of cancerous cells can be exploited by genotoxic therapy that results in specific cell death. Furthermore, with the advent of CRISPR-based therapeutics, the cellular response to Cas9-induced DNA breaks has resounding effects in clinical outcomes. It is essential to understand the molecular pathways that facilitate DNA repair to exploit it for cancer and gene therapy.
In the Setiaputra lab, we focus on exploring the molecular mechanisms underlying DNA repair pathway choice. There are multiple potential pathways that respond to DNA damage, and which pathway is brought to bear carries profound implications in the toxicity and mutational outcomes caused by specific genotoxic insults. The molecular basis of the cellular decisions leading to a specific repair trajectory is poorly understood. We use mammalian cell culture combined with biochemistry, cell biology, genomics, and computational biology to address this gap in understanding. Our ultimate goal is to leverage fundamental DNA repair research to identify novel targets and paradigms in targeted cancer therapy and gene editing.
Education
- BSc Honours., Biochemistry and Molecular Biology, University of British Columbia
- PhD, Biochemistry and Molecular Biology, University of British Columbia
- Postdoctoral fellow, Lunenfeld_Tanenbaum Research Institute
Selected Publication
- An AlphaFold2 map of the 53BP1 pathway identifies a direct SHLD3–RIF1 interaction critical for shieldin activity. Sifri C, Hoeg L, Durocher D, Setiaputra D. EMBO Reports (2023). doi:10.17632/dj2kv8zzxy.
- RIF1 acts in DNA repair through phosphopeptide recognition of 53BP1. Setiaputra D, Escribano-Diaz C, Reinert JK, Sadana P, Zong D, Callen E, Sifri C, Seebacher J, Nussenzweig A, Thomä NH, Durocher D. Molecular Cell (2022). doi:10.1016/j.molcel.2022.01.025.
- Shieldin—the protector of DNA ends. Setiaputra D, Durocher D. EMBO Reports (2019). doi:10.15252/embr.201847560.
- The shieldin complex mediates 53BP1-dependent DNA repair. Noordermeer SM, Adam A*, Setiaputra D*, Barazas M, Pettitt SJ, Ling AK, Olivieri M, Álvarez-Quilón A, Moatti N, Zimmermann M, Annunziato S, Krastev DB, Song F, Brandsma I, Frankum J, Brough R, Sherker A, Landry S, Szilard RK, Munro MM, McEwan A, Goullet de Rugy T, Lin ZY, Hart T, Moffat J, Gingras AC, Martin A, van Attikum H, Jonkers J, Lord CJ, Rottenberg S, Durocher D. Nature (2018). doi:10.1038/s41586-018-0340-7. *Co-first authors.