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Steve Jackson

2017 Jackson

Steve Jackson PhD FRS FMedSci, Head of Institute's Cancer Research UK labs, Frederick James Quick Professor of Biology, Member of the Biochemistry Department. 

Jackson Group website | Europe PMC | Pubmed

Follow on Twitter @SPJacksonGroup 

 

 

Maintenance of genome stability

DNA is constantly damaged by environmental and endogenously arising agents. Cell survival and genome integrity are promoted by the DNA damage response (DDR), which detects, signals the presence of and repairs DNA damage. DDR defects are associated with developmental disorders, immunodeficiencies, infertility, premature ageing and cancer.

Our research aims to characterise the cell biology and mechanisms of established and new DDR pathways and components, and to apply this knowledge to better understand and treat human diseases.

Recently we have successfully used CRISPR-Cas9 synthetic viability screens to identify novel DDR proteins and define drug-resistance mechanisms. First, the novel protein complex Shieldin, that shields the ends of broken DNA and regulates DNA repair. Second, we have identified mechanisms in cells lacking the apical DDR kinase ATM that cause them to become resistant to certain anti-cancer drugs. These results are important for both understanding cancer drug resistance in the context of sporadic cancers and highlighting potential therapeutic targets for the genetic disease ataxia-telangiectasia.

Finally, our studies in a mouse model of Hutchinson-Gilford progeria syndrome (HGPS) showed that chemical or genetic inhibition of the enzyme NAT10 increased both the healthspan and lifespan of these mice. These findings suggest a therapeutic approach to HGPS and, potentially, other premature ageing diseases.

Selected publications:

• Balmus G et al. (2019) ATM orchestrates the DNA-damage response to counter toxic non-homologous end-joining at broken replication forks. Nat Commun. 10(1):87. doi: 10.1038/s41467-018-07729-2.

• Dev H et al. (2018) Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells. Nat Cell Biol. 20(8):954-965. doi:10.1038/s41556-018-0140-1.

• Balmus G et al. (2018) Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome. Nat Commun. 9(1):1700. doi: 10.1038/s41467-018-03770-3.

• Herzog M et al. (2018) Detection of functional protein domains by unbiased genome-wide forward genetic screening. Sci Rep. 8(1):6161. doi: 10.1038/s41598-018-24400-4.

• Blackford AN & Jackson SP. (2017) ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response. Mol Cell. 66(6):801-817. doi:10.1016/j.molcel.2017.05.015.

• Forment JV et al. (2017) Genome-wide genetic screening with chemically mutagenised haploid embryonic stem cells. Nat Chem Biol. 13(1):12-14. doi:10.1038/nchembio.2226.

Jackson group (Nov18 to Feb19)

Video: Meet Steve Jackson

Co-workers

Inigo Ayestaran • Linda Baskcomb • Rimma Belotserkovskaya • Ramsay Bowden • Julia Coates • Giuseppina D'Alessandro • Muku Demir • Harveer Dev • Kate Dry • Yaron Galanty • Maryam Ghaderi Najafabadi • Soren Hough • Rebecca Lloyd • Donna Lowe • David Morales • Francisco Muñoz Martinez • Dominic Pilger • Fabio Puddu • Elisenda Raga Gil • Helen Reed • Israel Salguero Corbacho • Matylda Sczaniecka-Clift • John Thomas •Guido Zagnoli-Vieira