Dr Spencer J Collis
CRUK Senior Cancer Research Fellow
Institute for Cancer Studies,
Department of Oncology,
The University of Sheffield Medical School,
Beech Hill Road,
Sheffield S10 2RX
Telephone: +44 (0)114 271 1543
Facsimilie: +44 (0)114 271 1602
1994 - 1997
BSc (Hons): Biochemistry, UMIST
1997 - 2000
PhD: Oncology, CRUK Paterson Institute for Cancer Research
2001 - 2004
Prof. Theodore DeWeese laboratory, Johns Hopkins University
2004 - 2009
Dr. Simon Boulton laboratory, CRUK London Research Institute, Clare Hall Laboratories
YCR Institute for Cancer Studies, University of Sheffield
Cellular responses to DNA damage involve the orchestration of cell cycle checkpoints and DNA repair factors, which are rapidly activated and mobilised to sites of DNA damage. Defects in checkpoint and DNA repair factors are causal for several genetically unstable human disorders that predispose to cancer. A detailed molecular understanding of these pathways will expand our knowledge of cancer development and progression, which may lead to novel or improved treatments
We have recently identified and partially characterised HCLK2 as a novel factor required for the cellular response to DNA damage (Collis et al 2007). Through proteomic and yeast two-hybrid approaches we have now discovered a number of novel HCLK2-interacting proteins (CIPs; Collis et al 2008) which we are characterising further using a combination of proteomics, loss of function (RNAi), sub-cellular localisation, and biochemical studies to determine their role in DNA damage response pathways. Encouragingly, our preliminary studies have shown that cells depleted for several CIPs confer defects in DNA damage signalling.
In addition, we have recently completed a human genome-wide RNAi screen to identify novel genome maintenance factors (GMFs). A high proportion of known DNA replication and DNA damage/checkpoint factors were identified in the primary screen, in addition to a number of new GMFs. Secondary screens are now underway to refine the list of candidates, which will then be depleted individually in cells using RNAi treatments and subjected to various assays to determine their roles in DNA damage signalling and/or repair. Preliminary studies using 4 individual RNAi`s against two novel GMFs have confirmed evidence of genome instability and defective DNA damage signalling in these cells.
Based on these and future experiments, we will also investigate if mutations in any CIPs or GMFs are causal for cancer and genetically unstable human disorders, as well as defining their potential as putative anti-cancer drug targets.
M.Sc. Molecular Medicine
M.Sc. Translational Oncology (from 2013)
Staples CJ, Myers KN, Beveridge RD, Patil AA, Lee AJ, Swanton C, Howell M, Boulton SJ & Collis SJ.
The centriolar satellite protein Cep131 is important for genome stability.
J Cell Sci. Advance Online Publication July 13, 2012, doi:10.1242/jcs.104059
Adamo A*, Collis SJ*, Adelman CA, Silva N, Ward JD, Martinez-Perez E, Boulton SJ & La Volpe A. *co-first authorship
Preventing Non-Homologous End Joining Suppresses DNA repair defects of Fanconi Anemia.
Molecular Cell 39(1), 25-35 2010.
Collis SJ, Ciccia A, Deans AJ, Hořejší Z, Martin JS, Maslen SL, Skehel JM, Elledge SJ, West SJ & Boulton SJ.
FANCM and FAAP24 function in ATR-mediated checkpoint signalling independent of the Fanconi Anemia core complex
Molecular Cell 32(3), 313-324, 2008
Collis SJ, Barber LJ, Clark, AJ, Martin JS, Ward, JD and Boulton SJ.
HCLK2 is essential for the mammalian S-phase checkpoint and impacts on Chk1 stability
Nature Cell Biology 9(4), 391-401, 2007.