Dr Spencer J Collis

Reader in Genome StabilitySpencer Collis new

Academic Unit of Molecular Oncology
Head of the Genome Stability Group
Department of Oncology & Metabolism
The University of Sheffield Medical School
Beech Hill Road
Sheffield S10 2RX
United Kingdom

Telephone: +44 (0)114 215 9043
Email:
s.collis@sheffield.ac.uk

Biography

1994 - 1997
BSc (Hons): Biochemistry, UMIST

1997 - 2000
PhD: Oncology, CRUK Paterson Institute for Cancer Research

2001 - 2004
Post-Doc: Prof. Theodore DeWeese laboratory, Johns Hopkins University

2004 - 2009
Post-Doc: Dr. Simon Boulton laboratory, Clare Hall Laboratories, CRUK London Research Institute

2009 - 2013
Group leader: Institute for Cancer Studies, University of Sheffield

2013 - 2015
Senior Lecturer: Academic unit of Molecular Oncology, Department of Oncology, University of Sheffield

2016 -
Reader:  Academic unit of Molecular Oncology, Department of Oncology, University of Sheffield

Research interests

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 are investigating 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.

Teaching Interests

M.Sc. Molecular Medicine
M.Sc. Translational Oncology
MSc Genomic Medicine

Key publications

Barone G, Arora A, Ganesh A, Abdel-Fatah T, Moseley P, Ali R, Chan SYT, Savva C, Schiavone C, Carmell N, Myers KN, Rakha E, Madhusudan S & Collis SJ.  The relationship of CDK18 expression in breast cancer to clinicopathological parameters and therapeutic response.  Oncotarget: 9(50) 29508-29524, 2018.

Myers KN, Barone G, Staples CJ, Howard AE, Beveridge RD, Maslen S, Skehel JM & Collis SJ. The bornavirus-derived human protein EBLN1 promotes efficient cell cycle transit, microtubule organisation and genome stability. Scientific Reports: 6(35548), 2016.

Staples CJ, Barone G, Myers KN, Ganesh A, Gibbs-Seymour I, Patil AA, Beveridge RD, Daye C, Beniston R, Maslen S, Ahel A, Skehel, JM & Collis SJ. MRNIP/C5orf45 interacts with the MRN complex and contributes to the DNA damage response. Cell Reports: 16(10), 2565-2575, 2016.

Barone G, Staples CJ, Myers KN, Paterson KW, McKenzie EA, Eyers CE, Maslen S, Skehel, JM, Eyers PA* & Collis SJ*.  CDK18 promotes replication stress signalling and genome stability.  Nucleic Acids Research: 44(18), 8772-8785, 2016. *Co-corresponding authors.

Johnson CA* & Collis SJ*.  Ciliogenesis and the DNA damage response; a stressful relationship..
Cilia; 5(19), 2016. *co-corresponding authors 

Beveridge RD, Staples CJ, Patil AA, Myers KN, Maslen S, Skehel JM, Boulton SJ & Collis SJ.
The leukaemia-associated Rho guanine nucleotide exchange factor LARG is required for efficient replication stress signalling. Cell Cycle 13(21), 3450-3459, 2014.

Patil AA, Sayal P, Depondt ML, Beveridge RD, Roylance A, Krinlani DH, Myers K, Cox A, Jelinek D, Fernando M, Carroll TA & Collis SJ.  FANCD2 re-expression is associated with glioma grade and chemical inhibition of the Fanconi Amaemia pathway sensitises gliomas to chemotherapeutic agents.  Oncotarget 5(15) 6414-6424, 2014. 

Staples CJ, Myers KN, Beveridge RD, Patil AA, Howard AE, Barone G, Lee AJX, Swanton C, Howell M, Maslen S, Skehel JM, Boulton SJ & Collis SJ.  Ccdc13; a novel human centriolar satellite protein required for ciliogenesis and genome stability.  J Cell Sci. 127(13), 2910-2919, 2014.

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. 125(20), 4770-4779, 2012.

For a full list of publications please visit myPublications

Collis Lab