Faculty of Biological Sciences

Dr Ron Chen

PhD, Imperial College London
University Academic Fellowship in Pervasive Transcription
School of Molecular and Cellular Biology

Background: Studied viral immunoevasion at Imperial College London in the Lab of Prof. Geoffrey Smith FRS. Subsequently worked with Prof. Julie Ahringer FMedSci on functional genomics at the Gurdon Institute, University of Cambridge. Appointed University Academic Fellow 2015.

Contact:  Garstang 8.52b, +44(0) 1133439608, email address for  

You can read more about Dr Chen's interests here:
Publications in PDFs:
www.researchgate.net/profile/Ron_Chen3
Lab webpage:
www.ronchenlab.info

Studying chromatin regulation in metazoan development to understand disease

We are interested in evolutionarily conserved biological processes in metazoan development. Our current research focuses on how chromatin regulation underlies the trans-differentiation steps, which would shed light on the pathogenesis process for the onset of human diseases including cancer. To address our big biological questions, we use the powerful genetic model organism C. elegans that share 70% of proteins encoded in the human genome. Most proteins involved in transcription and chromatin function are highly conserved. The comprehensive genetic tools (e.g. the genome-wide RNAi library), genomic information (e.g. modENCODE datasets), short life cycle (only 3 days), and the ease of molecular experiments (e.g. CRISPR genome editing) all make C. elegans a great experimental system to address basic biological questions at the organismal level. In parallel, we also use tissue-cultured mammalian cells to "translate" our worm work in order to aid the understanding of the underlying mechanism of human diseases.

 

CpG-islands: a HOT regulatory platform for epigenetic control 

CpG-rich promoters are frequently present across the C. elegans and human genome. Both worm and human CpG-rich coding promoters are highly accessible, marked by H3K4me3, and enriched for widely expressed active genes (Chen et al., 2013 Genome Research & Chen et al., 2014 Genome Research). The finding was highly surprising as CpG island promoters were only thought to have genomic significance in mammals. Currently, C. elegans is the only invertebrate genome showing mammalian CpG-island-like features. This makes C. elegans an attractive model to study conserved transcription regulation events, especially the function of H3K4me3 modifications and other histone modifications found in most active coding gene promoters enriched for CpGs. These widely active genomic regions have been found to harbour highly occupied target (HOT) regions for transcription factors in both C. elegans and humans (Chen et al., 2014 Genome Research). It suggests that CpG-dense promoters can function as regulatory hubs for chromatin regulators and consequently may modulate transcriptional activities.

CFP-1 is an evolutionarily conserved non-methylated CpG binding protein that binds to CpG-rich promoters in C. elegans (Chen et al., 2014 Genome Research), like in the mammalian genome. This conserved epigenetic regulator is part of the COMPASS complex that contains the major transferase for histone 3 lysine 4 tri-methylation (H3K4me3); SET-2 in C. elegans and Setd1A/B in mammals. H3K4me3 is frequently found in active promote regions, thus it has been used as an active promoter mark. The role of H3K4me3 in gene expression is unclear. To address this key question in epigenetic control, we are characterising cfp-1 and set-2 loss-of-function C. elegans mutants for their ability in inducing gene expression, specifying cell fate, and modulating chromatin architectures. 

 

Current Projects

(1) The interplay between chromatin modifiers/histone modifications in transdifferentiation in C. elegans germ cells, and murine myoblast /osteoblast cells    

(Collaborations with Prof. Mark Dickman, University of Sheffield, and Prof. Julie Ahringer, University of Cambridge) 

(2) The role of epigenetic control in the formation of oncogenic nucleic acid structures 

(Collaborations with Dr. Edwin Chen, University of Leeds, and Prof. Panagis Filippakopoulos, University fo Oxford) 

 

Faculty Research and Innovation



Studentship information

Undergraduate project topics:

  • Identifying novel genetic interactions between chromatin complexes in controlling cell fate specification and trans-generational epigenetic inheritance

Postgraduate studentship areas:

  • Identifying genetic regulators for oncogenic R-loops
  • Studying the contribution of COMPASS complex to epigenetic memory in C. elegans

See also:

Modules managed

BIOL2301 - Intermediate Skills for Biological Sciences
BIOL2303 - Intermediate Skills for Biotechnology
BIOL2305 - Integrated Skills for Biosciences 2

Modules taught

BIOC3160 - Laboratory/Literature/Computing Research Project
BIOC3900 - Cancer Biology
BIOL1303 - Introductory Skills for Biotechnology
BIOL2301/03/MICR2320 - Intermediate Skills - BIOL/MICR
BIOL5294M - MSc Bioscience Research Project Proposal
BIOL5382M - Extended Research Project
BIOL5392M - Bioscience MSc Research Project
BIOL5394M - Specialised Research Topics and Skills

Group Leader Dr Ron Chen  (University Academic Fellowship in Pervasive Transcription)

Postgraduates

Ghadah Alameer (Primary supervisor) 50% FTE
Yannic Chen (Primary supervisor) 90% FTE
Rosamund Clifford (Primary supervisor) 90% FTE
. Lalchungnunga (Primary supervisor) 40% FTE
Bharat Pokhrel (Primary supervisor) 90% FTE
Laura Warwick (Primary supervisor) 34% FTE
Benjamin Hopkins (Co-supervisor) 30% FTE
Dominic Lowen (Co-supervisor) 33% FTE
Dovile Milonaityte (Co-supervisor) 25% FTE

Ho JWK, Jung YL, Liu T, Alver BH, Lee S, Ikegami K, Sohn KA, Minoda A, Tolstorukov MY, Appert A, Parker SCJ, Gu T, Kundaje A, Riddle NC, Bishop E, Egelhofer TA, Hu SS, Alekseyenko AA, Rechtsteiner A, Asker D, Belsky JA, Bowman SK, Chen QB, Chen RAJ, Day DS, Dong Y, Dose AC, Duan X, Epstein CB, Ercan S, Feingold EA, Ferrari F, Garrigues JM, Gehlenborg N, Good PJ, Haseley P, He D, Herrmann M, Hoffman MM, Jeffers TE, Kharchenko PV, Kolasinska-Zwierz P, Kotwaliwale CV, Kumar N, Langley SA, Larschan EN, Latorre I, Libbrecht MW, Lin X, Park R, Pazin MJ, Pham HN, Plachetka A, Qin B, Schwartz YB, Shoresh N, Stempor P, Vielle A, Wang C, Whittle CM, Xue H, Kingston RE, Kim JH, Bernstein BE Comparative analysis of metazoan chromatin organization Nature 512 449-452, 2014
DOI:10.1038/nature13415
View abstract

Weick EM, Sarkies P, Silva N, Chen RA, Moss SMM, Cording AC, Ahringer J, Martinez-Perez E, Miska EA PRDE-1 is a nuclear factor essential for the biogenesis of Ruby motif-dependent piRNAs in C. elegans Genes and Development 28 783-796, 2014
DOI:10.1101/gad.238105.114
View abstract

Chen RAJ, Stempor P, Down TA, Zeiser E, Feuer SK, Ahringer J Extreme HOT regions are CpG-dense promoters in C. elegans and humans Genome Research 24 1138-1146, 2014
DOI:10.1101/gr.161992.113
View abstract

Chen RAJ, Down TA, Stempor P, Chen QB, Egelhofer TA, Hillier LDW, Jeffers TE, Ahringer J The landscape of RNA polymerase II transcription initiation in C. elegans reveals promoter and enhancer architectures Genome Research 23 1339-1347, 2013
DOI:10.1101/gr.153668.112
View abstract

Bahar MW, Graham SC, Chen RAJ, Cooray S, Smith GL, Stuart DI, Grimes JM How vaccinia virus has evolved to subvert the host immune response Journal of Structural Biology 175 127-134, 2011
DOI:10.1016/j.jsb.2011.03.010
View abstract

McCoy LE, Fahy AS, Chen RAJ, Smith GL Mutations in modified virus Ankara protein 183 render it a non-functional counterpart of B14, an inhibitor of nuclear factorκB activation Journal of General Virology 91 2216-2220, 2010
DOI:10.1099/vir.0.022343-0
View abstract

Graham SC, Bahar MW, Cooray S, Chen RAJ, Whalen DM, Abrescia NGA, Alderton D, Owens RJ, Stuart DI, Smith GL, Grimes JM Vaccinia virus proteins A52 and B14 share a Bcl-2-like fold but have evolved to inhibit Nf-κB rather than apoptosis PLoS Pathogens 4 -, 2008
DOI:10.1371/journal.ppat.1000128
View abstract

Chen RAJ, Ryzhakov G, Cooray S, Randow F, Smith GL Inhibition of IκB kinase by vaccinia virus virulence factor B14 PLoS Pathogens 4 -, 2008
DOI:10.1371/journal.ppat.0040022
View abstract

Cooray S, Bahar MW, Abrescia NGA, McVey CE, Bartlett NW, Chen RAJ, Stuart DI, Grimes JM, Smith GL Functional and structural studies of the vaccinia virus virulence factor N1 reveal a Bcl-2-like anti-apoptotic protein Journal of General Virology 88 1656-1666, 2007
DOI:10.1099/vir.0.82772-0
View abstract

Chen RAJ, Jacobs N, Smith GL Vaccinia virus strain Western Reserve protein B14 is an intracellular virulence factor Journal of General Virology 87 1451-1458, 2006
DOI:10.1099/vir.0.81736-0
View abstract

Jacobs N, Chen RAJ, Gubser C, Najarro P, Smith GL Intradermal immune response after infection with Vaccinia virus Journal of General Virology 87 1157-1161, 2006
DOI:10.1099/vir.0.81556-0
View abstract