Adam Woolfe's Homepage

I am currently a bioinformatics post-doctoral fellow at the Institut Curie in Paris, France in the lab of Dr Genevieve Almouzni and Emmanuel Barillot.

Previously, I was a post-doc in the Genome Technology Branch of the National Human Genome Research Institute, in the lab of Dr Laura Elnitski.

My current research interests include:

Study of histone variants and epigenetics
Study of epigenetic changes in breast cancer using second-generation sequencing approaches.
Evolution of histone chaperones
DNA structure-based encoding of nucleosome positioning

You can email me at adam.woolfe [at] curie.fr

TOOLS AND DATABASES

I part of my PhD i developed the database of COnserved Non-coDing Orthologous Regions (CONDOR) which holds data on conserved non-coding elements identified through fish-mammal alignments and in-vivo enhancer assays. The database also highlights elements that derive from both vertebrate whole-genome duplications events and teleost specific duplications that may have played a role in speciation and regulatory divergence.
I have also developed a webtool, Skippy, to score genomic variants for features associated with exon skipping and ectopic splice site creation. With large numbers of novel variants being identified by next-gen sequencing projects, this tool should help identify novel cases of disease associated variants that affect splicing.

PUBLICATIONS

Ray-Gallet D, Woolfe A, Vassias I, Pellentz C, Lacoste N, Puri A, Schultz DC, Pchelintsev NA, Adams PD, Jansen LE, Almouzni G. (2011) Dynamics of histone H3 deposition in vivo reveal a nucleosome gap-filling mechanism for H3.3 to maintain chromatin integrity. Molecular Cell.44:928-941 [LINK]

Woolfe A, Mullikin JC and Elnitski L. (2010) Genomic features defining exonic variants that modulate splicing. Genome Biology.11:R20 [PDF]

McEwen G, Goode DK,Parker HJ,Woolfe A,Callaway H and Elgar G. (2009) Early evolution of conserved regulatory sequences associated with development in vertebrates. PLoS Genetics.5:e1000762 [PDF]

Woolfe A, Goode D, Cooke J, Callaway H, Smith S, Snell P, McEwen G and Elgar G. (2007) CONDOR: a database resource of developmentally-associated conserved non-coding elements. BMC Developmental Biology.7:100 [PDF]

Woolfe A and Elgar G. (2007) Comparative genomics using Fugu reveals insights in regulatory subfunctionalization. Genome Biol.8:R53 [PDF]

McEwen GK, Woolfe A, Goode G, Vavouri T, Callaway H and Elgar G. (2006) Ancient duplicated conserved noncoding elements in vertebrates: a genomic and functional analysis. Genome Res.16: 5-10 [PDF]

Vavouri T, McEwen GK, Woolfe A, Gilks WR and Elgar G. (2006) Defining a genomic radius for long-range enhancer action: duplicated conserved non-coding elements hold the key. Trends Genet.22: 5-10 [Link]

Woolfe A, Goodson M, Goode DK, Snell P, McEwen GK, Vavouri T, Smith SF, North P, Callaway H, Kelly K, Walter K, Abnizova I, Gilks W, Edwards YJ, Cooke JE, Elgar G. (2005). Highly Conserved Non-Coding Sequences Are Associated with Vertebrate Development. PLoS Biol. 2005 Jan; 3(1): e7 [PDF]

BOOK CHAPTERS

Woolfe A and Elgar G. Chapter 12 - Organization of Conserved Elements Near Key Developmental Regulators in Vertebrate Genomes. Long Range Control of Gene Expression. Advances in Genetics. 2008. Elsevier Publications. [Link]

CONFERENCE PRESENTATIONS AND POSTERS

Woolfe A, Ray-Gallet D and Almouzni G (May 2011). Histone variant H3.3, RNA Pol II, the histone chaperone HIRA at mammalian transcribed genes and cis-regulatory elements. Poster presentation at the Biology of Genomes meeting at CSHL, New York.

Woolfe A, Parmigiani G, Mullikin J and Elnitski L (July 2008). Prediction of novel intra-exonic mutations that affect splicing. Poster presentation at the GORDON conference The Biology of Post-Transcriptional Gene Regulation at Colby College, Maine.

Woolfe A and Elgar G (November 2004). CONDOR: creation of an annotated database of vertebrate developmentally-associated conserved non-coding sequences. Poster presentation at the genomics workshop Identification of Functional Elements in Mammalian Genomes at CSHL, New York.

Woolfe A, Cooke J, Goode G, Snell P and Elgar G (August, 2004). Using fish phylogenetic footprinting to identify vertebrate specific regulatory regions. Poster presentation at ISMB/ECCB, Glasgow, Scotland.

Woolfe A and Elgar G (March, 2004). Using fish phylogenetic footprinting to identify vertebrate specific regulatory regions. Oral presentation at the meeting Systems Biology: Genomic Approaches to Transcriptional Regulation at CSHL, New York.

EDUCATION AND QUALIFICATIONS:

2002-2006     University of Cambridge/MRC RFCGR/Wellcome Trust Sanger Institute
                            PhD Comparitive Genomics/Bioinformatics
                            Thesis: "Computational detection and analysis of putative cis-regulatory elements in vertebrate genomes".

2000-2001     University of Manchester
                            MSc Bioinformatics
                            Industry Bioinformatics placement at British Biotech (now Vernalis), Oxford.

1996-2000     University of Manchester
                            BSc (Hons) Molecular Biology with a Year in Industry
                            Year in industry: a 10 month placement at the Dept. of Molecular Genetics and Biotechnology, Hadassah Medical School, Jerusalem, Israel.

PhD THESIS SUMMARY

Study of the regulatory architecture of vertebrate genomes is providing one of the biggest challenges of the post-genomic era. Fish-mammal genomic comparisons have proved powerful in identifying conserved non-coding elements likely to be distal cis-regulatory modules such as enhancers, silencers or insulators. In addition, there is increasing evidence that such elements are strongly associated with genes involved in transcriptional regulation and development. Here, by using a targeted multiple-alignment strategy of orthologous genomic sequence from the Japanese pufferfish Fugu rubripes together with that of a number of mammals, I identified a large set of conserved non-coding elements (CNEs) surrounding more than 100 regulator genes involved in early development. To facilitate a further in-depth analysis of these elements for this study and public use, a relational database CONDOR (database of COnserved NoncoDing Orthologous Regions) and front-end were designed to store and access this data together with associated functional data issuing from wet-lab experimentation. The database can be accessed at condor.nimr.mrc.ac.uk.

Using the database, I studied a number of evolutionary and sequence-based aspects of these intriguing elements and found they are distinct in many ways from other functional sequences such as coding exons. In addition, a small proportion of these elements show sequence similarity to other parts of the genome and appear to be associated with nearby paralogous genes that date back to the large-scale duplication events at the origin of vertebrates. Finally I carried out a comparative analysis of CNEs identified around seven pairs of Fugu developmental genes that derive from whole-genome duplication early in the teleost lineage. Presence of shared and distinct CNEs between duplicated genes suggest they are likely to have undergone a process of regulatory subfunctionalisation the extent of which differs between duplicate pairs.