Dr Daniel Rico Rodriguez
NU Research Fellow - Chromatin, Immunity and Bioinformatics
- Email: firstname.lastname@example.org
- Telephone: 01912087157
- Personal Website: https://blogs.ncl.ac.uk/danielrico/
- Address: Institute of Cellular Medicine
M2.123, William Leech Building
Computational biology approaches to study epigenomic regulation in immune cells
I am University Research Fellow at the Institute of Cellular Medicine in the University of Newcastle, UK. I lead a computational biology group focused in studying the gene regulatory programs and epigenomes of immune cells. More specifically, we want to understand the molecular mechanisms underlying the differences of the immune system in men and women.
Before joining Newcastle University, I have been deeply involved in the bioinformatics coordination two large-scale projects: the Spanish ICGC-CLL Genome Project, studying the genome, epigenome and transcriptome of chronic lymphocytic leukemia (Kulis et al, 2012, Ferreira et al, 2014, Ecker et al, 2015), and the Blueprint Consortium that has generated IHEC human reference epigenomes for most hematopoietic cell types and several leukemias (see IHEC papers). Moreover, I have led important methodological developments to dissect complex gene expression patterns from heterogeneous samples (Martinez-Garcia et al, 2014, Ecker et al, 2017), combining over hundred ChIP-seq experiments to reconstruct the first network of chromatin communication between proteins, histone marks and DNA modifications (Juan et al, 2016) and their relationship with the three-dimensional genome structure (Pancaldi et al, 2016). Finally, I have a long-standing interest in understanding how DNA replication and chromatin structure influence copy number variation and gene evolution (see our model in Juan, Rico et al, 2013).
Inmaculada Hernandez-Lopez, bioinformatician.
Maninder Heer, PhD student.
Sex-dependent gene regulation in immune cells
Despite the relevance of sexual dimorphism in both health and disease, there is still an important gap in our understanding of the role of sex in immune responses. The immune systems of men and women show remarkable differences, especially after puberty. For example, there is evidence showing significant differences in T-cell activation and proliferation, phagocytosis efficiency, cytokine production and response to vaccination. In general, reported differences include males being more exposed to infection risk than females, while in turn women show a higher risk of suffering autoimmune diseases but the biological mechanisms for these clinical-epidemiological observations remain unknown.
Any given cell’s developmental state and its future possible fates are believed to be determined by the epigenomic states of its chromatin. The epigenomic makeup of a cell not only conditions the genes that are switched on or off but also those (poised) genes that can be switched on under certain stimuli. In the context of autoimmunity, several studies have provided examples of epigenetic alterations that appear to be disease-associated and could offer a possible mechanism for the disproportionate sex ratios observed. However, most studies so far just focus on individual epigenetic features or particular genes and we need a more complete genome-wide picture of the molecular differences in immune cells in men and women.
A more complete genome-wide picture of the molecular differences in immune cells in men and women needs to be constructed to fully understand how the sex-encoded information of the genome influence their regulatory programmes. This genome-wide picture is challenging to construct because the high dimensionality of the epigenomic information, which it is dispersed in different un-connected databases and the need for new computational methods for analysis. Different data types must be processed, combined and interpreted.
We are developing integrative bioinformatics approaches to mine both publicly available data and new data generated by collaborators at Newcastle University. Focusing on the delineation of sex-dependent transcriptomic and epigenomic differences within the immune system, we are performing a systematic collection of the dispersed data and integrating the different layers in a common analytical framework. The ultimate goal of this effort is to connect the sex-specific gene expression programmes with the corresponding sex-specific chromatin configuration.
Wellcome Trust Seed Award in Science - ‘Sex-dependent gene regulation in immune cells’
I regularly offer computational biology research projects for Msc and MRes students at the Faculty of Medical Sciences.
- Rigau M, Juan D, Valencia A, Rico D. Widespread population variability of intron size in evolutionary old genes: implications for gene expression variability. BioRxiv 2017, Epub ahead of print.
- Pancaldi V, Carrillo-de-Santa-Pau E, Javierre BM, Juan D, Fraser P, Valencia A, Rico D. Integrating epigenomic data and 3D genomic structure with a new measure of chromatin assortativity. Genome Biology 2016, 17, 152.
- Carrillo-de-Santa-Pau E, Juan D, Pancaldi V, Were F, Martin-Subero I, Rico D, Valencia A, The BLUEPRINT Consortium. Automatic identification of informative regions with epigenomic changes associated to hematopoiesis. Nucleic Acids Research 2017, 45(16), 9244-9259.
- Ecker S, Chen L, Pancaldi V, Bagger FO, Fernandez JM, Carrillo-de-Santa-Pau E, Juan D, Mann AL, Watt S, Casale FP, Sidiropoulos N, Rapin N, Merkel A, BLUEPRINT Consortium, Stunnenberg HG, Stegle O, Frontini M, Downes K, Pastinen T, Kuijpers TW, Rico D, Valencia A, Beck B, Soranzo N, Paul DS. Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types. Genome Biology 2017, 18, 18.
- Juan D, Perner D, Carrillo de Santa Pau E, Marsili S, Ochoa D, Chung HR, Vingron M, Rico D, Valencia A. Epigenomic Co-localization and Co-evolution Reveal a key role for 5hmC as a Communication Hub in the Chromatin Network of ESCs. Cell Reports 2016, 14(5), 1246-1257.
- Stunnenberg HG, International-Human-Epigenome Consortium, Hirst M. The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery. Cell 2016, 167(5), 1145-1149.
- Fernández JM, de-la-Torre V, Richardson D, Royo R, Puiggròs M, Moncunill V, Fragkogianni S, Clarke L, BLUEPRINT Consortium, Flicek P, Rico D, Torrents D, Carrillo-de-Santa-Pau E, Valencia A. The BLUEPRINT Data Analysis Portal. Cell Systems 2016, 3(5), 491-495.e5.
- Chen L, Ge B, Casale FP, Vasquez L, Kwan T, Garrido-Martin D, Watt S, Yan Y, Kundu K, Ecker S, Datta A, Richardson D, Burden F, Mead D, Mann AL, Fernandez JM, Rowlston S, Wilder SP, Farrow S, Shao XJ, Lambourne JJ, Redensek A, Albers CA, Amstislavskiy V, Ashford S, Berentsen K, Bomba L, Bourque G, Bujold D, Busche S, Caron M, Chen SH, Cheung W, Delaneau O, Dermitzakis ET, Elding H, Colgiu I, Bagger FO, Flicek P, Habibi E, Iotchkova V, Janssen-Megens E, Kim B, Lehrach H, Lowy E, Mandoli A, Matarese F, Maurano MT, Morris JA, Pancaldi V, Pourfarzad F, Rehnstrom K, Rendon A, Risch T, Sharifi N, Simon MM, Sultan M, Valencia A, Walter K, Wang SY, Frontini M, Antonarakis SE, Clarke L, Yaspo ML, Beck S, Guigo R, Rico D, Martens JHA, Ouwehand WH, Kuijpers TW, Paul DS, Stunnenberg HG, Stegle O, Downes K, Pastinen T, Soranzo N. Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells. Cell 2016, 167(5), 1398-1414.
- Astle WJ, Elding H, Jiang T, Allen D, Ruklisa D, Mann AL, Mead D, Bouman H, Riveros-Mckay F, Kostadima MA, Lambourne JJ, Sivapalaratnam S, Downes K, Kundu K, Bomba L, Berentsen K, Bradley JR, Daugherty LC, Delaneau O, Freson K, Garner SF, Grassi L, Guerrero J, Haimel M, Janssen-Megens EM, Kaan A, Kamat M, Kim B, Mandoli A, Marchini J, Martens JH, Meacham S, Megy K, O'Connell J, Petersen R, Sharifi N, Sheard SM, Staley JR, Tuna S, van-der-Ent M, Walter K, Wang SY, Wheeler E, Wilder SP, Iotchkova V, Moore C, Sambrook J, Stunnenberg HG, Di-Angelantonio E, Kaptoge S, Kuijpers TW, Carrillo-de-Santa-Pau E, Juan D, Rico D, Valencia A, Chen L, Ge B, Vasquez L, Kwan T, Garrido-Martín D, Watt S, Yang Y, Guigo R, Beck S, Paul DS, Pastinen T, Bujold D, Bourque G, Frontini M, Danesh J, Roberts DJ, Ouwehand WH, Butterworth AS, Soranzo N. The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease. Cell 2016, 167(5), 1415-1429.e19.
- Esker S, Pancaldi V, Rico D, Valencia A. Higher gene expression variability in the more aggressive subtype of chronic lymphocytic leukemias. Genome Medicine 2015, 7(8).
- Kulis M, Merkel A, Heath S, Queirós AC, Schuyler RP, Castellano G, Beekman R, Raineri E, Esteve A, Clot G, Verdaguer-Dot N, Duran-Ferrer M, Russiñol N, Vilarrasa-Blasi R, Ecker S, Pancaldi V, Rico D, Agueda L, Blanc J, Richardson D, Clarke L, Datta A, Pascual M, Agirre X, Prosper F, Alignani D, Paiva B, Caron G, Fest T, Muench MO, Fomin ME, Lee ST, Wiemels JL, Valencia A, Gut M, Flicek P, Stunnenberg HG, Siebert R, Küppers R, Gut IG, Campo E, Martín-Subero JI. Whole-genome fingerprint of the DNA methylome during human B cell differentiation. Nature Genetics 2015, 47, 746-756.
- Martinez-Garcia M, Juan D, Rausell A, Muñoz M, Baños N, Menéndez C, López-Casas PP, Rico D, Valencia A, Hidalgo M. Transcriptional dissection of pancreatic tumors engrafted in mice. Genome Medicine 2014, 6, 27.
- Rico D, Juan D, Marques-Bonet T, Fernández-Capetillo O, Valencia A. Late-replicating CNVs as a source of new genes. Biology Open 2014, 3, 231-231.