Research Dr. Celia P. Martinez-Jimenez
Dr. Celia P. Martinez Jimenez has focused her scientific career on the mechanisms of gene regulation in diverse model organisms. During her PhD studies she developed differentiated human cell models as an alternative to animal work for drug screening and toxicity studies. She revealed a new distal enhancer module responsive to the regulation of the main cytochrome P450, CYP3A4, which metabolizes more than 60% of drugs currently in use (Martinez-Jimenez et al., Molecular Pharmacology 2005). Additionally, she discovered how a pivotal key liver-transcription factor (HNF4alpha) regulates and maintains the hepatic phenotype (Martinez-Jimenez et al., Journal of Biol Chemistry 2006; Martinez-Jimenez et al., Molecular Pharmacology 2006). She obtained her European PhD in 2006, and her graduate work lead to a distinguished National PhD Award by the University of Valencia (ES) (2007).
After her PhD, she moved to Greece, awarded by a highly competitive Marie Curie postdoctoral fellowship (ITN) to unravel the transcription factor network controlling hepatic fatty acid metabolism in vivo using different mouse models and dietary interventions (Martinez-Jimenez et al., Molecular & Cellular Biology 2010). In 2010, she returned to Spain to explore how posttranslational modifications regulate transcriptional complex dynamics in yeast (awarded with a prestigious FEBS long-term fellowship).
After her second postdoctoral stay, Dr. Martinez-Jimenez worked in a biotech company for three years (2012-2014). In January 2015, she re-engaged in science as the inaugural Janet Thornton Fellow (1) returning to research at the Wellcome Trust Sanger Institute and University of Cambridge (Cancer Research UK Cambridge Institute, UK). Since 2015, she has led single-cell genomic projects to explore the effect of aging on cell-to-cell transcriptional variability upon immune stimulation (Martinez-Jimenez et al. Science 2017). Dr. Martinez Jimenez discovered that aging leads to the disintegration of the immune response by increasing transcriptional heterogeneity within a conserve transcriptional program. Therefore, an increase in cell-to-cell transcriptional variability can be seen as a hallmark of aging.
In September 2018, Dr. Martinez Jimenez established her independent research group at the Helmholtz Pioneer Campus (HPC) in Munich (DE). At the HPC, she will investigate the molecular mechanisms of ageing focusing on the impact of cell-to-cell variation during healthy ageing and chronic diseases.
(1) The Janet Thornton Fellowship was launched in 2015 providing an opportunity specifically for those who have been out of scientific research for 12 months or more to return to high-quality postdoctoral training. http://www.sanger.ac.uk/about/sex-science
Single-cell genomic approaches have the power to reveal different sources of cellular variability (Fig.1). These technologies are allowing us to investigate the slow or subtle changes in cell type composition (cellular heterogeneity) or the changes in gene expression in homogenous populations of cells (transcriptional variability) which occur in chronic diseases and during healthy aging (Martinez-Jimenez et al. Science 2017).
Molecular features such as DNA methylation have recently been adopted as a predictor of “molecular age”. Dr. Martinez Jimenez has confirmed an additional feature predictive of molecular age: cell-to-cell transcription variability. Old mice have increased cell-to-cell transcriptional variability in their immune system in response to an external stimulus (Martinez-Jimenez et al. Science 2017). Although this increase in cell-to-cell transcriptional variability during aging has been reported in other cell types (Bahar R at al. Nature 2006), the impact of individual expression variability on tissue function has not yet been explored.
The Martinez-Jimenez Lab aims to compare “molecular age” (predicted by molecular features such as DNA methylation, chromatin accessibility and cell-to-cell transcriptional variability) with conventional “chronological age” (defined by the age of an individual in time units, years). These molecular features will be used to decipher the impact of cellular variability on tissue function during ageing and chronic disease.
The Martinez-Jimenez Lab integrates single-cell genomic approaches (transcriptomics, epigenomics and metabolomics) to study how ageing affects individual cells, different tissues and impact the health of the whole organism.
Martinez-Jimenez CP.* Eling N.*, Vallejos CA., Kolodziejczyk AA., Chen HC., Connor F., Stojic L., Rayner TF., Stubbington MJT., Teichmann SA., Roche M., Marioni JC., Odom DT. “Aging increases cell-to-cell transcriptional variability upon immune stimulation”. Science (2017).
Martinez-Jimenez C.P. and Odom D.T. “The mechanisms shaping the single-cell transcriptional landscape”. (Review) Current Opinion in Genetics & Development (2016) 27-35.
Schmidt D., Wilson M.D., Ballester B., Schwalie P.C., Gordon D. Brown G.D., Marshall A., Kutter C., Watt S., Martinez-Jimenez C.P., MacKay S., Enright A. J., Talianidis I., Flicek P, Odom D. T. “Five vertebrate ChIP-seq reveals the genetic mechanisms of rapid transcription factor binding divergence”. Science (2010).
Martinez-Jimenez CP., Kyrmizi I., Cardot P., Gonzalez FJ, Talianidis I. “HNF-4α coordinates the transcription factor network regulating hepatic fatty acid metabolism”. Mol. Cell Biology (2010).
Martinez-Jimenez, C.P., Castell, J.V., Gómez-Lechón, M.J., Jover, R. “Transcriptional activation of CYP2C9, CYP1A1 and CYP1A2 by HNF4α requires coactivators PGC1α and SRC1”. Molecular Pharmacology (2006).
Martinez-Jimenez CP., Gómez-Lechón, MJ., Castell, JV., Jover, R. “Transcriptional regulation of the human hepatic CYP3A4: Identification of a new distal enhancer module in the human hepatic CYP3A4 responsive to CCAAT/enhancer binding protein beta isoforms (LAP and LIP)”. Molecular Pharmacology (2005).
Join the Team
Highly motivated individuals are encouraged to apply to available and fully funded positions on all the levels (research assistant, PhD student and postdoc positions). Personal development plans will be studied for each candidate individually to tailor their training and acquisition of competences during the stay in the lab.