PROJECT
SUPERVISORS
Project Supervisor
Manel Esteller
Background
I graduated in Medicine from the University of Barcelona in 1992, where I also obtained my PhD degree specialising in molecular genetics of endometrial carcinoma, in 1996. I was an Invited Researcher at the School of Biological and Medical Sciences at the University of St. Andrews (Scotland, UK) during which time my research interests focused on the molecular genetics of inherited breast cancer. From 1997 to 2001, I was a Postdoctoral Fellow and a Research Associate at the Johns Hopkins University and School of Medicine, (Baltimore, USA) where I studied DNA methylation and human cancer. My work was decisive in establishing promoter hypermethylation of tumour suppressor genes as a common hallmark of all human tumours.
From October 2001 to September 2008 I established the Cancer Epigenetics Laboratory at the CNIO, where my principal areas of research were alterations in DNA methylation, histone modifications and chromatin in human cancer. I continued my research in this field as the Director of the Cancer Epigenetics and Biology Program (PEBC) in the Bellvitge Biomedical Campus of Barcelona for ten years.
From May 2019, I am the Director of the Josep Carreras Leukaemia Research Institute (IJC) and I’m also Chairman of Genetics at the School of Medicine of the University of Barcelona, and an ICREA Research Professor. My current research is devoted to the establishment of the epigenome and epitranscriptome maps for normal and transformed cells, the study of the interactions between epigenetic modifications and non-coding RNAs, and the development of new epigenetic drugs for cancer therapy.
Research
Malignant cells behave differently than the rest of the tissue, displaying capacities reserved for stem cells, like proliferation. Since all cells in an organism share the same genetic information, the difference between any cell type, malignant cells included, is the subset of the information they have access to. The term epigenetics refers to the many control layers limiting a cell’s accessibility to only those parts of the genome relevant to its organic function.
Our group aims at understanding the fundamental epigenetic and epitranscriptomic mechanisms acting in living cells, like DNA methylation and histone modification patterns, or gene expression regulation through microRNAs. These mechanisms do not affect the very cell’s genetic information, only its availability to be used, and its alteration may be the beginning of an abnormal behaviour. Malfunction of the epigenetic control is among the less understood causes of human tumours and its knowledge is key to develop new strategies against tumour formation and cancer.
Publications
Janin M et al. Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program. Acta Neuropathol. 2019
Bueno-Costa A et al. B-cell leukemia transdifferentiation to macrophage involves reconfiguration of DNA methylation for long-range regulation. Leukemia. 2019
Rosselló-Tortella M et al. Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer. Proc Natl Acad Sci U S A. 2020
Esteve-Puig R et al. Epigenetic Loss of m1A RNA Demethylase ALKBH3 in Hodgkin Lymphoma Targets Collagen Conferring Poor Clinical Outcome. Blood. 2020
Wheeler DA et al. Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment. Cancer Cell . 2020