PROJECT
SUPERVISORS
Project Supervisor
José Luis Sardina
Background
I earned my Bachelor's degrees in Biology and Biochemistry from the University of Salamanca (Spain) in 2005 and 2006 respectively. I also received my Ph.D. in Biology from the same university in 2010. During my Ph.D., I researched the role of reactive oxygen species (ROS) and protein tyrosine phosphatases in hematopoietic differentiation under the supervision of Dr. Ángel Hernández Hernández and Dr. Jesús Sánchez Yagüe.
After obtaining my Ph.D., I worked as a postdoc at the Institute of Functional Biology and Genomics (IBFG, Salamanca) under the guidance of Prof. Francisco Antequera, where I researched aberrant CpG island methylation under conditions of cellular stress and cancer. In 2012, I joined the laboratory of Prof. Thomas Graf (CRG, Barcelona) for a second postdoctoral stage as a Juan de la Cierva Fellow. During this time, I focused on developing new protocols for efficient and ultrafast conversion of mouse and human pre-B lymphocytes into induced pluripotent stem cells (iPSCs). Later, I discovered the molecular mechanisms underlying cell fate conversion involving the Tet2 DNA dioxygenase in the process. In Fall 2019, I joined the Josep Carreras Leukaemia Research Institute (IJC) as a Miguel Servet researcher to lead the Epigenetic Control of Haematopoiesis group. My team is focused on understanding how aberrant DNA methylation at distal gene regulatory regions poisons the chromatin to trigger corrupted gene expression signatures in the cells, ultimately leading to disease onset and progression.
Research
Our group is dedicated to exploring the intricate molecular mechanisms that govern cellular fates within the hematopoietic system. Our focus lies on investigating those mechanisms that lead to immune system malfunctions. By employing cutting-edge techniques like RNA-seq, WG(ox)BS-seq, ATAC-seq, and ChIP-seq for histone marks, we are able to delve deeper into the role of chromatin regulation in determining immune cellular fates.
In addition, we are utilizing CRISPR/Cas9 epigenome editing tools on innovative cellular models to conduct in-depth molecular studies. Our primary objective is to dissect the fundamental connections between epigenomic changes, gene expression, and the onset of immune diseases. Our research has the potential to inspire groundbreaking new treatments for immune system disorders.
Publications
Vitamin C enhances NF-κB-driven epigenomic reprogramming and boosts the immunogenic properties of dendritic cells. Morante-Palacios O, Godoy-Tena G, Calafell-Segura J, Ciudad L, Martínez-Cáceres EM, Sardina JL, Ballestar E$. Nucleic Acids Res. 2022 Oct 28;50(19):10981-10994. doi: 10.1093/nar/gkac941. PMID: 36305821.
Dissecting TET2 Regulatory Networks in Blood Differentiation and Cancer. Lazarenkov A, Sardina JL$. Cancers (Basel). 2022 Feb 6;14(3):830. doi: 10.3390/cancers14030830. PMID: 35159097 Free PMC article.
Transcription Factors Drive Tet2-Mediated Enhancer Demethylation to Reprogram Cell Fate. Sardina JL*$, Collombet S, Tian TV, Gómez A, Di Stefano B, Berenguer C, Brumbaugh J, Stadhouders R, Segura-Morales C, Gut M, Gut IG, Heath S, Aranda S, Di Croce L, Hochedlinger K, Thieffry D, Graf T$. Cell Stem Cell. 2018 Nov 1;23(5):727-741.e9. doi: 10.1016/j.stem.2018.08.016. Epub 2018 Sep 13. PMID: 30220521.
Reprogramming human B cells into induced pluripotent stem cells and its enhancement by C/EBPα. Bueno C*, Sardina JL*, Di Stefano B, Romero-Moya D, Muñoz-López A, Ariza L, Chillón MC, Balanzategui A, Castaño J, Herreros A, Fraga MF, Fernández A, Granada I, Quintana-Bustamante O, Segovia JC, Nishimura K, Ohtaka M, Nakanishi M, Graf T, Menendez P$. Leukemia. 2016 Mar;30(3):674-82. doi: 10.1038/leu.2015.294. Epub 2015 Oct 26. PMID: 26500142.
C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells.
Di Stefano B, Sardina JL, van Oevelen C, Collombet S, Kallin EM, Vicent GP, Lu J, Thieffry D, Beato M, Graf T$. Nature. 2014 Feb 13;506(7487):235-9. doi: 10.1038/nature12885. Epub 2013 Dec 15. PMID: 24336202.