PROJECT
SUPERVISORS
Project Supervisor
Marcus Buschbeck
Background
I started my scientific career by studying biochemistry at the University of Frankfurt in Germany and also studied two years of chemistry. I gained my first research experience during a number of internships including a longer one at the University of Oxford. Back then I became excited about how cells receive, process and transmit signals and decided to join the team of Axel Ullrich at the Max-Planck-Institute of Biochemistry in Munich for my PhD thesis. While I always knew that I would like to stay in science, it took me most of my last year as a PhD student to decide what topic I would like to approach next as a postdoc.
TThe early 2000 years were the time when we started to realize that chromatin modifications provide the molecular basis for epigenetic regulation. I found this fascinating and decided to join the junior group of Luciano Di Croce at the then newly founded Centre for Genomic Regulation in Barcelona. I have been working on the topic since. In 2009 I started to do so as a group leader and in 2015 I joined the Josep Carreras Leukaemia Research Institute where I still am today. I believe that basic and applied research can learn a lot from each other.
Research
As group we are fascinated about how a single genome can give rise to hundreds of cell types. We want to know how the regulation of chromatin including its packaging into the three-dimensional space of the nucleus determines how the genetic information is used and interpreted. In other words, we want to understand how epigenetics works. We focus much of our work on blood cancers such as acute myeloid leukemia and myelodysplastic syndromes. In addition to our fundamental research, we explore if chromatin regulation could be exploited as a point for therapeutic intervention.
An exciting and poorly understood aspect is how nuclear metabolism impacts on chromatin function. In particular, we are interested how metabolic changes occurring in leukemia alter chromatin function and gene expression. This includes aberrant levels of metabolites, altered fluxes of metabolic pathways and the enrichment of metabolic enzymes on chromatin. In the past years, we have focused much of our fundamental work on deciphering the function of histone variants with macrodomains. Since macrodomains are potential metabolite-binding modules, we hypothesize that they could provide a potential sensory function for metabolic states. We believe that a better understanding of what happens in leukemia will allow us to find interventions and improve current therapies
Publications
Evolution of a histone variant involved in compartmental regulation of NAD metabolism.
Guberovic I, Hurtado-Bagès S, Rivera-Casas C, Knobloch G, Malinverni R, Valero V, Leger MM, García J, Basquin J, Gómez de Cedrón M, Frigolé-Vivas M, Cheema MS, Pérez A, Ausió J, Ramírez de Molina A, Salvatella X, Ruiz-Trillo I, Eirin-Lopez JM, Ladurner AG, Buschbeck M.Nat Struct Mol Biol. 2021 Dec;28(12):1009-1019. doi: 10.1038/s41594-021-00692-5.
MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+consumption.
Posavec Marjanović M, Hurtado-Bagès S, Lassi M, Valero V, Malinverni R, Delage H, Navarro M, Corujo D, Guberovic I, Douet J, Gama-Perez P, Garcia-Roves PM, Ahel I, Ladurner AG, Yanes O, Bouvet P, Suelves M, Teperino R, Pospisilik JA, Buschbeck M.Nat Struct Mol Biol. 2017 Nov;24(11):902-910. doi: 10.1038/nsmb.3481. Epub 2017 Oct 9.PMID: 28991266
Inhibition of CBP synergizes with the RNA-dependent mechanisms of Azacitidine by limiting protein synthesis.
Diesch J, Le Pannérer MM, Winkler R, Casquero R, Muhar M, van der Garde M, Maher M, Herráez CM, Bech-Serra JJ, Fellner M, Rathert P, Brooks N, Zamora L, Gentilella A, de la Torre C, Zuber J, Götze KS, Buschbeck M.Nat Commun. 2021 Oct 18;12(1):6060. doi: 10.1038/s41467-021-26258-z.PMID: 34663789
Different Gene Sets Are Associated With Azacitidine Response In Vitro Versus in Myelodysplastic Syndrome Patients.
Le Pannérer MM, Diesch J, Casquero R, Maher M, Garcia O, Haferlach T, Zuber J, Kündgen A, Götze KS, Buschbeck M.Hemasphere. 2022 Oct 25;6(11):e792. doi: 10.1097/HS9.0000000000000792. eCollection 2022 Nov.PMID: 36310757