Meritxell Alberich Jorda
Meritxell Alberich Jorda, Ph.D.
Meritxell Alberich Jorda, Ph.D.
Address:  Institute of Molecular Genetics of the ASCR, v. v. i.
Vídeňská 1083
142 20 Prague 4, Czech Republic
 
Phone:+420 241 062 589
Fax:+420 244 472 282
E-mail:alberich@img.cas.cz

Biography

Born:  July 9, 1975
Barcelona, Spain
Education: 1999-2003, PhD in Medicine (ErasmusMC, Rotterdam Medical University, The Netherlands)
1994-1999, Biology degree (Universitat de Barcelona, Facultat de Biologia, Barcelona, Spain)
.................

Research experience

2015-presentGroup leader, Department of Hemato-oncology, Institute of Molecular Genetics, Prague, Czech Republic
2012-2014Principal Investigator, Department of Molecular Immunology, Institute of Molecular Genetics, Prague, Czech Republic
2013-presentAffiliation to the 2nd faculty of Medicine, Charles University, Department of Pediatric Hematology and Oncology, Prague, Czech Republic
2005-2012Postdoctoral Fellow, Harvard Medical School – Harvard Stem Cell Institute and BIDMC Department of Hematology/Oncology, Boston, USA

International fellowships

2005-2007European Hematology Association Research Fellowship (Harvard University, Boston, USA)
1998-1999 Erasmus Exchange Program Fellowship (Leiden University, The Netherlands)
1997Summer Erasmus Program Cell Cycle and Development Fellowship (Banyuls sur Mer, France)

Awards and Honors

2016-present Member of the Fellowship and Grant committee at the European Hematology Association
2006-present Abstract reviewer for the European Hematology Association
2010Oral presentation at the “EHA Presidential Session”: presentation of the best 6 abstracts (out of approx. 2100) at the 15th European Hematology Association congress
2007-2008Member of the 12th and 13th European Hematology Association scientific committee
2006Member of the 11th European Hematology Association scientific and educational committee

Selected Publications

  • Hartmann JU, Bräuer-Hartmann D, Kardosova M, Wurm AA, Wilke F, Schödel C, Gerloff D, Katzerke C, Krakowsky R, Namasu CY, Bill M, Schwind S, Müller-Tidow C, Niederwieser D, Alberich-Jorda M, Behre G: MicroRNA-143 targets ERK5 in granulopoiesis and predicts outcome of patients with acute myeloid leukemia. (Cell Death Dis 2018 Jul 26;9(8): 814.)
  • Kardosova M, Zjablovskaja P, Danek P, Angelisova P, Lobo de Figueiredo-Pontes L, Welner RS, Brdicka T, Lee S, Tenen DG, Alberich-Jorda M: C/EBPγ is dispensable for steady-state and emergency granulopoiesis. (Haematologica 2018 Aug;103(8):e331-e335.)
  • Rejlová K, Musilová A, Škvárová Kramarzová K, Žaliová M, Fišer K, Alberich-Jorda M, Trka J, Starková J: LOW HOX gene expression in PML-RARα-POSITIVE leukemia results from suppressed histone demethylation. (Epigenetics 2018;13(1):73-84.)
  • Zjablovskaja P, Danek P, Kardosova M, Alberich-Jorda M: Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells. (J Vis Exp 2018 Feb 21;(132).)
  • Gonzalez D, Luyten A, Bartholdy B, Zhou Q, Kardosova M, Ebralidze A, Swanson KD, Radomska H, Zhang P, Kobayashi SS, Welner RS, Levantini E, Steidl U, Chong G, Collombet S, Choi MH, Friedman AD, Scott LM, Alberich-Jorda M, Tenen DG: ZNF143 is an important regulator of the myeloid transcription factor C/EBPα. (J Biol Chem. 2017 Nov 17;292(46):18924-18936.)
  • Rychtarcikova Z, Lettlova S, Tomkova V, Korenkova V, Langerova L, Simonova E, Zjablovskaja P, Alberich-Jorda M, Neuzil J, Truksa J: Tumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism. (Oncotarget 2017 8(4): 6376–6398.)
  • Wurm AA, Zjablovskaja P, Kardosova M, Gerloff D, Bräuer-Hartmann D, Katzerke C, Hartmann JU, Benoukraf T, Fricke S, Hilger N, Müller AM, Bill M, Schwind S, Tenen DG, Niederwieser D, Alberich-Jorda M, Behre G: Disruption of the C/EBPα-miR-182 balance impairs granulocytic differentiation. (Nat Commun 2017 8(1): 46.)
  • Zimmermannova O, Doktorova E, Stuchly J, Kanderova V, Kuzilkova D, Strnad H, Starkova J, Alberich-Jorda M, Falkenburg JHF, Trka J, Petrak J, Zuna J, Zaliova M: An activating mutation of GNB1 is associated with resistance to tyrosine kinase inhibitors in ETV6-ABL1-positive leukemia. (Oncogene 2017.)
  • Zjablovskaja P, Kardosova M, Danek P, Angelisova P, Benoukraf T, Wurm AA, Kalina T, Sian S, Balastik M, Delwel R, Brdicka T, Tenen DG, Behre G, Fiore F, Malissen B, Horejsi V, Alberich-Jorda M: EVI2B is a C/EBPα target gene required for granulocytic differentiation and functionality of hematopoietic progenitors. (Cell Death Differ 2017.)
  • Yong KJ, Basseres DS, Welner RS, Zhang WC, Yang H, Yan B, Alberich-Jorda M, Zhang J, de Figueiredo-Pontes LL, Battelli C, Hetherington CJ, Ye M, Zhang H, Maroni G, O'Brien K, Magli MC, Borczuk AC, Varticovski L, Kocher O, Zhang P, Moon YC, Sydorenko N, Cao L, Davis TW, Thakkar BM, Soo RA, Iwama A, Lim B, Halmos B, Neuberg D, Tenen DG, Levantini E: Targeted BMI1 inhibition impairs tumor growth in lung adenocarcinomas with low CEBPα expression. (Science Translational Medicine, 2016 Aug 3;8(350):350ra104.)
  • Hermanova I, Arruabarrena-Aristorena A, Valis K, Nuskova H, Alberich-Jorda M, Fiser K, Fernandez-Ruiz S, Kavan D, Pecinova A, Niso-Santano M, Zaliova M, Novak P, Houstek J, Mracek T, Kroemer G, Carracedo A, Trka J, Starkova J: Pharmacological inhibition of fatty-acid oxidation synergistically enhances the effect of l-asparaginase in childhood ALL cells. (Leukemia 2016 30(1): 209-18.)
  • Kazerounian S, Ciarlini PD, Yuan D, Ghazvinian R, Alberich-Jorda M, Joshi M, Zhang H, Beggs AH, Gazda HT: Development of Soft Tissue Sarcomas in Ribosomal Proteins L5 and S24 Heterozygous Mice. (J Cancer 2016 7(1): 32-6.)
  • Janeckova L, Fafilek B, Krausova M, Horazna M, Vojtechova M, Meritxell Alberich-Jorda, Sloncova E, Galuskova K, Sedlacek R, Anderova M, Korinek V. Wnt signaling inhibition deprives small intestinal stem cells of clonogenic capacity. (Genesis, 2016 Feb 11.)
  • Balastik M, Zhou XZ, Alberich-Jorda M, Weissova R, Žiak J, Pazyra-Murphy MF, Cosker KE, Machonova O, Kozmikova I, Chen CH, Pastorino L, Asara JM, Cole A, Sutherland C, Segal RA, Lu KP: Prolyl Isomerase Pin1 Regulates Axon Guidance by Stabilizing CRMP2A Selectively in Distal Axons. (Cell Rep 2015 13(4): 812-28.)
  • Drobek A, Kralova J, Skopcova T, Kucova M, Novák P, Angelisová P, Otahal P, Alberich-Jorda M, Brdicka T: PSTPIP2, a Protein Associated with Autoinflammatory Disease, Interacts with Inhibitory Enzymes SHIP1 and Csk. (J Immunol 2015 195(7): 3416-26.)
  • Adam Liss, Chia-Huey Ooi, Polina Zjablovskaja, Touati Benoukraf, Hanna S. Radomska, Chen Ju, Mengchu Wu, Martin Balastik, Ruud Delwel, Tomas Brdicka, Patrick Tan, Daniel G. Tenen*, and Meritxell Alberich-Jorda*. The gene signature in CCAAT-enhancer-binding protein α dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors. (Haematologica, 2014 Apr;99(4):697-705.)
  • Hong Zhang, Meritxell Alberich-Jorda, Giovanni Amabile, Henry Yang, Philipp B. Staber, Annalisa DiRuscio, Rob Welner, Alex Ebralidze, Junyan Zhang, Elena Levantini, Veronique Lefebvre, Peter JM Valk, Ruud Delwel, Maarten Hoogenkamp, Clauss Nerlov, Jorg Cammenga, Borja Saez, David T. Scadden, Constanze Bonifer, Min Ye, and Daniel G. Tenen. Sox4 is a key oncogenic target in C/EBPa mutant acute myeloid leukemia. (Cancer Cell, 2013 Nov 11;24(5):575-88.)
  • Annalisa DiRuscio, Alex Ebralidze, Touati Benoukraf, Giovanni Amabile, Loyal Goff, Pu Zhang, Meritxell Alberich-Jorda, Sriharsa Pradhan, Maria Figueroa, Francesco D'Alo, Mengchu Wu, Giuseppe Leone, John Rinn, Daniel G. Tenen. DNMT1-interacting RNAs block gene specific DNA methylation. (Nature, 2013 Nov 21;503(7476):371-6)
  • Min Ye , Hong Zhang , Giovanni Amabile , Henry Yang , Philipp Staber , Pu Zhang , Elena Levantini, Meritxell Alberich-Jorda , Junyan Zhang , Akira Kawasaki, and Daniel G. Tenen. C/EBPα controls acquisition and maintenance of adult hematopoietic stem cell quiescence (Nature Cell Biology, 2013 Apr;15(4):385-94.)
  • Philipp B Staber, Pu Zhang, Min Ye, Robert Welner, César Nombela-Arrieta, Christian Bach, Marc Kerenyi, Boris A Bartholdy, Hong Zhang, Meritxell Alberich-Jorda, Sanghoon Lee, Henry Yang, Felicia Ng, Junyan Zhang, Mathias Leddin, Leslie E Silberstein, Gerald Hoefler, Stuart H Orkin, Berthold Gottgens, Frank Rosenbauer, Gang Huang, and Daniel G. Tenen. Sustained PU.1 Levels Balance Cell Cycle Regulators to Prevent Exhaustion of Adult Hematopoietic Stem Cells. (Molecular Cell, 2013 Mar 7;49(5):934-46.)
  • Meritxell Alberich-Jorda, Bas Wouters, Martin Balastik, Clara Shapiro-Koss, Hong Zhang, Annalisa DiRuscio, Hanna S. Radomska, Alex K. Ebralidze, Giovanni Amabile, Min Ye, Junyan Zhang, Irene Lowers, Roberto Avellino, Ari Melnick, Maria E. Figueroa, Peter J.M. Valk, Ruud Delwel, Daniel G. Tenen. C/EBP deregulation results in differentiation arrest in acute myeloid leukemia. (Journal of Clinical Investigation, 2013 January 2; 123(1): 526.)
  • Hanna S. Radomska*, Meritxell Alberich-Jorda*, Britta Will, David Gonzalez, Ruud Delwel and Daniel G. Tenen. Targeting the cdc2-C/EBPγ pathway induces differentiation of acute myeloid leukemias with FLT3-ITD activating mutations. (Journal of Clinical Investigation, 2012 Aug 1; 122(8):2955-66, * Equal contribution)
  • Elena Levantini, Sanghoon Lee, Hanna S. Radomska, Christopher J. Hetherington, Meritxell Alberich-Jorda, Giovanni Amabile et al. RUNX1 regulates human CD34 gene expression in long-term hematopoietic stem cells by mediating interaction with a distal regulatory element. (EMBO J, 2011 Aug 26; 30(19):4059-70)
  • Britta Will, Tanya Siddiqi, Meritxell Alberich-Jorda, Takeshi Shimamura, Katarina Luptakova, Philipp B. Staber, Daniel B. Costa, Ulrich Steidl, Daniel G. Tenen and Susumu S. Kobayashi. Apoptosis induced by JAK2 inhibition is mediated by Bim and enhanced by the BH3 mimetic ABT-737 in JAK2 mutant human erythroid cells. (Blood, 2010 Apr 8;115(14):2901-9)
  • Karen B. O’Brien, Meritxell Alberich-Jorda, Neelu Yadav, Olivier Kocher, Annalisa DiRuscio, Alexander Ebralidze, Elena Levantini, Natasha J. L. Sng, Manoj Bhasin, Tyler Caron, Daehoon Kim, Ulrich Steidl, Gang Huang, Balázs Halmos, Scott J. Rodig, Mark T. Bedford, Daniel G. Tenen and Susumu Kobayashi. CARM1 is required for proper control of proliferation and differentiation of pulmonary epithelial cells. (Development, 2010 Jul;137(13):2147-56)
  • Florence C. Guibal*, Meritxell Alberich-Jorda*, Hideyo Hirai, Alexander Ebralidze, Elena Levantini, Annalisa DiRuscio, Pu Zhang, Barbara A.Santana-Lemos, Donna Neuberg, Amy J. Wagers, Eduardo M. Rego, Daniel G. Tenen. Identification of a myeloid committed progenitor as the cancer-initiating cell in acute promyelocytic leukemia. (Blood, 2009 Dec 24, *Equal contribution)
  • Alexander Ebralidze, Florence Guibal, Ulrich Steidl, Pu Zhang, Sanghoon Lee, Boris Bartholdy, Meritxell Alberich-Jorda, Victoria Petkova, et al. PU.1 expression is modulated by the balance of functional sense and antisense RNAs regulated by a shared cis-regulatory element (Genes and Development, 2008 Aug 1;22(15):2085-92)
  • Bas J. Wouters, Meritxell Alberich-Jorda, Claudia A.J. Erpelinck-Verschueren, Dennis Tielemans, Anton W. Langerak, Peter J.M. Valk, Bob Löwenberg, Daniel G. Tenen, Ruud Delwel. Distinct gene expression profiles of acute myeloid/T-lymphoid leukemia with silenced CEBPA and mutations in NOTCH1. (Blood, 2007 Nov 15;110(10):3706-14)
  • Meritxell Alberich-Jorda, Nazik Rayman, Marjolein Tas, Sandra E. Verbakel, Natalia Battista, Kirsten van Lom, Bob Löwenberg, Mauro Maccarrone, and Ruud Delwel. The peripheral cannabinoid receptor Cb2, frequently expressed on AML blasts, either induces a neutrophilic differentiation block or confers abnormal migration properties in a ligand-dependent manner. (Blood, 2004. 104(2):526-34)
  • Meritxell Alberich-Jorda, Bob Löwenberg, and Ruud Delwel. The peripheral cannabinoid receptor Cb2, a novel oncoprotein, induces a reversible block in neutrophilic differentiation. (Blood, 2003. 15;101(4):1336-1343)
  • Meritxell Alberich-Jorda, Sandra E. Verbakel, Peter J. Valk, Yolanda Vankan-Berkhoudt, Mauro Maccarrone, Allessandro Finazzi-Agro, Bob Lowenberg, and Ruud Delwel. Hematopoietic cells expressing the peripheral cannabinoid receptor migrate in response to the endocannabinoid 2-arachidonoylglycerol. (Blood, 2002. 15;99(8):2786-93)
  • Marieke Joosten, Peter J Valk, Meritxell Alberich-Jorda, Yolanda Vankan-Berkhoudt, Sandra E Verbakel, Marion van den Broek, Antoinette Beijen, Bob Lowenberg, and Ruud Delwel. Leukemic predisposition of pSca-1/Cb2 transgenic mice. (Experimental Hematology, 2002. 30:142-149)

Research Interest

Acute myeloid leukemia (AML) is a malignant hematopoietic disease that represents over 90% of acute leukemias in adults, and is characterized by an accumulation of immature and non-functional blood cells in the bone marrow and blood. All blood cells are derived from a small population of cells called hematopoietic stem cells (HSC), which are pluripotent and can differentiate into all hematopoietic lineages. Transcription factors function as key regulators of hematopoiesis by regulating the processes of self-renewal, proliferation and differentiation of HSC. Minute changes in expression of transcription factors have been shown to deregulate hematopoiesis and aberrations in myeloid transcription factors have been observed in AML patients.

Our research team is particularly interested in the CCAAT/enhancer binding protein (C/EBP) transcription factor family, which regulates the commitment of HSC towards the myeloid lineage. C/EBPs are DNA-binding proteins in which six core members have been identified: C/EBPα, C/EBPβ C/EBPδ, C/EBPε, C/EBPγ and C/EBPζ. We investigate how C/EBPs regulate granulocytic production, whether they are mutated or deregulated during leukemogenesis, and how these alterations participate in the development of human acute myeloid leukemia (AML). Using in vitro and in vivo models, in combination with genome-wide screenings, we are currently pursuing the following projects:

  1. Function of C/EBPγ in normal and malignant hematopoiesis: Recently, we observed that CEBPG is highly upregulated in AML samples characterized by CEBPA hypermethylation/silencing, and demonstrated that these elevated C/EBPγ levels contribute to the development of AML. Our data points to C/EBPγ playing an essential role in granulocytic development, but the mechanisms underlying C/EBPγ induced transformation remain poorly understood. In this project, we aim to identify C/EBPγ target genes and understand the mechanisms involved in C/EBPγ induced transformation.
  2. Modulation of C/EBPα target genes to restore granulocytic differentiation in human AML: C/EBPα plays a crucial role in the commitment of multipotent progenitor cells into the myeloid lineage, and mice deficient in C/EBPα are characterized by a specific block in the transition from CMP (common myeloid progenitors) to GMP (granulocyte-macrophage progenitors), resulting in the lack of mature and functional granulocytes. Defects in CEBPA, such as differentiation-deficient mutations, post-transcriptional modifications, post-translational inhibition and epigenetic regulation, have been shown to inhibit C/EBPα function in AML. In this project, we aim to define C/EBPα target genes and identify small-molecules able to reactivate these targets, ultimately resulting in restoration of granulocytic differentiation in AML.

Current Ph.D. students

foto - Grušanović Srdjan, M.Sc.
S. Grušanović
foto - Miroslava Adamcová , Ph.D.
M. Adamcová
foto - Petr Daněk, M. Sc.
Petr Daněk

 

Other Lab Members

foto - Monika Burócziová
Monika Burócziová
(postdoc)
foto - Marek Jedlička
Marek Jedlička
(master student)

 

Past students

C. Lozano Asencio, Ph.D. student
Berta Díez, Undergraduate student
Clara Shapiro-Koss, Medical student
P. Zjablovskaja, Ph.D. student

Funding

Current funding

2018-2022    AZV, NV18-07-00129 (Co-PI) - Role of leukemia cell metabolism in disease manifestation, progression and therapy response
2018-2020    GACR, 18-08577S - The transcription factor C/EBPg as a novel regulator in mast cell development and function
2017-2019    GACR, 17-02117S - Mechanisms regulating normal and leukemic hematopoietic stem cells: role of the b-catenin/Tcf signaling pathway
2017-2019    GAUK, 1278217 - Expansion of Hematopoietic Progenitors for Stem Cell Transplantation

Previous funding

2015-2018    AZV, 15-28848A - Increased sensitivity of leukemic patients to treatment with L-asparaginase by metabolic modulation
2015-2017    GAUK, 341-015 - Role of the transcription factor CEBPγ in emergency granulopoiesis
2015-2017    GACR, GA15-03796S - Function of the transmembrane protein Evi2b in hematopoiesis
2013-2015    Reintegration grant of the Ministry of Education, Youth and Sports, Czech Republic

 

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