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Cellular Differentiation

imatge Central Grup Recerca

Scientific Team

Researchers
Maribel Parra
Postdoctoral researchers
Bruna Barneda
Predoctoral researchers
Lidia Roman
Technicians
Olga Maria Collazo

Research lines

Adult hematopoiesis is characterized by the generation of all blood cell types. To achieve this, hematopoietic stem cells (HSCs) differentiate into common myeloid progenitors (CMPs) and lymphoid-primed multipotent progenitors (LMPPs). CMPs give rise to megakaryocyte/erythrocyte progenitors (MEPs) and granulocyte/macrophage progenitors (GMPs), whereas LMPPs still have the capacity to choose between the myelomonocytic and lymphoid lineages. Common lymphoid progenitors (CLPs) have the potential to differentiate into B and T lymphocytes, as well as natural killer (NK) cells. Since the stability of every differentiation step is critical, each transition is tightly regulated at the transcriptional level through the action of lineage-restricted transcription factors that induce genes characteristic of particular cellular states. Importantly, deregulation of particular transcriptional programs leads to the development of hematological malignancies such as leukemias and lymphomas. Surprisingly, very little is known on the role of gene transcriptional repressors, such as histone deacetylases (HDACs), in the lineage specification and differentiation of hematopoietic cells. Once a progenitor has chosen to become a particular cell type, it will both up-regulate lineage specific genes, and repress inappropriate genes characteristic of other cellular lineages.

The main goals of our laboratory are:

1.      To investigate the role of class IIa HDACs in the lineage commitment and differentiation of B lymphocytes.

2.       To investigate the potential role of class IIa HDACs in the development of hematological malignancies.


1. Rodríguez-Ubreva J, Ciudad L, Gómez-Cabrero D, Parra M, Bussmann LH, di Tullio A, Kallin EM, Tegnér J, Graf T, Ballestar E. Pre-B cell to macrophage transdifferentiation without significant promoter DNA methylation changes. Nucleic Acids Res. 2012. 40(5):1954-1968.

 

2. Rafati H*, Parra M*, Hakre S, Moshkin Y, Verdin E, Mahmoudi T. Repressive LTR nucleosome positioning by the BAF complex is required for HIV latency. PLoS Biol. 2011. 9(11):e1001206. (*First co-authors)

 

3. Parra M* and Verdin E*. Regulatory signal transduction pathways for class IIa histone deacetylases. Current Opinion in Pharmacology. 2010. 10(4): 450-60 (*corresponding authors) (invited review)

 

4. Bussmann L*, Schubert A*, Vu Manh T*, De Andres L, Desbordes SC, Parra M, Zimmermann T, Rapino F, Rodriguez-Ubreva J, Ballestar E and Graf T. A robust and highly efficient immune cell reprogramming system. Cell Stem Cell. 2009. 5:554-66 (*First co-authors) (selected for the journal cover)

 

5.  Parra M. Epigenetic events during B lymphocyte development. Epigenetics. 2009. 4(7): 462-68 (invited review) 

 

6. Wang S, Li X, Parra M, Verdin E, Bassel-Duby R, Olson EN. Control of endothelial cell proliferation and migration by VEGF signaling to histone deacetylase 7. Proc Natl Acad Sci U S A. 2008. 105(22):7738-43 

 

7. Parra M, Mahmoudi T and Verdin E. Myosin phosphatase dephosphorylapes HDAC7, controls its nucleo-cytoplasmic shuttling and inhibits apoptosis in thymocytes. Genes and Development. 2007. 21(6):638-43 

 

8. Mahmoudi T, Parra M, Vries R, Kauder S, Verrijzer P, Ott M and Verdin E. The SWI/SNF Chromatin-Remodeling Complex is a Cofactor for Tat Transactivation of the HIV Promoter. Journal of Biological Chemistry. 2006. 281(29): 19960-8 

 

9. Parra M,Kasler H, McKinsey TA, Olson EN and Verdin E. Protein kinase D1 phosphorylates HDAC7 and induces its nuclear export after T-cell receptor activation. Journal of Biological Chemistry. 2005. 280(14): 13762-70

imatge personal
 

Group leader

Maribel Parra
Telephone  
+34 932607133
E-mail  
mparra@idibell.cat
 
© 2013 Institut d'Investigació Biomèdica de Bellvitge



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