Inglés (Estados Unidos)

ibbtec@unican.es

Javier León Serrano (IP)

IBBTEC. Albert Einstein, 22; 39011 Santander
javier.leon@unican.es
942 201952
Transcriptional Control of Cancer and Cells and Stem Cells
Principal Investigator
Cancer
Department of Cell & Molecular Signalling

Prof Javier León was graduated in Biological Sciences and in Pharmacy, both in the Complutense University of Madrid (1978). He worked as resident in the University Hospital Marques de Valdecilla at Santander (1978-1980) to become Specialist in Microbiology. In 1983 he got his PhD in the University of Cantabria. After three years as postdoctoral researcher in New York University he returned to the University of Cantabria as Assistant Professor of Biochemistry and Molecular Biology (1987) and in 1994 he got the position of Full Professor. He has spent research stays for 2,5 years in the Fred Hutchinson Cancer Research Center, Seattle (1995, 2004) and Dana Farber Cancer Institute-Harvard Cancer Center, Boston (2004). Javier León has been the Chairman of the Department of Molecular Biology of the University of Cantabria, Director of the IBBTEC (2012-2016) and Vice-Chancellor of Research and Knowledge Transfer of the University of Cantabria (2016-2020).

Since 1989 has led a research group funded by 11 grants from the Spanish Ministry of Science, so far. He has also been PI of a Group of the Network of Cooperative Research in Cancer form the Spanish Heath Ministry (Instituto Carlos III). He has supervised 20 Ph Theses and has published 94 research papers in international indexed journals, being the first or corresponding author in 63% of them.His H-index is 33 (as Scopus) with more than 3360 citations (as Scopus).

In the last 10 years he has published 20 research papers, 80% of them published in journals of the first quartile of Impact Factor. The research topic of these papers has been a) the roles of the MYC oncogene in hematopoietic cell differentiation; b) cell cycle control and functional interaction of MYC with cell cycle inhibitor p27; c) translational research on the expression ad roles of MYC in chronic myeloid leukemia and lymphoma. Currently the group is working in a) the roles of MYC in Burkitt lymphoma and Epstein-Barr infection, and b) roles of MNT (transcription factor of the MYC network) in lymphoma and response to DNA damage.

Transcriptional Control in Cancer Cells and Stem Cells

Research lines

Roles of MYC network proteins MNT and MXD on cell proliferation
Functional interactions of MYC with cell cycle regulatory proteins
MYC target genes in leukemia/lymphoma
Function of the chromatin regulator CTCF in the hematopoietic differentiation
CTCF involvement in hematological malignancies, especially in lymphomas.
CTCF regulation of MYCand BCL6 oncogenes.

Funding

Oncoproteínas MYC Y CTCF en el control transcripcional de la diferenciación hematopoyética y en linfoma. SAF2014-53526R. CoIPs: Javier León y M. Dolores Delgado
Función de los reguladores transcripcionales CTCF y CTCF-L (BORIS) en la diferenciación hematopoyética normal y patológica. Instituto de Salud Carlos III. FIS11/00397
Terapia epigenética en linfomas de células B. Papel de los reguladores de cromatina de la familia CTCF. Entidad financiadora: Celgene S.L.U.

"Red Temática Investigación Cooperativa de Investigación en Cáncer" ISCIII-RETIC RD12/0036/0033. IP: Piero Crespo

"Functional interaction of MYC and CTCF in aggressive B-cell lymphoma and hematopoietic precursors" SAF2017-88026-R. CoIPs: M. Dolores Delgado y Javier León

ERK2 stimulates MYC transcription by anchoring CDK9 to the MYC promoter in a kinase activity-independent manner

Agudo-Ibáñez L, Morante M, García-Gutiérrez L, Quintanilla A, Rodríguez J, Muñoz A, León J, Crespo P.

Sci Signal. 2023 Jul 18;16(794):eadg4193.

JKST6, a novel multikinase modulator of the BCR-ABL1/STAT5 signaling pathway that potentiates direct BCR-ABL1 inhibition and overcomes imatinib resistance in chronic myelogenous leukemia

Aranda-Tavío H, Recio C, Martín-Acosta P, Guerra-Rodríguez M, Brito-Casillas Y, Blanco R, Junco V, León J, Montero JC, Gandullo-Sánchez L, McNaughton-Smith G, Zapata JM, Pandiella A, Amesty A, Estévez-Braun A, Fernández-Pérez L, Guerra B.

Biomed Pharmacother. 2021 Oct 19;144:112330.

The Multiple Faces of MNT and Its Role as a MYC Modulator.

Liaño-Pons J, Arsenian-Henriksson M, León J.

Cancers (Basel). 2021 Sep 18;13(18):4682.

A novel role of MNT as a negative regulator of REL and the NF-κB pathway

Liaño-Pons J, Lafita-Navarro MC, García-Gaipo L, Colomer C, Rodríguez J, von Kriegsheim A, Hurlin PJ, Ourique F, Delgado MD, Bigas A, Espinosa ML, León J.

Oncogenesis. 2021 Jan 8;10(1):5. doi: 10.1038/s41389-020-00298-4.

The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells

Lafita-Navarro MC, Liaño-Pons J, Quintanilla A, Varela I, Blanco R, Ourique F, Bretones G, Aresti J, Molina E, Carroll P, Hurlin P, Romero OA, Sanchez-Céspedes M, Eisenman RN, Delgado MD, León J.

J Biol Chem. 2020 Feb 14;295(7):2001-2017. doi: 10.1074/jbc.RA119.010389. Epub 2020 Jan 9.

Myc stimulates cell cycle progression through the activation of Cdk1 and phosphorylation of p27

García-Gutiérrez L, Bretones G, Molina E, Arechaga I, Symonds C, Acosta JC, Blanco R, Fernández A, Alonso L, Sicinski P, Barbacid M, Santamaría D, León J.

Sci Rep. 2019 Dec 10;9(1):18693. doi: 10.1038/s41598-019-54917-1.

Suppression of BCL6 function by HDAC inhibitor mediated acetylation and chromatin modification enhances BET inhibitor effects in B-cell lymphoma cells.

Cortiguera MG, García-Gaipo L, Wagner SD, León J, Batlle-López A, Delgado MD.

Sci Rep. 2019 Nov 11;9(1):16495. doi: 10.1038/s41598-019-52714-4.

MYC Oncogene Contributions to Release of Cell Cycle Brakes

García-Gutiérrez L, Delgado MD, León J.

GENES (Basel). 2019 Mar 22;10(3). pii: E244. doi: 10.3390/genes10030244.

CM363, a novel naphthoquinone derivative which acts as multikinase modulator and overcomes imatinib resistance in chronic myelogenous leukemia.

Guerra, B., Martín-Rodríguez, P., Díaz-Chico, J.C. McNaughton-Smith, G., Jiménez-Alonso, S., Hueso-Falcón, I., Montero, J., Blanco, R., León, J., Rodríguez, G., Estévez-Braun, A., Pandiella, A., Díaz-Chico, B.N. and Fernández-Pérez., L.*

Oncotarget. 8: 29679-29698 (2017) PMID:27557509.

MXD1 localizes in the nucleolus, binds UBF and impairs rRNA synthesis.

Lafita-Navarro, M.C., Blanco, R., Mata-Garrido, J., Liano-Pons, J., Tapia, O., García-Gutiérrez, L., García-Alegría, E., Berciano, M.T., Lafarga, M. and León, J.*

Oncotarget. 7:69536-69548 (2016) PMID: 27588501.

ODZ1 allows glioblastoma to sustain invasiveness through a Myc-dependent transcriptional upregulation of RhoA.

Talamillo, A. , Grande, L. , Ruiz-Ontañon, P. , Velasquez, C., Mollinedo, P., Torices, S., Sanchez-Gomez, P., Aznar, A., Esparis-Ogando, A., Lopez-Lopez, C. , Lafita, C., Berciano, M.T., Montero, J.A., Vazquez-Barquero, A. , Segura, V., Villagra, N.T., Pa

Oncogene. 36: 1733-1744 (2017). PMID: 27641332

ODZ1 allows glioblastoma to sustain invasiveness through a Myc-dependent transcriptional upregulation of RhoA.

Talamillo A, Grande L, Ruiz-Ontañon P, Velasquez C, Mollinedo P, Torices S, Sanchez-Gomez P, Aznar A, Esparis-Ogando A, Lopez-Lopez C, Lafita C, Berciano MT, Montero JA, Vazquez-Barquero A, Segura V, Villagra NT, Pandiella A, Lafarga M, Leon J, Martinez-

Oncogene. 2017 Mar 23;36(12):1733-1744. doi: 10.1038/onc.2016.341. Epub 2016 Sep 19.

NUMB inactivation confers resistance to imatinib in chronic myeloid leukemia cells.

Garcia-Alegría, E., Lafita-Navarro, M.C., Aguado, R., Garcia-Gutierrez, L., Sarnataro, K., Ruiz-Herguido, C., Martín, F., Bigas, A., Canelles, M., and León J.*

Cancer Lett 375:92-99 (2016). PMID: 26944313

CD3ε recruits Numb to promote TCR degradation.

Martin-Blanco, N., Jiménez-Teja, D., Bretones, G., Borroto, A., Caraballo, M., Screpanti, I., León, J., Alarcón, B., Canelles, M*

Int Immunol. 28:127-137 (2016). PMID: 26507128.

Myc and cell cycle control.

Bretones G, Delgado MD, León J.Biochim Biophys Acta. 2014 Apr 1. pii: S1874-9399(14)00073-X. doi: 10.1016/j.bbagrm.2014.03.013.

J.Biochim Biophys Acta. 2014Apr 1. pii: S1874-9399(14)00073-X. doi: 10.1016/j.bbagrm.2014.03.013.

MYC as therapeutical target in leukemia and lymphoma.

Cortiguera MG, Batlle-López A, Albajar M, Delgado MD, León J. Blood and Lymphatic Cancer: Targets and Therapy 2015:5 75–91.

[pubmed]

Sin3b interacts with myc and decreases myc levels.

Garcia-Sanz P, Quintanilla A, Lafita MC, Moreno-Bueno G, García-Gutierrez L, Tabor V, Varela I, Shiio Y, Larsson LG, Portillo F, Leon J. J Biol Chem. 2014 Aug 8;289(32):22221-36. doi: 10.1074/jbc.M113.538744.

[pubmed]

High p27 protein levels in chronic lymphocytic leukemia are associated to low Myc and Skp2 expression, confer resistance to apoptosis and antagonize Myc effects on cell cycle.

Caraballo JM, Acosta JC, Cortés MA, Albajar M, Gómez-Casares MT, Batlle-López A, Cuadrado MA, Onaindia A, Bretones G, Llorca J, Piris MA, Colomer D, León J.Oncotarget. 2014 Jul 15;5(13):4694-708.

[PubMed]

High p27 protein levels in chronic lymphocytic leukemia are associated to low Myc and Skp2 expression, confer resistance to apoptosis and antagonize Myc effects on cell cycle.

Caraballo JM, Acosta JC, Cortés MA, Albajar M, Gómez-Casares MT, Batlle-López A, Cuadrado MA, Onaindia A, Bretones G, Llorca J, Piris MA, Colomer D, León J. Oncotarget. 2014 Jul 15;5(13):4694-708.

[pubmed]

High p27 protein levels in chronic lymphocytic leukemia are associated to low Myc and Skp2 expression, confer resistance to apoptosis and antagonize Myc effects on cell cycle.

Caraballo, J.M., Acosta, J.C., Cortés, M.A:, Albajar, M., Gómez-Casares, M.T., Batlle-López, A., Cuadrado, M.A., Onaindia, A., Bretones, G., Llorca, J., Piris, M.A., Colomer, D., and León, J.*

Oncotarget 5:4694-4708 (2014). PMID: 25051361.

Sin3b interacts with Myc and decreases Myc levels

Garcia-Sanz P, Quintanilla A, Lafita MC, Moreno-Bueno G, Garcia-Gutierrez L, Tabor V, Varela I, Shiio Y, Larsson LG, Portillo F, Leon J.*

J Biol Chem. 289:22221-22236 (2014) PMID: 24951594.

MYC oncogene in myeloid neoplasias.

Delgado, M.D., Albajar, M., Gomez-Casares, M.T., Batlle, A., and León, J. Clin Trans Oncol, 15: 87-94 (2013) .PMID: 22911553.

[pubmed]

MYC accelerates p21(CIP) -induced megakaryocytic differentiation involving early mitosis arrest in leukemia cells.

Muñoz-Alonso MJ, Ceballos L, Bretones G, Frade P, León J, Gandarillas A. J Cell Physiol. 227: 2069–2078 (2012).

[pubmed]

MYC antagonizes the differentiation induced by imatinib in chronic myeloid leukemia cells through down-regulation of p27KIP1 .

Gómez-Casares, M.T. García-Alegria, E., López-Jorge, C.E., Ferrándiz, N., Blanco, R., Alvarez, S., Vaqué, J.P., , Bretones, G., Caraballo, J.M., Sanchez-Bailón, P., Delgado, M.D., Martin-Perez, J., Cigudosa, J.C., and León, J. Oncogene 32:2239- 2246 (2012

[pubmed]

MYC in chronic myeloid leukemia: induction of aberrant DNA synthesis and association with poor response to imatinib.

Albajar, M., Gómez-Casares, M.T., Llorca, J., Mauleon, J., Vaqué, J.P., Acosta, J.C., Bermúdez, A., Donato, N., Delgado, M.D. and León, J. Mol Cancer Res 9: 564-576 (2011).

[pubmed]

Skp2 oncogene is a direct Myc target gene and Myc downregulates p27kip1 through Skp2 in human leukemia cells.

Bretones, G., Acosta J.C:, Caraballo, J., Ferrandiz, N., Gómez-Casares, M.T., Albajar, M., Blanco, R., Ruiz, P., Hung, W-C., Albero, M.P., Perez-Roger, I. and León J. J Biol Chem. 286: 9815-25 (2011).

[pubmed]

Myc roles in hematopoiesis and leukemia.

Delgado, M.D and León, J. Genes &Cancer (2010) 1: 605–616. Review

[pubmed]

p21Cip1 confers resistance to imatinib in human chronic myeloid leukemia cells.

Ferrandiz, N, Caraballo, J. M., Albajar, M, Gomez-Casares, M.T., López-Jorge, C.E., Blanco, R., Delgado, M.D. and Leon, J. Cancer Lett 292: 133-139 (2010).

[pubmed]

Mª Dolores Delgado Villar (IP)

Lorena García Gaipo

Lucía García Gutiérrez

Vanessa Junco Ruisánchez

IBBTEC

Instituto de Biomedicina y Biotecnología de Cantabria.
PCTCAN - Cl. Albert Einstein, 22
39011 Santander

Javier León Serrano (IP)

​Transcriptional Control in Cancer Cells and Stem Cells

Research lines

Funding

ERK2 stimulates MYC transcription by anchoring CDK9 to the MYC promoter in a kinase activity-independent manner

JKST6, a novel multikinase modulator of the BCR-ABL1/STAT5 signaling pathway that potentiates direct BCR-ABL1 inhibition and overcomes imatinib resistance in chronic myelogenous leukemia

The Multiple Faces of MNT and Its Role as a MYC Modulator.

A novel role of MNT as a negative regulator of REL and the NF-κB pathway

The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells

Myc stimulates cell cycle progression through the activation of Cdk1 and phosphorylation of p27

Suppression of BCL6 function by HDAC inhibitor mediated acetylation and chromatin modification enhances BET inhibitor effects in B-cell lymphoma cells.

MYC Oncogene Contributions to Release of Cell Cycle Brakes

CM363, a novel naphthoquinone derivative which acts as multikinase modulator and overcomes imatinib resistance in chronic myelogenous leukemia.

MXD1 localizes in the nucleolus, binds UBF and impairs rRNA synthesis.

ODZ1 allows glioblastoma to sustain invasiveness through a Myc-dependent transcriptional upregulation of RhoA.

ODZ1 allows glioblastoma to sustain invasiveness through a Myc-dependent transcriptional upregulation of RhoA.

NUMB inactivation confers resistance to imatinib in chronic myeloid leukemia cells.

CD3ε recruits Numb to promote TCR degradation.

Myc and cell cycle control.

MYC as therapeutical target in leukemia and lymphoma.

Sin3b interacts with myc and decreases myc levels.

High p27 protein levels in chronic lymphocytic leukemia are associated to low Myc and Skp2 expression, confer resistance to apoptosis and antagonize Myc effects on cell cycle.

High p27 protein levels in chronic lymphocytic leukemia are associated to low Myc and Skp2 expression, confer resistance to apoptosis and antagonize Myc effects on cell cycle.

High p27 protein levels in chronic lymphocytic leukemia are associated to low Myc and Skp2 expression, confer resistance to apoptosis and antagonize Myc effects on cell cycle.

Sin3b interacts with Myc and decreases Myc levels

MYC oncogene in myeloid neoplasias.

MYC accelerates p21(CIP) -induced megakaryocytic differentiation involving early mitosis arrest in leukemia cells.

MYC antagonizes the differentiation induced by imatinib in chronic myeloid leukemia cells through down-regulation of p27KIP1 .

MYC in chronic myeloid leukemia: induction of aberrant DNA synthesis and association with poor response to imatinib.

Skp2 oncogene is a direct Myc target gene and Myc downregulates p27kip1 through Skp2 in human leukemia cells.

Myc roles in hematopoiesis and leukemia.

p21Cip1 confers resistance to imatinib in human chronic myeloid leukemia cells.

Mª Dolores Delgado Villar (IP)

Lorena García Gaipo

Lucía García Gutiérrez

Vanessa Junco Ruisánchez

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Transcriptional Control in Cancer Cells and Stem Cells