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  • Laboratorio 5 - Sandra

Dra. Sandra Blanco Benavente


Biografía

Research during my PhD and post-doctorate period

During my PhD and my post-doctorate, I have been engaged in finding the molecular mechanisms that lead to cancer. Initially during my PhD, at the Institute of Molecular and Cellular Biology of Cancer (Salamanca, Spain), I studied post-translation modifications (phosphorylation), and particularly dysfunctional kinases as possible targets for cancer therapy under the supervision of Prof. Pedro A. Lazo. During my post-doctorate, in the group of Dr. Michaela Frye at the Wellcome Trust – MRC Cambridge Stem Cell Institute – University of Cambridge, I studied the functional role of post-transcriptional RNA modifications in tissue homeostasis and the impact of their dysregulation in diseases such as cancer. My work largely contributed to the knowledge we have gained to date on the functional role of post-transcriptional modifications and pathological outcomes of their dysregulation, in particular 5-methylcytosine deposition in RNA. There are around 100 known covalent RNA modifications, yet our knowledge about their occurrence and physiological function in mammals is still very limited. My studies have demonstrated that cytosine-5 RNA methylation has an essential role in cellular processes including self-renewal and stress responses in tissue and cancer stem cells.

By combining stem cell biology and mouse genetics, I found that cytosine-5 RNA methylation (m5C) is a novel mechanism by which stem and progenitor cells (both in tissue and in cancer) balance self-renewal and differentiation/proliferation properties 1-5. By using novel transcriptome‐wide sequencing approaches together with mouse genetics, I determined that cytosine-5 RNA methylation is a widespread modification in coding, non-coding RNAs and mainly transfer RNAs (tRNAs) 1,6-10 which regulated self-renewal in tissue stem cells but also sensitivity to stress in tumour initiating cells 4,5,9. Thus, my work in the laboratory of M. Frye was innovative and shed light on novel dysfunctional and targetable molecular pathways in cancer. Our findings were pioneers in exploring yet unknown mechanisms in stem cell and cancer biology and established the emergence of a novel research field coined as the Epitranscriptome. Moreover, our studies were the first to mechanistically link altered RNA methylation and cancer, and set novel road maps to chart the discovery of novel therapeutic strategies to treat cancer 5,11,12.

After my postdoctoral position, I was awarded a Ramón y Cajal fellowship (Sept’2016) that enabled my establishment as a Junior PI at CIC bioGUNE (Spain). Since then my research has focused on epitranscriptomics in cancer, in particular defining the molecular traits that the fluctuating epitranscriptome may confer to cancer cells and cancer initiating cells.

References

1   Blanco, S, Kurowski, A, Nichols, J, Watt, FM, Benitah, SA & Frye, M. The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate. PLoS genetics 7, e1002403, doi:10.1371/journal.pgen.1002403 (2011).

2   Hussain, S, Tuorto, F, Menon, S, Blanco, S, Cox, C, Flores, JV, Watt, S, Kudo, NR, Lyko, F & Frye, M. The mouse cytosine-5 RNA methyltransferase NSun2 is a component of the chromatoid body and required for testis differentiation. Molecular and cellular biology 33, 1561-1570, doi:10.1128/MCB.01523-12 (2013).

3   Blanco, S & Frye, M. Role of RNA methyltransferases in tissue renewal and pathology. Current opinion in cell biology 31C, 1-7, doi:10.1016/j.ceb.2014.06.006 (2014).

4   Flores, JV, Cordero-Espinoza, L, Oeztuerk-Winder, F, Andersson-Rolf, A, Selmi, T, Blanco, S, Tailor, J, Dietmann, S & Frye, M. Cytosine-5 RNA Methylation Regulates Neural Stem Cell Differentiation and Motility. Stem Cell Reports, doi:10.1016/j.stemcr.2016.11.014 (2016).

5   Blanco, S, Bandiera, R, Popis, M, Hussain, S, Lombard, P, Aleksic, J, Sajini, A, Tanna, H, Cortes-Garrido, R, Gkatza, N, Dietmann, S & Frye, M. Stem cell function and stress response are controlled by protein synthesis. Nature 534, 335-340, doi:10.1038/nature18282 (2016).

6   Martinez, FJ, Lee, JH, Lee, JE, Blanco, S, Nickerson, E, Gabriel, S, Frye, M, Al-Gazali, L & Gleeson, JG. Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome. Journal of medical genetics 49, 380-385, doi:10.1136/jmedgenet-2011-100686 (2012).

7   Hussain, S, Aleksic, J, Blanco, S, Dietmann, S & Frye, M. Characterizing 5-methylcytosine in the mammalian epitranscriptome. Genome biology 14, 215, doi:10.1186/gb4143 (2013).

8   Hussain, S, Sajini, AA, Blanco, S, Dietmann, S, Lombard, P, Sugimoto, Y, Paramor, M, Gleeson, JG, Odom, DT, Ule, J & Frye, M. NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs. Cell reports 4, 255-261, doi:10.1016/j.celrep.2013.06.029 (2013).

9   Blanco, S, Dietmann, S, Flores, JV, Hussain, S, Kutter, C, Humphreys, P, Lukk, M, Lombard, P, Treps, L, Popis, M, Kellner, S, Holter, SM, Garrett, L, Wurst, W, Becker, L, Klopstock, T, Fuchs, H, Gailus-Durner, V, Hrabe de Angelis, M, Karadottir, RT, Helm, M, Ule, J, Gleeson, JG, Odom, DT & Frye, M. Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. The EMBO journal 33, 2020-2039, doi:10.15252/embj.201489282 (2014).

10 Van Haute, L, Dietmann, S, Kremer, L, Hussain, S, Pearce, SF, Powell, CA, Rorbach, J, Lantaff, R, Blanco, S, Sauer, S, Kotzaeridou, U, Hoffmann, GF, Memari, Y, Kolb-Kokocinski, A, Durbin, R, Mayr, JA, Frye, M, Prokisch, H & Minczuk, M. Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nature communications 7, 12039, doi:10.1038/ncomms12039 (2016).

11 Frye, M & Blanco, S. Post-transcriptional modifications in development and stem cells. Development 143, 3871-3881, doi:10.1242/dev.136556 (2016).

12 Popis, MC, Blanco, S & Frye, M. Posttranscriptional methylation of transfer and ribosomal RNA in stress response pathways, cell differentiation, and cancer. Current opinion in oncology 28, 65-71, doi:10.1097/CCO.0000000000000252 (2016).

Dra. Sandra Blanco Benavente
Contacto

Centro de Investigación del Cáncer (Universidad de Salamanca-CSIC)
Campus Universitario Miguel de Unamuno s/n
37007 Salamanca
SPAIN

Líneas de investigación

Epitranscriptomics and cancer lab

 

Research interest

Our research group is interested in uncovering the molecular mechanisms regulating tissue homeostasis during normal development and during pathological conditions, in particular in cancer. Using a combination of novel transcriptome-wide analyses and mouse and human in vitro and in vivo models, we are focused on studying the role of post-transcriptional modifications such as RNA methylation in normal development and during pathological conditions.

RNA modifications are beginning to define a novel layer of biological complexity that is becoming widely appreciated as the epitranscriptome. To date over 100 known chemical modifications are known in RNA and emerging evidence is revealing that post-transcriptional modifications mediate regulation of gene expression and protein translation efficiency and accuracy. We seek to understand how RNA modifications regulate self-renewal, differentiation, growth, survival and invasion processes in normal and malignant cells.

If you are interested in working/studying in our lab, please contact Sandra Blanco. We are looking for enthusiastic and motivated PhD students and postdocs that are eligible to apply for fellowships.

Proyectos
  • (0000-0000)

    Proyecto: SAF2016-78667-R. Post-transcriptional modifications and processing of RNA in cancer stem cells

    Investigador principal: Sandra Blanco Benavente

    Entidad financiadora: Proyectos Retos i+D+i MINECO

    Periodo: 01/01/2017 - 31/12/2019

    Cantidad: 168.000 €

     

    Contrato predoctoral para formación de doctores: BES-2017-080530

    Investigador principal: Sandra Blanco Benavente

    Contratado predoctoral: Raquel García Vílchez

    Institución recetpora: Instituto de Biología Molecular y Celular del Cáncer – CSIC (Salamanca).

    Entidad financiadora: Proyectos Retos i+D+i MINECO

    Periodo: 01/09/2018 – 30/08/2021

     

     

Publicaciones

(*) Means equal contribution as senior authors.



2018
2017
2016
2014
2013
2012
2011
2012
2011
2010
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2003
Patentes
Grupo
  • Dra. Sandra Blanco Benavente Dra. Sandra Blanco Benavente

    Dra. Sandra Blanco Benavente

    Telf.:

    Fax:

    Email: sandra.blanco@usal.es


    Contacto

    Biografía

    Research during my PhD and post-doctorate period

    During my PhD and my post-doctorate, I have been engaged in finding the molecular mechanisms that lead to cancer. Initially during my PhD, at the Institute of Molecular and Cellular Biology of Cancer (Salamanca, Spain), I studied post-translation modifications (phosphorylation), and particularly dysfunctional kinases as possible targets for cancer therapy under the supervision of Prof. Pedro A. Lazo. During my post-doctorate, in the group of Dr. Michaela Frye at the Wellcome Trust – MRC Cambridge Stem Cell Institute – University of Cambridge, I studied the functional role of post-transcriptional RNA modifications in tissue homeostasis and the impact of their dysregulation in diseases such as cancer. My work largely contributed to the knowledge we have gained to date on the functional role of post-transcriptional modifications and pathological outcomes of their dysregulation, in particular 5-methylcytosine deposition in RNA. There are around 100 known covalent RNA modifications, yet our knowledge about their occurrence and physiological function in mammals is still very limited. My studies have demonstrated that cytosine-5 RNA methylation has an essential role in cellular processes including self-renewal and stress responses in tissue and cancer stem cells.

    By combining stem cell biology and mouse genetics, I found that cytosine-5 RNA methylation (m5C) is a novel mechanism by which stem and progenitor cells (both in tissue and in cancer) balance self-renewal and differentiation/proliferation properties 1-5. By using novel transcriptome‐wide sequencing approaches together with mouse genetics, I determined that cytosine-5 RNA methylation is a widespread modification in coding, non-coding RNAs and mainly transfer RNAs (tRNAs) 1,6-10 which regulated self-renewal in tissue stem cells but also sensitivity to stress in tumour initiating cells 4,5,9. Thus, my work in the laboratory of M. Frye was innovative and shed light on novel dysfunctional and targetable molecular pathways in cancer. Our findings were pioneers in exploring yet unknown mechanisms in stem cell and cancer biology and established the emergence of a novel research field coined as the Epitranscriptome. Moreover, our studies were the first to mechanistically link altered RNA methylation and cancer, and set novel road maps to chart the discovery of novel therapeutic strategies to treat cancer 5,11,12.

    After my postdoctoral position, I was awarded a Ramón y Cajal fellowship (Sept’2016) that enabled my establishment as a Junior PI at CIC bioGUNE (Spain). Since then my research has focused on epitranscriptomics in cancer, in particular defining the molecular traits that the fluctuating epitranscriptome may confer to cancer cells and cancer initiating cells.

    References

    1   Blanco, S, Kurowski, A, Nichols, J, Watt, FM, Benitah, SA & Frye, M. The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate. PLoS genetics 7, e1002403, doi:10.1371/journal.pgen.1002403 (2011).

    2   Hussain, S, Tuorto, F, Menon, S, Blanco, S, Cox, C, Flores, JV, Watt, S, Kudo, NR, Lyko, F & Frye, M. The mouse cytosine-5 RNA methyltransferase NSun2 is a component of the chromatoid body and required for testis differentiation. Molecular and cellular biology 33, 1561-1570, doi:10.1128/MCB.01523-12 (2013).

    3   Blanco, S & Frye, M. Role of RNA methyltransferases in tissue renewal and pathology. Current opinion in cell biology 31C, 1-7, doi:10.1016/j.ceb.2014.06.006 (2014).

    4   Flores, JV, Cordero-Espinoza, L, Oeztuerk-Winder, F, Andersson-Rolf, A, Selmi, T, Blanco, S, Tailor, J, Dietmann, S & Frye, M. Cytosine-5 RNA Methylation Regulates Neural Stem Cell Differentiation and Motility. Stem Cell Reports, doi:10.1016/j.stemcr.2016.11.014 (2016).

    5   Blanco, S, Bandiera, R, Popis, M, Hussain, S, Lombard, P, Aleksic, J, Sajini, A, Tanna, H, Cortes-Garrido, R, Gkatza, N, Dietmann, S & Frye, M. Stem cell function and stress response are controlled by protein synthesis. Nature 534, 335-340, doi:10.1038/nature18282 (2016).

    6   Martinez, FJ, Lee, JH, Lee, JE, Blanco, S, Nickerson, E, Gabriel, S, Frye, M, Al-Gazali, L & Gleeson, JG. Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome. Journal of medical genetics 49, 380-385, doi:10.1136/jmedgenet-2011-100686 (2012).

    7   Hussain, S, Aleksic, J, Blanco, S, Dietmann, S & Frye, M. Characterizing 5-methylcytosine in the mammalian epitranscriptome. Genome biology 14, 215, doi:10.1186/gb4143 (2013).

    8   Hussain, S, Sajini, AA, Blanco, S, Dietmann, S, Lombard, P, Sugimoto, Y, Paramor, M, Gleeson, JG, Odom, DT, Ule, J & Frye, M. NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs. Cell reports 4, 255-261, doi:10.1016/j.celrep.2013.06.029 (2013).

    9   Blanco, S, Dietmann, S, Flores, JV, Hussain, S, Kutter, C, Humphreys, P, Lukk, M, Lombard, P, Treps, L, Popis, M, Kellner, S, Holter, SM, Garrett, L, Wurst, W, Becker, L, Klopstock, T, Fuchs, H, Gailus-Durner, V, Hrabe de Angelis, M, Karadottir, RT, Helm, M, Ule, J, Gleeson, JG, Odom, DT & Frye, M. Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. The EMBO journal 33, 2020-2039, doi:10.15252/embj.201489282 (2014).

    10 Van Haute, L, Dietmann, S, Kremer, L, Hussain, S, Pearce, SF, Powell, CA, Rorbach, J, Lantaff, R, Blanco, S, Sauer, S, Kotzaeridou, U, Hoffmann, GF, Memari, Y, Kolb-Kokocinski, A, Durbin, R, Mayr, JA, Frye, M, Prokisch, H & Minczuk, M. Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nature communications 7, 12039, doi:10.1038/ncomms12039 (2016).

    11 Frye, M & Blanco, S. Post-transcriptional modifications in development and stem cells. Development 143, 3871-3881, doi:10.1242/dev.136556 (2016).

    12 Popis, MC, Blanco, S & Frye, M. Posttranscriptional methylation of transfer and ribosomal RNA in stress response pathways, cell differentiation, and cancer. Current opinion in oncology 28, 65-71, doi:10.1097/CCO.0000000000000252 (2016).

    ×
  • Víctor de Frutos Herrero Víctor de Frutos Herrero

    Víctor de Frutos Herrero

    PI3K pathway and its relationship among epitranscriptomics and cancer

    Telf.:

    Fax:

    Email: victorst98@usal.es


    Contacto

    Biografía
    -BSc Biology student at the University of Salamanca (USAL) 2016-2020.
    -Currently in the final year and doing practices at the cancer research center CIC since March 2019.

    -Interested in the pathway of PI3K and its relationship with epitranscriptomics and cancer.

    -Will start Final Year Undergrad Project on september under the supervision of Dr. Sandra Blanco at Epitranscriptomics and Cancer Lab

     

    ×
  • Raquel García Vílchez Raquel García Vílchez

    Raquel García Vílchez

    Telf.:

    Fax:

    Email: raquelgarcv@usal.es


    Contacto

    Biografía

    - PhD student in Epitranscriptomic and Cancer group, Centro de Investigación del Cáncer. FPI-2017 contract.

    - Final Master Project in Molecular Oncology Department. Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT). Madrid. Spain

    - Master degree in "Molecular and Cellular Biology". Universidad Autónoma de Madrid. 2016-2017

    - ERASMUS + Internship in Epigenetics Department in Babraham Institute. Cambridge. United Kingdom. 2016

    - Granted Internship in Instituto de Investigación Marqués de Valdecilla. Santander. Spain. 2015

    - Graduate in Biotechnology. Universidad de León. 2011-2015.

     

    Publications

    - Freire-Pritchett P, Schoenfelder S, Várnai C, Wingett SW, Cairns J, Collier AJ, García-Vílchez R, Furlan-Magaril M, Osborne CS, Fraser P, Rugg-Gunn PJ, Spivakov M. Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells. Elife. 2017 Mar 23;6. pii: e21926. doi: 10.7554/eLife.21926. PubMed PMID: 28332981; PubMed Central PMCID: PMC5407860.

     

    ×
  • Judith López Luis Judith López Luis

    Judith López Luis

    Role of ribosomal RNA methylation in prostate cancer

    Telf.:

    Fax:

    Email: judithlopezluis@hotmail.com


    Contacto

    Biografía

    - JAE intro research fellowship holder. Epitranscriptomic and Cancer Lab (2019-2020). 

    - Master degree in Biology and Clinic of Cancer by the University of Salamanca (2018-2019).

    - Collaboration Scholarship awarded by the Spanish Ministry of Education, Culture and Sport. Department of Biochemistry, Microbiology, Cell Biology and Genetics, University of La Laguna and Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC). 2017-2018. 

    - BSc Biology by the University of La Laguna (2014-2018) with Extraordinary Bachelor's Degree Award.

    ×
  • Dr. Domenico Rosace Dr. Domenico Rosace

    Dr. Domenico Rosace

    Telf.:

    Fax:

    Email: domenico.rosace@usal.es


    Contacto

    Biografía

    Realicé mis estudios de grado en "Biotecnología Médica" en la Universidad de Nápoles. Completé mi formación en biotecnología farmacéutica en la Universidad ALMA, Bolonia. En ambas Universidades adquirí un gran interés en el campo farmacéutico aplicado a la salud humana y mi voluntad de continuar mi carrera en la investigación.

    En 2013 pasé siete meses en el laboratorio de Oncología Médica de VU University Medical Center Amsterdam, donde desarrollé un proyecto de investigación en el campo de Oncología, bajo la supervisión de la Dra. Elisa Giovannetti. Esto me permitió escribir mi proyecto de tesis de maestría titulado "Role de células madre cancerosas en el comportamiento agresivo del cáncer pancreático ", supervisado por el Dr. Santi Mario Spampinato. Allí tuve la oportunidad de trabajar en un entorno internacional estimulante que adquirió un perfil internacional de alto nivel.

    Realicé mi doctorado en Inmunología y Medicina Traslacional en la Universidad de San Pablo CEU de Madrid bajo la supervisión del Dr. Domingo Barber y la Dra. Maria Marta Escribese y trabajé a mi proyecto de tesis doctoral, “Las reacciones alérgicas alimentarias mediadas por profilina están asociadas con la remodelación del epitelio oral”. Mi objetivo ha sido describir la conexión entre las alergias respiratorias y alimentarias y comprender por qué los pacientes expuestos en exceso a los alérgenos del polen de gramíneas se sensibilizaron a alérgenos alimentarios menores y algunos de ellos desarrollaron reacciones alérgicas alimentarias graves.

    Durante mi estancía en la Universidad McMaster (Ontario, Canadá), también estudié, utilizando modelos murinos, la contribución de la inmunidad de las células B IgG + y las células B de memoria en las etapas incipientes de la sensibilización epicutánea a los alimentos. He sido supervisado por el Dr. Manel Jordana y el Dr. Rodrigo Jimenez-Saiz.

    Actualmente, soy investigador postdoctoral en el laboratorio de epitranscriptómica del Centro de Investigación de Cáncer (CIC) de Salamanca. Estoy trabajando en el grupo liderado por la Dra. Sandra Blanco Benavente analizando la conexión entre las modificaciones epitranscriptómicas y el desarrollo de varios tipos de cáncer.

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  • José Antonio Sánchez Castro José Antonio Sánchez Castro

    José Antonio Sánchez Castro

    Telf.:

    Fax:

    Email: id00768224@usal.es


    Contacto

    Biografía
    ×