CENTRO DE INVESTIGACION DEL CANCER

  • Laboratorio 5 - Sandra

Dra. Sandra Blanco Benavente


Biography

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
Contact

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

Areas of Research

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.

Projects
  • (0000-0000)

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

    Principal Investigator: Sandra Blanco Benavente

    Funding body: Proyectos Retos i+D+i MINECO

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

    Amount: 168.000 €

     

    PhD fellowship: BES-2017-080530

    Principal Investigator:  Sandra Blanco Benavente

    PhD student: Raquel García Vílchez

    Funding body: Proyectos Retos i+D+i MINECO

    Period: 01/09/2018 – 30/08/2021

  • (0000-0000)

    FS/21-2018: Alteraciones de los patrones de metilación citosina-5 de ARN en cáncer de próstata

    Principal investigator: Sandra Blanco Benavente

    Receiving Institution: Instituto de Biología Molecular y Celular del Cáncer – CSIC - USAL

    Financial entity/programme: Ayudas a la investigación fundación memoria de Samuel Solorzano Barruso

    Duration: 01/01/2019 - 31/12/2019

    Amount: 1473€

     

    LABAE19040BLAN: Post-transcriptionally modified RNAs as regulators of growth and survival in cancer.

    Principal investigator: Sandra Blanco Benavente

    Receiving Institution: Instituto de Biología Molecular y Celular del Cáncer – CSIC - USAL

    Financial entity/programme: Scientific Foundation AECC

    Duration: 01/01/2020 - 31/12/2022

    Amount: 300.000 €

Publications

(*) Means equal contribution as senior authors.



2021
2020
2019

Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program.

Janin M, Ortiz-Barahona V, de Moura MC, Martínez-Cardús A, Llinàs-Arias P, Soler M, Nachmani D, Pelletier J, Schumann U, Calleja-Cervantes ME, Moran S, Guil S, Bueno-Costa A, Piñeyro D, Perez-Salvia M, Rosselló-Tortella M, Piqué L, Bech-Serra JJ, De La Torre C, Vidal A, Martínez-Iniesta M, Martín-Tejera JF, Villanueva A, Arias A, Cuartas I, Aransay AM, La Madrid AM, Carcaboso AM, Santa-Maria V, Mora J, Fernandez AF, Fraga MF, Aldecoa I, Pedrosa L, Graus F, Vidal N, Martínez-Soler F, Tortosa A, Carrato C, Balañá C, Boudreau MW, Hergenrother PJ, Kötter P, Entian KD, Hench J, Frank S, Mansouri S, Zadeh G, Dans PD, Orozco M, Thomas G, Blanco S, Seoane J, Preiss T, Pandolfi PP, Esteller M, 
Acta Neuropathol.; 2019; 138(6); 1053-107; 31428936


2018
2017
2016
2014
2013
2012
2011
2010
2009
2008
2007
2006
2004
2003
Patents
Group
  • Ana Macrina Añazco Guenkova Ana Macrina Añazco Guenkova

    Ana Macrina Añazco Guenkova

    Telf.:

    Fax:

    Email: ana.anazco@usal.es


    Contact

    Biography

    - BSc Biology by the University of Alcalá, Madrid (2015-2019) 

    -Final Year Undergrad Project and practices in the Molecular Genetics field (2019) 

    -Currently studying for a Master’s degree in Biology and Clinic of Cancer by the University of Salamanca (2019-2020).

    -During my Master’s, I am doing my Practicum in the CIC laboratory of Epitranscriptomics and Cancer, focusing on the functional role of RNA modifications in the activation and maturation of immune cells (2019-2020)

    ×
  • Dra. Sandra Blanco Benavente Dra. Sandra Blanco Benavente

    Dra. Sandra Blanco Benavente

    Telf.:

    Fax:

    Email: sandra.blanco@usal.es


    Contact

    Biography

    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).

    ×
  • Alba Cisneros Martín Alba Cisneros Martín

    Alba Cisneros Martín

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    Email: alba.cisneros42@gmail.com


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    ×
  • Raquel García Vílchez Raquel García Vílchez

    Raquel García Vílchez

    Epitranscriptomics in prostate cancer

    Telf.:

    Fax:

    Email: raquelgarcv@usal.es


    Contact

    Biography

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

    - Master degree in "Mollecular and Cell 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.

    ×
  • Judith López Luís Judith López Luís

    Judith López Luís

    Role of ribosomal RNA methylation in prostate cancer

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    Email: judithlopezluis@hotmail.com


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    Biography

    - University Professor Training Program (FPU) Fellow (2020-2023)

    - AECC predoctoral Fellow (2019-2020)

    - PhD Student at Epitranscriptomics and Cancer Lab under the supervision of Dr Sandra Blanco (2019-).

    - JAE intro Research Fellow. Epitranscriptomic and Cancer Lab (Oct 2019-Nov 2019). 

    - Master's degree in Biology and Clinic of Cancer by the University of Salamanca (2018-2019)  with Extraordinary Master's Degree Award. 

    - 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 End-of-Degree Award.

    ×
  • Borja Miguel López Borja Miguel López

    Borja Miguel López

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    Email: borja_miguel@usal.es


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  • Óscar Monteagudo García Óscar Monteagudo García

    Óscar Monteagudo García

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    Email: oscar.4mg@gmail.com


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  • Mª Paz Nombela Blanco Mª Paz Nombela Blanco

    Mª Paz Nombela Blanco

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    Email: mpnombela@usal.es


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  • Domenico  Rosace Domenico Rosace

    Domenico Rosace

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    Email: domenico.rosace@usal.es


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    Biography

    I carried out my Bechelor studies in "Medical Biotechnology" in the University of Naples. I completed my training in Pharmaceutical Biotechnology in ALMA University, Bologna. In both Universities I acquired my strong interest in pharmacheutical field applied to human health and my will to prosecute my career on research.

    In 2013 I spent seven months in the laboratory of Medical Oncology of VU University Medical Center Amsterdam where I developed a research project in the Oncology field, under the supervision of Dr. Elisa Giovannetti.This allowed me to write my Master thesis project entitled "Role of Cancer Stem Cells in the aggressive behaviour of Pancreatic Cancer", supervised by Dr. Santi Mario Spampinato.There I had the opportunity to work in a stimulating international enviroment acquiring a high-level international profile.

    I performed my PhD in Immunology and translational Medicine in San Pablo CEU University of Madrid under the co-supervision of Dr. Domingo Barber and Dra. Maria Marta Escribese and I worked on my PhD thesis project, “Profilin-mediated food allergic reactions are associated with oral epithelial remodeling”. I aimed to describe the connection among respiratory and food allergy and understand why patients overexposed to grass pollen allergens became sensitized to minor allergens and some of them developed severe food allergic reactions.

    During my stay in McMaster University (Ontario Canada), I also studied, using murine models, the contribution of IgG+ B cell immunity and B memory cells in the incipient stages of epicutaneous sensitization to foods. I have been supervised by Dr. Manel Jordana and Dr. Rodrigo Jimenez-Saiz.

    Currently, I am a postdoctoral researcher in the epitranscriptomic laboratory of the Cancer reasearch Center (Centro de Investigación del Cáncer CIC) of Salamanca. I am working in the group leadered for DR. Sandra Blanco Benavente analyzing the connection between epitranscriptomic modification and cancer development.

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  • José Antonio Sánchez Castro José Antonio Sánchez Castro

    José Antonio Sánchez Castro

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    Email: id00768224@usal.es


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Formers Members
  • Víctor  de Frutos Herrero Víctor de Frutos Herrero

    Víctor de Frutos Herrero

    PI3K pathway and its relationship among epitranscriptomics and cancer

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    Email: victorst98@usal.es


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    -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 -September 2020: Master de biología y tecnología aplicada a la reproducción humana asistida en la Universidad de Europa.

     

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  • Virginia   Moron Calvente Virginia Moron Calvente

    Virginia Moron Calvente

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    Email: nix_bio@usal.es


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