Dr Paloma Garcia PhD

Dr Paloma Garcia

Institute of Cancer and Genomic Sciences
Senior Research Fellow

Contact details

Telephone
+44 (0)121 414 4093
Email
p.garcia@bham.ac.uk
Twitter
@PgGarcialab
View my research portal
Address
Institute of Biomedical Research
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

The Garcia group research interest is to understand the molecular mechanisms that maintain genome integrity in stem cells and how loss of genome integrity leads to development of cancer during ageing. Her research focus on both embryonic stem cells ESC/iPSC and adult stem cells, in particular haemopoietic stem cells and breast cancer initiating cells.

Qualifications

Principal Investigator in Stem cells and genome stability:

  • PhD (1997) Medical School, Universidad Autónoma of Madrid
  • BSc Biology (1994) School of Biology, Universidad Autónoma of Madrid

Biography

Paloma Garcia studied Biology at the Universidad Autonoma of Madrid, Spain and joined the lab of Professor Carmela Cales at the School of Medicine (Universidad Autonoma, Madrid) for a PhD project studying the molecular mechanisms leading to the establishment of endoreplicative cycles in megakaryocytes (1994-1997). During this period Paloma was awarded an EMBO short term fellowship to perform some of these studies at the Weatherall Institute of Molecular Medicine (WIMM), Oxford, under the supervision of Professor Jon Frampton. 

Following her PhD work, Paloma was awarded a Marie Curie fellowship to join Professor Frampton lab in WIMM, Oxford, where she established a conditional gene deletion approach to investigate MybL2 function and started working on stem/progenitor cell properties and the development of blood disorders. 

In 2002 she moved to University of Birmingham as a senior postdoctoral researcher funded through the Leukaemia and Lymphoma Research (LLR). She was able to demonstrate that correct levels of MybL2 are necessary to maintain genome stability in human haemopoietic cells, and that low levels result in DNA fragmentation and chromosome rearrangements. 

García’s independent research group was established in 2009, once she was awarded a Researcher Fellow position at the University of Birmingham through the Science City Research Alliance scheme (SCRA). Using her mouse model, she demonstrated the importance of MybL2 in the development of blood disorders during ageing. She also led the investigation that revealed a role for MybL2 in the elongation rate of replication forks in ESC.

She now holds a Senior Researcher position at the University of Birmingham

Teaching

Undergraduate

Masters

Postgraduate supervision

Dr Paloma Garcia is interested in supervising doctoral research students in the following areas:

* molecular mechanisms controlling genome stability in embryonic stem cells and induced pluripotent stem cells

* molecular mechanisms of somatic reprogramming to induced pluripotent stem cells

* molecular mechanisms underlying blood disorders during ageing.

Self-funded PhD students are welcome to apply.

Research

  • iPSC as disease modelling system to understand MDS progression and therapy resistance.
  • MYBL2 in Breast cancer stem/initiating cells. 
  • Mechanisms regulating proliferation and genomic stability in embryonic stem cells and somatic cells, with a special focus into the role of the transcription factor MybL2 (B-Myb) at the interplay between DNA replication and DNA repair.
  • Investigation of the molecular basis behind the deletion of chromosome 20q (del20q), and in particular the role of MybL2 haploinsufficiency in the development of haematological diseases.

Birmingham University Stem Cell Centre (BUSCC)

Collaborators


Other activities

Paloma is a Member of the Mercia Stem Cell Alliance (MSCA) and Birmingham University Stem Cell Centre (BUSCC).

She acts as a reviewer for grant funding bodies and journals.

Publications

Blakemore, D., Vilaplana-Lopera, N., Almaghrabi, R.,…. and García, P*. (2021)  MYBL2 and ATM suppress replication stress in pluripotent stem cells. EMBO Reports. DOI: 10.15252/embr.202051120

Jianming Wang, Patricia Rojas, Jingwen Mao, Ho Leung, Martin Higgs, Paloma Garcia, Marco Saponaro. (2021). Persistence of RNA transcription at transcription start sites during DNA replication induces G2/M DNA synthesis Cell Reports.https://doi.org/10.1016/j.celrep.2021.108759

Gleneadie HJ, Baker A, Batis N, Bryant J, Jiang Y, Clokie SJH, Mehanna H, Garcia P, Gendoo DMA, Roberts S, Molinolo AA, Gutkind JS, Scheven BA, Cooper PR, Khanim FL, Wiench M. (2021) A common analgesic enhances the anti-tumour activity of 5-aza-2’-deoxycytidine through induction of oxidative stress  Cancer Letters. doi: 10.1016/j.canlet.2020.12.029.

Bayley,R., Ward, C., and García, P*. (2020) MYBL2 Amplification in Breast Cancer: Molecular Mechanisms and Therapeutic Potential. BBA:Reviews on Cancer. DOI: 10.1016/j.bbcan.2020.188407

Muñoa‑Hoyos, I., Halsall, J.A., Araolaza, M., Ward, C., Garcia, I., Urizar‑Arenaza, I., Gianzo, M., García, P., Turner, ., and Subirán, N. (2020) Morphine leads to global genome changes in H3K27me3 levels via a Polycomb Repressive Complex 2 (PRC2) self‑regulatory mechanism in mESCs. Clin Epigenet 12:170. https://doi.org/10.1186/s13148-020-00955-w

Ward, C., Volpe, G., Ptasinska, A., Nafria Fedi, Cauchy, P., M., Frampton, K., Murphy, G., Buganim, Y., Kaji, K., and García, P*. (2018) Fine-tuning Mybl2 is required for proper mesenchymal-to-epithelial transition during somatic reprogramming. Cell Reports 24 (6): 1496-1511. DOI:10.1016/j.celrep.2018.07.026.

Bayley, R., Blakemore, D., Cancian, L., Dumon, S., Volpe, G., Ward, C., AlMaghrabi, R., Gujar, J., Reeve, N., Raghavan, M., Stewart, G., Higgs, M., Petermann, E., and García, P*. (2018) MYBL2 supports DNA double strand break repair in Haematopoietic Stem Cells. Cancer Research DOI: 10.1158/0008-5472.CAN-18-0273. 

Volpe, G., Walton, D. S., Grainger, D.E., Ward, C., Cauchy, P., Blakemore, D., Coleman, D.J.L., Cockerill, P.N., García, P*., Frampton, J*. (2017) Prognostic significance of high GFI1expressionin AML of normal karyotype and its association with a FLT3-ITD signature. Scientific Reports, 7. DOI:10.1038/s41598-017-11718-8. 

Clarke, M. L., Volpe, G., Sheriff, L., Walton, D., Ward, C., Wei, W., Dumon, S., García, P* and Frampton, J*. (2017) Transcriptional regulation of SPROUTY 2 and DUSP6 by MYB influences myeloid cell proliferation and stem cell properties by enhancing responsiveness to IL-3. Leukaemia  Apr; 31(4): 957–966. DOI: 10.1038/leu.2016.289  

Iltzsche, F., Simon, K., Stopp, S., Pattschull, G., Francke, S., Wolter, P., Hauser, S., Murphy, D.,  García, P, Rosenwald, A., and Gaubatz, S. (2017) An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma. Oncogene 36:110-121  DOI:10.1038/onc.2016.181

Volpe, G., Clarke,M.L., García, P., Walton, D. S.,et al. (2015) Regulation of the Flt3 Gene in Haematopoietic Stem and Early Progenitor Cells. PLOS One. DOI: 10.1371/journal.pone.0138257

Dolz, S., García, P., Llop, M., Fuster, O.,et al. (2015) Study of the S427G polymorphism and of MYBL2variants in patients with acute myeloid leukemia. Leukaemia & Lymphoma. DOI:10.3109/10428194.2015.1049167 

Sakamoto, H., Takeda, N., Arai, F., Hosokawa, K., García, P., Suda, T., Frampton, J., and Ogawa, M. (2015). Determining c-Myb Protein Levels Can Isolate Functional Hematopoietic Stem Cell Subtypes Stem Cells, 33 (2): 479-490. 

Fuster, O., Llop, M., Dolz, S., García, P., Such, E.,et al. (2013)  Adverse prognostic value of MYBL2 overexpression and association with microRNA-30 family in acute myeloid leukemia patients. Leukaemia Research, 37 (12): 1690-6. 

Volpe, G., Walton, D. S., Del Pozzo, W., García, P., Dasse, E., O'Neill, L., Griffiths, M., Frampton, J., and Dumon, S. (2013) C/EBPa and MYB regulate FLT3 expression in AML. Leukaemia, 27:1487-96.

Clarke, M.L., Dumon, S., Ward, C., Jager, R., Freeman, S., Dawood, B., Sheriff, L., Lorvellec, M., Kralovics, R., Frampton, J and García, P*. (2013) MybL2 haploinsufficiency increases susceptibility to age-related haemopoietic neoplasia. Leukaemia, 27: 661–670. 

Jones, R.M., Mortusewicz,O., Afzal, I., Lorvellec, M., García, P., Helleday, T and Petermann, E.(2013) Oncogene-induced replication stress by increased replication initiation resulting in conflicts with transcription. Oncogene, 32: 3744-53.

Haining, E.J., Yang, J., Bailey,R. L., Khan, K., Collier, R., Tsai, S., Watson,S.P., Frampton, J., García, P., Tomlinson M. (2012) The TspanC8 Subgroup of Tetraspanins Interacts with A Disintegrin and Metalloprotease 10 (ADAM10) and Regulates Its Maturation and Cell Surface Expression. J Biol Chem, 287(47): 39753-65. 

García, P*., Berlanga, O., Vegiopoulos, A., Vyas, P and Frampton, J. (2011). c-Myb and GATA-1 alternate dominant roles during megakaryocyte differentiation. J Thromb Haemost, 9(8):1572-1581.

Lorvellec, M., Dumon, S., Maya-Mendoza, A., Jackson, D., Frampton, J., and García, P*. (2010). B-Myb is Critical for Proper DNA Duplication during an Unperturbed S phase in Mouse Embryonic Stem Cells. Stem Cells, 28: 1751-1759.

García, P*. Clarke, M.L., Vegiopoulos, A., Berlanga, O., Camelo, A., Lorvellec, M. and Frampton, J. (2009) Reduced c-Myb activity compromises HSCs and leads to a myeloproliferation with a novel stem cell basis. EMBO J, 28: 1492-1504.

García P., and Frampton, J. (2008) Hematopoietic lineage commitment: miRNAs add specificity to a widely expressed transcription factor. Dev Cell. 14: 815-6.

García, P., and Frampton J. (2006). The transcription factor B-Myb is a key regulator of DNA replication in both diploid and polyploidy megakaryocytes. J Cell Sci, 119: 1483-93.

Vegiopoulos, A., García, P., Emambokus, N. and Frampton, J. (2006) Coordination of erythropoiesis by the transcription factor c-Myb. Blood, 107: 4703-10.

García, P., Berlanga, O., Watson, R., and Frampton J. (2005) Generation of a conditional allele of the B-Myb gene. Genesis, 43: 189-95.

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