Jose Luis Garcia-Perez

Research interest

Transposable Elements (TEs) have been instrumental in shaping eukaryotic genomes. Notably, TEs are responsible for almost half of the human genome and although most TE insertions are “molecular fossils” which have lost the ability to mobilize, active TEs are continually impacting the human genome. Long Interspersed Element-1 (LINE-1 or L1) elements constitute 17% of our genomic mass and are a class of autonomous non-LTR retrotransposons in humans. An average human genome contains 80-100 active L1 elements capable of mobilization. Due to their random ongoing mobilization in the genome, new L1 insertions in humans can led to the appearance of sporadic cases of human genetic disorders. Indeed, L1s can impact the genome in a myriad of ways, from simply disrupting an exon to gross alterations at the insertion site. Due to their mutagenic impact on the human genome, retrotransposition is a heavily regulated process although most host factors that act to regulate retrotransposition are unknown. Thus, we are studying how host factors act to regulate retrotransposition, with a specific interest in those mechanisms that operate in our pluripotent genome to restrict retrotransposition.

Additionally, the lab is interested in understanding the functional consequences of somatic retrotransposition of LINEs in the human brain. To do that, we are using a newly develop zebrafish model that recapitulates somatic retrotransposition of LINE elements in vivo.

Publications

  • García-Pérez, J.L. , Morell, M., Scheys, J.O., Kulpa, D.A., Morell, S., Carter, C.C., Hammer, G.D., Collins, K.L., O’Shea, S., Menendez, P., and Moran, J.V.” Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells”, Nature 2010, 466(7307):769-73.

  • Macia, A., Munoz-Lopez, M., Cortes, J.L., Hastings, R., Morell, S.,Lucena-Aguilar, G., Marchal, J.A., Badge, R.M., and García-Pérez, J.L. “Epigenetic control of retrotransposon expression in human embryonic stem cells”, Mol. Cell. Biol., 2011, 31(2): 300-16.

  • Kopera, H.C., Moldovan, J.B., Morrish, T.A., García-Pérez, J.L., and Moran, J.V. “Similarities between the mechanisms of endonuclease independent LINE-1 retrotransposition and telomerase”, Proc Natl Acad Sci U S A. 2011 Dec 20; 108(51):20345-50. Epub 2011 Sep 22.

  • Shukla, R., Upton, K., Muñoz-Lopez, M., Gerhardt, D.J., Fisher, M.E., Nguyen, T., Baillie, J.K., Brennan, P.M. Collino, A., Ghisletti, S., Sinha, S., Iannelli, F., Radaelli, R., Dos Santos, A., Rapoud, D., Guettier, C., Samuel, D., Natoli, G., Carninci, P., Ciccarelli, F.D., García-Pérez, J.L., Faivre, J., and Faulkner, G.J. “Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma”. Cell 2013, Mar 28;153(1):101-11. doi: 10.1016/j.cell.2013.02.032.

  • Heras SR, Macias S, Plass M, Fernandez N, Cano D, Eyras E, Garcia-Perez JL.1 , Cáceres JF. “The Microprocessor controls the activity of mammalian retrotransposons” Nature Struct Mol Biol. 2013 Oct;20(10):1173-81. doi: 10.1038/nsmb.2658. Epub 2013 Sep 1.

  • Klawitter S*, Fuchs NV*, Upton KR*, Muñoz-Lopez M*, Shukla R, Wang J, Garcia-Cañadas M, Lopez-Ruiz C, Gerhardt DJ, Sebe A, Grabundzija I, Merkert S, Gerdes P, Pulgarin JA, Bock A, Held U, Witthuhn A, Haase A, Sarkadi B, Löwer J, Wolvetang EJ, Martin U, Ivics Z, Izsvák Z, Garcia-Perez JL1, Faulkner GJ, Schumann GG. “Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells” Nature Commun. 2016 Jan 8;7:10286. doi: 10.1038/ncomms10286.

  • García-Pérez, J.L., Widmann, T.J., Adams, I.R. “The Impact of transposable elements on mammalian development”, Development, 2016, Nov 15;143(22):4101-4114.

  • Angela Macia, Thomas J. Widmann Sara R. Heras, Veronica Ayllon, Laura Sanchez, Meriem Benkaddour-Boumzaouad, Martin Muñoz-Lopez, Suyapa Amador-Cubero, Eva Blanco-Jimenez, Javier Garcia-Castro, Pablo Menendez, Philip Ng, Alysson R. Muotri, John L. Goodier7 and García-Pérez, J.L. “Engineered LINE-1 retrotransposition in non-dividing human neurons” Genome Research, 2016, in press.

Active Grants

    Title: Biology of LINE-1 retrotransposons
    Funded by: Howard Hughes Medical Institute, Early Career International Program
    Budget: 715.000 $ (USD)
    Expedient: IECS-55007420
    Dates: 01/02/12 – 31/01/17 (60 months)
    Principal Investigator: Jose Luis Garcia-Perez

    Title: EPIPLURIRETRO: Epigenetic control and impact of mammalian retrotransposons in pluripotent genomes.
    Expedient: ERC-STG-2012-233764
    Funded by: European Research Council (ERC-Consolidator Grants).
    Budget: 1.483.000 €
    Dates: 01/07/13 – 31/06/18 (60 months)
    Principal Investigator: Jose Luis Garcia-Perez

    Title: EVOLINE: Mobile elements: shuffling the regulome indevelopment and disease.
    Expedient: FP7-PEOPLE-2013-IOF-623324
    Funded by: Marie Curie Actions, International Outgoing Fellowship, EU.
    Budget: 265.317 €
    Dates: 01/02/15 – 31/01/18 (36 months)
    Principal Investigator: Francisco Sánchez Luque.

    Title: Elementos LINE como mediadores de variación genómica somática: desarrollo de un modelo de Zebrafish.
    Funded by: Consejería de Innovación, Ciencia y Empresa de la Junta de Andalucía (Proyectos de Excelencia calidad Motriz).
    Expedient: P12-CTS-2256
    Budget: 177.750 €
    Dates: 01/06/14 – 31/05/18 (48 months)
    Principal Investigator: Jose Luis Garcia-Perez

    Title: Papel del retroelemento humano LINE-1 en la patogénesis de enfermedades raras asociadas con la reparación del DNA humano.
    Expedient: FISPI14/02152
    Funded by: Instituto de Salud Carlos III (Proyectos de Investigación en Salud)
    Budget: 98.615 €
    Dates: 01/01/15 – 31/12/17 (36 months)
    Principal Investigator: Jose Luis Garcia-Perez

    Title: Estudio de las bases moleculares de la interfernopatia tipo I por Neuroinflamacion en el síndrome de Aicardi-Goutieres (AGS).
    Expedient: PCIN-2014-115
    Funded by: ERA-NET NEURON II (Ministerio de Economia y Competitividad)
    Budget: 150.000 €
    Dates: 15/01/15 – 14/01/18 (36 months)
    Principal Investigator: Jose Luis Garcia-Perez

    Title: Papel de la movilidad de LINE-1 en la resistencia a cancer.
    Funded by: Consejería de Salud de la Junta de Andalucía (Proyectos de investigación).
    Budget: 33.698 €
    Expedient:: PI-0022-2014
    Dates: 01/06/15 – 31/05/17
    Principal Investigator: Martin Muñoz-Lopez.

    Title: Papel de microRNAs en el control de la movilidad y en el impacto del retrotransposon humano LINE-1 en tumores.
    Expedient: SAF2015-71589-P
    Funded by: MINECO (Ministerio de Economia y Competitividad)
    Budget: 147.000€
    Dates: 01/01/16 – 30/12/18 (36 months)
    Principal Investigator: Sara Rodriguez Heras

    Title: Papel del retroelemento L1 en la patogénesis de enfermedades raras asociadas con la reparación del DNA humano: Anemia de Fanconi y Síndrome de Aicardi–Goutières
    Funded by: Consejería de Salud de la Junta de Andalucía (Proyectos de investigación).
    Budget: 57.084 €
    Expedient: PI-0059-2016
    Dates: 01/06/17 – 31/05/19
    Principal Investigator: Ana Ariza.

Group members

Group Leader
  • Jose Luis Garcia-Perez, PhD
Post-doctoral fellows
  • Martin Muñoz-Lopez, PhD
  • Marta Garcia-Cañadas, PhD
  • Sara Rodriguez Heras, PhD
  • Thomas Widmann, PhD
  • Francisco Jose Sanchez Luque, PhD
PhD students
  • Juan David Cano Martinez
  • Meriem Benkaddour
  • Pablo Tristan Ramos
  • Maria Benitez Guijarro
Technicians
  • Laura Sanchez
  • Raquel Vilar Astasio
  • Maria Esther Prada Sanchez