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Mario Capecchi

Distinguished Professor of Human Genetics and
Professor of Biology and
Adjunct Professor of Oncological SciencesMario Capecchi

2007 Nobel Prize Winner for Physiology or Medicine

B.S. Antioch College

Ph.D. Harvard University

Research

References

Mario Capecchi's Lab Page

Mario Capecchi's PubMed Literature Search

Molecular Biology Program

Mammalian Development, Human Pathology from Cancer to Neuropschiatric Disorders

Research

Our research efforts are directed towards the analysis of the developmental programs mediating pattern formation, organogenesis and neurogenesis in the mouse. Towards achieving these goals, we have pioneered the technology required for generating mutations in any gene in the mouse. This technology employs the exchange of DNA sequences, by homologous recombination, between exogenous, newly added DNA sequences and the cognate chromosomal DNA sequences in embryo-derived mouse stem (ES) cells. This process is referred to as "gene-targeting." The ES cells containing the desired targeting event are then used to generate mouse germ line chimeras, capable of transmitting the mutation to their progeny.

We are using this technology to determine the function of genes believed to mediate important developmental decisions in the mouse embryo. This technology is also being used to generate mouse models for human genetic diseases from cancer to neuropsychiatric disorders . Such animals allow a deeper analysis of the pathogenesis of the human disease, as well as provide appropriate subjects for testing new therapeutic protocols including somatic gene therapy. Eventually, this technology should also provide an avenue for directly correcting genetic defects in humans via somatic gene therapy.

References

  1. Jones, K.B., Barrott, J.J., Haldar, M., Jin, H., Zhu, J.F., Monument, M., Langer, E., Randall, R.L. and M.R. Capecchi (2016). The impact of chromosomal translocation locus and fusion oncogene coding sequence in synovial sarcomagenesis. Oncogene. 2016 Mar 7.
  2. Carroll, L.S. and Capecchi, M.R. (2015). HOXC8 initiates an ectopic mammary program by regulating Fgf10 and Tbx3 expression, and Wnt/β-catenin signaling. Development.142(23):4056-67.
  3. Prigge, J.R., Hoyt, T.R., Dobrinen, E., Capecchi, M.R., Schmidt, E.E., N. Meissner (2015). Type I IFNs Act upon Hematopoietic Progenitors to Protect and Maintain Hematopoiesis during Pneumocystis Lung Infection in Mice. J Immunol. 195(11):5347-57.
  4. Pozner, A. and Capecchi, M. (2015). ASPM regulates symmetric stem cell division by tuning Cyclin E ubiquitination. Nature Communications.6:8763.
  5. Roux, M., Laforest, B., Capecchi, M., Bertrand, N., S. Zaffran (2015). Hoxb1 regulates proliferation and differentiation of second heart field progenitors in pharyngeal mesoderm and genetically interacts with Hoxa1 during cardiac outflow tract development. Dev Biol.406:2:247-58.
  6. Quist, T., Jin, H., Zhu, J., Smith-Fry, K., Capecchi, M.R. and K.B. Jones (2014). The impact of osteoblastic differentiation on osteosarcomagenesis in the mouse. Oncogene. 34(32):4278-84.
  7. Pozner, A., Xu, B., Palumbos, S., Gee, J.M., Tvrdik, P., M.R. Capecchi (2015). Intracellular calcium dynamics in cortical microglia responding to focal laser injury in the PC::G5-tdT reporter mouse. Front Mol Neurosci.8:12.
  8. Gee, J.M., Gibbons, M.B., Taheri, M., Palumbos, S., Morris, S.C., Smeal, R.M., Flynn, K.F., Economo, M.N., Cizek, C.G., Capecchi, M.R., Tvrdik, P., Wilcox, K.S., J.A. White (2015). Imaging activity in astrocytes and neurons with genetically encoded calcium indicators following in utero electroporation. Front Mol Neurosci.8:10. eCollection 2015.
  9. Goodwin, M.L., Jin, H., Straessler, K., Smith-Fry, K., Zhu, J.F., Monument, M.J., Grossmann. A., Randall, R.L., Capecchi, M.R. and K.B. Jones (2014). Modeling alveolar soft part sarcomagenesis in the mouse: a role for lactate in the tumor microenvironment. Cancer Cell. 26(6):851-62.
  10. Haldar, M., Karan, G., Watanabe, S., Guenther, S. Braun, T. and M.R. Capecchi (2014). Responses: contributions of the myf5-independent lineage to myogenesis. Dev. Cell31(5) 539-41.
  11. Chojnowski, J.L., Masuda, K., Trau, H.A. Thomas, K., Capecchi, M.R. and N. R. Manley (2014). Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis. Dev.141:3697-3708.
  12. Gee, J.M., Smith, N.A., Fernandez, F.R., Economo, M.N., Brunert, D., Rothermel, M. Morris, S.C., Talbot, A. Palumbos, S., Ichida, J., Shepherd, J., West, P.J., Wachowiak, D.M., Capecchi, M.R., Wilcox, K. S. White, J. A., Tvrdik, P. (2014). Imaging Activity in Neurons and Glia with a Polr2a-based and Cre-dependent GCaMP5G-IRES-tdTomato Reporter Mouse. Neuron.83:1058-72.
  13. Wu, S., Y. Wu, X. Zhang, and M.R. Capecchi (2014). Efficient germ-line transmission obtained with transgene-free induced pluripotent stem cells. Proc Natl Acad Sci U S A.111(29):10678-83.
  14. Abraham, J., Nunez-Alvarez, Y., Hettmer, S., Carrio, E., Chen, H., Nishijo, K., Huang, E.T., Prajapati, S., Walker, R.L., Davis, S., Rebeles, J., Wiebush, H., McCleish, A.T., Hampton, S.T., Bjornson, C.R.R., Brack, A.S., Wagers, A.J., Rando, T.A., Capecchi, M.R., Marini, F.C., Ehler, B.R., Zarzabal, L.A., Goros, M.W., Michalek, J.E., Meltzer, P.S., Langenau, D.M., LeGallo, R.D., Mansoor, A., Chen, Y., Suelves, M., Rubin, B.P. and C. Keller (2014). Lineage of origin in rhabdomyosarcoma informs pharmacological response. Gen Dev.28:1578-1591.
  15. Kurokawa, S., S. Eriksson, K.L. Rose, S. Wu, A.K. Motley, S. Hill, V.P. Winfrey, W.H. McDonald, M.R. Capecchi, J.F. Atkins, E.S. Arnér, K.E. Hill, and R.F. Burk (2014). Sepp1(UF) forms are N-terminal selenoprotein P truncations that have peroxidase activity when coupled with thioredoxin reductase-1. Free Radic Biol Med.69:67-76.
  16. Jones, K.B., L. Su, H. Jin, C. Lenz, R.L. Randall, T.M. Underhill, T.O. Nielson, S. Sharma, and M.R. Capecchi (2013). SS18-SSX2 and the mitochondrial apoptosis pathway in mouse and human synovial sarcomas. Oncogene. 32(18):2365-71, 2375.e1-5.
  17. Straessler, K.M., K.B. Jones, H. Hu, H. Jin, M. van de Rijn, and M.R. Capecchi (2013). Modeling clear cell sarcomagenesis in the mouse: cell of origin differentiation state impacts tumor characteristics. Cancer Cell.23(2):215-27.
  18. Boulet, A.M. and M.R. Capecchi (2012). Signaling by FGF4 and FGF8 is required for axial elongation of the mouse embryo. Dev Biol.371(2):235-45.
  19. Makki, N. and M.R. Capecchi (2012). Cardiovascular defects in a mouse model of HOXA1 syndrome. Hum. Mol. Genet.21(91):26-31.
  20. Makki, N. and M.R. Capecchi (2011). Identification of novel Hoxa1 downstream targets regulating hindbrain, neural crest and inner ear development. Dev. Bio. 357(2):295-304.
  21. Makki, N. and M. R. Capecchi (2010). Hoxa1 linage-tracing indictes a direct role for Hoxa1 in development of the inner ear, the heart and the third rhombomere. Dev Bio.341(2):499–509.
  22. Xue, H., S. Wu, S.T. Papadeau, S. Spusta, A.M. Swistowska, C.C. MacArthur, M.P. Mattson, N.J. Maragakis, M.R. Capecchi, M.S. Rao, S. Zeng, and Y. Liu (2009). A targeted neuroglial reporter line generated by homologous recombination in human embryonic stem cells. Stem Cell.27(8): 1836-46.
  23. Haldar, M., M. Hedberg, M. Hockin, and M.R. Capecchi (2009). A CreER based random induction strategy for modeling translocation-associated sarcomas in mice. Cancer Res.69(8):3657-64.
  24. Sangiorgi, E. and M.R. Capecchi (2008). Bmi1 lineage tracing identifies a self-renewing pancreatic acinar cell subpopulation capable of maintaining pancreatic organ homeostasis. PNAS.106(17):7101-7106.
  25. Ray, R. and M.R. Capecchi (2008). An examination of the chiropteran HoxD locus from an evolutionary perspective. Evol. & Dev.10(6):657-70.
  26. Sangiorgi, E., Z. Shuhua, and M.R. Capecchi (2008). In vivo evaluation of PhiC31 recombinase activity using a self-excision cassette. Nucleic Acids Res.36(20):e134.
  27. Capecchi, M.R. (2008). The Making of a Scientist II (Nobel Lecture). ChemBioChem9(10):1530-43.
  28. Sangiorgi, E. and M.R. Capecchi (2008). Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet. 40(7):915-20.
  29. Haldar, M., R.L. Randall, and M. R. Capecchi (2008). Synovial Sarcoma: From Genetics to Genetic-based Animal Modeling. Clin OrthopRelat Res.466(9):2156-67.
  30. Haldar, M. G. Karan, P. Tvrdik, and M.R. Capecchi (2008). Two cell lineages, Myf5-independent, participate in mouse skeletal myogenesis. Dev Cell.14(3):437-45.
  31. Wu, S., G. Ying, Q. Wu, and M.R. Capecchi (2008). A protocol for constructing gene targeting vectors: generating knockout mice for the cadherin family and beyond. Nat Protocols. 3(6):1056-76.
  32. Vasquez, S.X., M.S. Hansen, A.N. Bahadur, M.F. Hockin, G.L. Kindlmann, L. Nevell, I.Q. Wu, D.J. Grunwald, D.M. Weinstein, G.M. Jones, C.R. Johnson, J.L. Vandeberg, M.R. Capecchi, and C. Keller (2008). Optimization of volumetric computed tomography for skeletal analysis of model genetic organisms. Anat Rec. 291(5):475-487.
  33. Wu, Y., G. Wang, S.A. Scott, and M.R. Capecchi (2008). Hoxc10 and Hoxd10 regulate mouse columnar, divisional, and motor pool identity of lumbar motoneurons. Development.135(1):171-182.
  34. Bondareva, A.A., M.R. Capecchi, S.V. Iverson, Y. Li, N.I. Lopez, O. Lucas, G.F. Merrill, J.R. Prigge, A.M. Siders, M. Wakamiya, S.L. Wallin, and E.E. Schmid (2007). Effects of thioredoxin reductase-1 deletion on embryogenesis and transcriptome. Free Radic Biol Med.43(6):911-23.
  35. Barrow, J.R., W.D. Howell, M. Rule, S. Hayashi, K.R. Thomas, M.R. Capecchi, and A.P. McMahon (2007). Wnt3 signaling in the epiblast is required for proper orientation of the anteroposterior axis. Dev. Biol. 312(1):312-20.
  36. McIntyre, D.C., S. Rakshit, A.R. Yallowitz, L. Loken, L. Jeannotte, M.R. Capecchi, and D.M. Wellik (2007). Hox patterning of the vertebrate rib cage. Development.134(16):2981-9.
  37. Wu, S., G. Ying, Q. Wu, and M.R. Capecchi (2007). Towards simpler and faster genome-wide mutagenesis in mice. Nat Genet. 39(7):922-30.
  38. Shen, X.Z., P. Li, D. Weiss, S. Fuchs, H.D. Xiao, J.A. Adams, I.R. Williams, M.R. Capecchi, W.R. Taylor, and K.E. Bernstein (2007). Mice with enhanced macrophage angiotensin-converting enzyme are resistant to melanoma. Am J Pathol. 170(6):2122-34.

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Last Updated: 11/2/16