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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. Banito A, Li X, Laporte AN, Roe JS, Sanchez-Vega F, Huang CH, Dancsok AR, Hatzi K, Chen CC, Tschaharganeh DF, Chandwani R, Tasdemir N, Jones KB, Capecchi MR, Vakoc CR, Schultz N, Ladanyi M, Nielsen TO, Lowe SW (2018). The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma. Cancer Cell 34:346-348.

  2. De, S., D. Van Deren, E. Peden, M. Hockin, A. Boulet, S. Titen and M. Capecchi (2018).  Two Distinct Ontogenies Confer Heterogeneity to Brain Microglia.  Development 145 PMID: 29973370.

  3. Banito A, Li X, Laporte AN, Roe JS, Sanchez-Vega F, Huang CH, Dancsok AR, Hatzi K, Chen CC, Tschaharganeh DF, Chandwani R, Tasdemir N, Jones KB, Capecchi MR, Vakoc CR, Schultz N, Ladanyi M, Nielsen TO, Lowe SW (2018). The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma. Cancer Cell 33:527-541 PMID: 29502955.

  4. Barrott JJ, Illum BE, Jin H, Hedberg ML, Wang Y, Grossmann A, Haldar M, Capecchi MR, Jones KB (2018). Paracrine osteoprotegerin and β-catenin stabilization support synovial sarcomagenesis in periosteal cells. J Clin Invest 128:207-218 PMID: 29202462.

  5. Langer E.M., N.D Kendsersky, C.J. Daniel, G.M. Kuziel, C. Pelz, K.M. Murphy, M.R. Capecchi and R.C. Sears (2017). ZEB1-repressed microRNAs inhibit autocrine signaling that promotes vascular mimicry of breast cancer cells. Oncogene. Oct 30. [Epub ahead of print] PMID: 29084210.

  6. Nagarajan N., B.W. Jones, P.J. West, R.E. Marc and M.R. Capecchi (2017). Corticostriatal circuit defects in Hoxb8 mutant mice. Mol Psychiatry Sep 26. [Epub ahead of print] PMID: 28948967.

  7. Barrott J.J., J.F. Zhu, K. Smith-Fry, A.M. Susko, D. Nollner, L.D. Burrell, A. Pozner, M.R. Capecchi, J.T. Yap, L.A. Cannon-Albright, X. Deng and K.B. Jones (2017). The Influential Role of BCL2 Family Members in Synovial Sarcomagenesis. Mol Cancer Res15:1733-1740 PMID: 28851813.

  8. Ruff J.S., R.B. Saffarini, L.L. Ramoz, L.C. Morrison, S. Baker, S.M. Laverty, P. Tvrdik, M.R. Capecchi and W.K. Potts (2017). Mouse fitness measures reveal incomplete functional redundancy of Hox paralogous group 1 proteins. PLoS One. 12:e0174975. eCollection 2017. PMID: 28380068.

  9. Kim G., N. Nagarajan, E. Pastuzyn, K. Jenks, M. Capecchi, J. Shepherd and R. Menon (2017). Deep-brain imaging via epi-fluorescence Computational Cannula Microscopy. Sci Rep7:44791. PMID: 28317915.

  10. Li S., H. Lan, H. Men, Y. Wu, N. Li, M.R. Capecchi, E.C. Bryda and S. Wu (2017). Derivation of Transgene-Free Rat Induced Pluripotent Stem Cells Approximating the Quality of Embryonic Stem Cells. Stem Cells Transl Med. 6:340-351. PMID: 27625042.

  11. Zhang X., X. Wei, Y. Wu, Y. Wang, C. Tan, X. Hu, N. Li, M.R. Capecchi and S. Wu (2017). Genome-wide piggyBac transposon mediated screening reveals genes related to reprogramming. Protein Cell8:134-139. PMID: 27761808.

  12. Xu C., X. Qi, X. Du, H. Zou, F. Gao, T. Feng, H. Lu, S. Li, X. An, L. Zhang, Y. Wu, Y. Liu, N. Li, M.R. Capecchi and S. Wu (2017). piggyBac mediates efficient in vivo CRISPR library screening for tumorigenesis in mice.  Proc Natl Acad Sci USA114:722-727. PMID: 28062688.

  13. Barrott J.J., L.A. Kafchinski, H. Jin, J.W. Potter, S.D. Kannan, R. Kennedy, T. Mosbruger, W.L. Wang, J.W. Tsai, D.M. Araujo, T. Liu, M.R. Capecchi, A.J. Lazar and K.B. Jones (2016). Modeling synovial sarcoma metastasis in the mouse: PI3'-lipid signaling and inflammation. J Exp Med213:2989-3005. PMID: 27956588.

  14. Wu S., M. Mariotti, D. Santesmasses, K.E. Hill, J. Baclaocos, E. Aparicio-Prat, S. Li, J. Mackrill, Y. Wu, M.T. Howard, M. Capecchi, R. Guigó, R.F. Burk and J.F. Atkins (2016). Human selenoprotein P and S variant mRNAs with different numbers of SECIS elements and inferences from mutant mice of the roles of multiple SECIS elements. Open Biol6. pii: 160241. PMID: 27881738.

  15. Lan H., S. Li, Z. Guo, H. Men, Y. Wu, N. Li, E.C. Bryda, M.R. Capecchi and S. Wu (2016). Efficient generation of selection-gene-free rat knockout models by homologous recombination in ES cells. FEBS Lett590:3416-3424. PMID: 27597178.

  16. Jones K.B., J.J. Barrott, M. Haldar, H. Jin, J.F. Zhu, M. Monument, E. Langer, R.L. Randall and M.R. Capecchi (2016).  The impact of chromosomal translocation locus and fusion oncogene coding sequence in synovial sarcomagenesis. Oncogene35:5021-32.

  17. 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.
  18. 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.
  19. Pozner, A. and Capecchi, M. (2015). ASPM regulates symmetric stem cell division by tuning Cyclin E ubiquitination. Nature Communications.6:8763.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
  26. 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.
  27. 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.
  28. 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.
  29. 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.
  30. 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.
  31. 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.
  32. 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.
  33. 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.
  34. Makki, N. and M.R. Capecchi (2012). Cardiovascular defects in a mouse model of HOXA1 syndrome. Hum. Mol. Genet.21(91):26-31.
  35. 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.
  36. 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.
  37. 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.
  38. 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.
  39. 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.
  40. Ray, R. and M.R. Capecchi (2008). An examination of the chiropteran HoxD locus from an evolutionary perspective. Evol. & Dev.10(6):657-70.
  41. 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.
  42. Capecchi, M.R. (2008). The Making of a Scientist II (Nobel Lecture). ChemBioChem9(10):1530-43.
  43. Sangiorgi, E. and M.R. Capecchi (2008). Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet. 40(7):915-20.
  44. 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.
  45. 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.
  46. 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.
  47. 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.
  48. 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.
  49. 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.
  50. 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.
  51. 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.
  52. 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.
  53. 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: 11/6/18