Mario Capecchi
Distinguished Professor of Human Genetics and Professor of Biology
2007 Nobel Prize Winner for Physiology or Medicine
B.S. Antioch College
Ph.D. Harvard University
Mario Capecchi's PubMed Literature Search
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 and cancer. 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. Haldar M, Hedberg M, Hockin M, Capecchi MR (2009) A CreER based random induction strategy for modeling translocation-associated sarcomas in mice. Cancer Res., In Press
2. Sangiorgi E, Capecchi MR (2009) Bmi1 lineage tracing identifies a self-renewing pancreatic acinar cell subpopulation capable of maintaining pancreatic organ homeostasis. PNAS, In Press
3. Ray R, Capecchi MR (2008) An examination of the chiropteran HoxD locus from an evolutionary perspective. Evol. & Dev. 10:6 657-670
4. Sangiorgi E, Shuhua Z, Capecchi MR (2008) In vivo evaluation of PhiC31 recombinase activity using a self-excision cassette. Nuc. Acid Res. 10.1093/nar/gkn627:1-8
5. Capecchi MR (2008) The Making of a Scientist II (Nobel Lecture). ChemBioChem. Jul 2;9(10):1530-43
6. Sangiorgi E, Capecchi MR (2008) Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet. Jul;40(7):915-20
7. Haldar M, Randall RL, Capecchi MR (2008) Synovial Sarcoma: From Genetics to Genetic-based Animal Modeling. Clin OrthopRelat Res. Sep;466(9):2156-67
8. Haldar M, Karan G, Tvrdik P, Capecchi MR (2008) Two cell lineages, Myf5-independent, participate in mouse skeletal myogenesis. Dev Cell Mar(3):14:437-445
9. Wu S, Ying G, Wu Q, Capecchi MR (2008) A protocol for constructing gene targeting vectors: generating knockout mice for the cadherin family and beyond. Nat Protocols. 3(6):1056-76
10. Vasquez SX, Hansen MS, Bahadur AN, Hockin MF, Kindlmann GL, Nevell L, Wu IQ, Grunwald DJ, Weinstein DM, Jones GM, Johnson CR, Vandeberg JL, Capecchi MR, Keller C (2008) Optimization of volumetric computed tomography for skeletal analysis of model genetic organisms. Anat Rec 291(5):475-487
11. Wu Y, Wang G, Scott SA, Capecchi MR (2008) Hoxc10 and Hoxd10 regulate mouse columnar, divisional, and motor pool identity of lumbar motoneurons. Development 135(1):171-182
12. Bondareva AA, Capecchi MR, Iverson SV, Li Y, Lopez NI, Lucas O, Merrill GF, Prigge JR, Siders AM, Wakamiya M, Wallin SL, Schmid EE (2007) Effects of thioredoxin reductase-1 deletion on embryogenesis and transcriptome. Free Radic Biol Med. Sept. 15;43(6):911-23
13. Barrow JR, Howell WD, Rule M, Hayashi S, Thomas KR, Capecchi MR, McMahon AP (2007) Wnt3 signaling in the epiblast is required for proper orientation of the anteroposterior axis. Dev. Biol. 312:312-20
14. McIntyre DC, Rakshit S, Yallowitz AR, Loken L, Jeannotte L, Capecchi MR, Wellik DM (2007) Hox patterning of the vertebrate rib cage. Development 134:2981-89
15. Wu S, Ying G, Wu Q, Capecchi MR (2007) Towards simpler and faster genome-wide mutagenesis in mice. Nat Genet. Jul;39(7):922-30
16. Shen XZ, Li P, Weiss D, Fuchs S, Xiao HD, Adams JA, Williams IR, Capecchi MR, Taylor WR, Bernstein KE (2007) Mice with enhanced macrophage angiotensin-converting enzyme are resistant to melanoma. Am J Pathol. Jun;170(6):2122-34
