Mario Capecchi is interested in the molecular genetic analysis of mammalian development, with emphasis on neurogenesis, organogenesis, patterning of the vertebral column, and limb development. He also contributes to the modeling of human disease in the mouse, from cancer to neuropsychiatric disorders.
Through a series of bold experiments begun in the 1980s, Capecchi demonstrated that he could alter any gene in a mouse cell by replacing it with a modified version. At the time, scientists were skeptical that such altered DNA could be targeted to a particular gene. But Capecchi was not to be deterred. Indeed, his studies demonstrated that it is possible to replace an intact, functional gene with a modified version that can zero in on the corresponding DNA in the chromosome.
Over the years, Capecchi has used gene targeting to systematically knock out genes in the Hox family, considered to be the master switches that control the formation of the body plan during development. Doing so produces mice with dramatic developmental defects. When Capecchi and his Utah research team completely disrupted the activity of the Hox10 and Hox11 gene families in mice, they found that both families played important roles in orchestrating the construction of the ribs, spine, and limb bones. In another experiment, Capecchi created mice without a functional Hoxb8 gene, finding that without this gene, animals groomed themselves excessively, creating bald spots and skin wounds. He suspects that defects in Hoxb8 may underlie obsessive-compulsive disorder in humans that involves excessive grooming behavior.
He and his colleagues have also developed the first accurate mouse model of alveolar rhabdomyosarcoma, an aggressive childhood muscle cancer. This new model has improved researchers\' understanding of the cause of the disease and may lead to new therapies to treat the disorder.
Nobel Prize in Physiology or Medicine 2007, with Sir Martin J. Evans and Oliver Smithies, \"for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells\"
Junior Fellow of the Society of Fellows, Harvard University, 1967-69
American Chemical Society Award in Biochemistry, 1969
Established Investigator of the American Heart Association, 1969-72
America\'s Ten Outstanding Young Men Award, 1971
National Institutes of Health Career Development Award, 1972-74
American Cancer Society Faculty Research Award, 1974-79
Taught Cold Spring Harbor Summer Course on Microinjection and DNA Transfection, 1984, 1985
Chairman of the Gordon Conference on Molecular Genetics, 1986
Distinguished Research Award, University of Utah, 1987
Chairman of Banbury Conference on Developmental Genetics, Cold Spring Harbor, 1989
Member of the National Academy of Sciences, 1991-present
Recipient of NIH MERIT grant award, 1992 to 2001
Recipient of the Fifth Annual Bristol-Myers Squibb Award for Distinguished
Achievement in Neuroscience Research, 1992
Recipient of the 1993 Gairdner Foundation International Award for Achievements in Medical Science Distinguished Professor of Human Genetics and Biology, University of Utah, 1993-present
Recipient of the 1994 General Motors Corporation\'s Alfred P. Sloan Jr. Prize for
Outstanding Basic Science Contributions to Cancer Research
Recipient of the 1996 Molecular Bioanalytics Prize, Germany- 2 -
Laureate of the 1996 Kyoto Prize in Basic Sciences
Recipient of the 1997 Franklin Medal for Advancing Our Knowledge of the Physical Sciences
Feodor Lynen Lectureship, 1998 Miami Biosymposium
Recipient of the 1998 Rosenblatt Prize for Excellence
Recipient of the 1998 Baxter Award for Distinguished Research in the Biomedical Sciences, Association of American Medical Colleges
Helen Lowe Bamberger Colby and John E. Bamberger Presidential Endowed Chair in the Health Sciences Center, University of Utah, 1999
Phi Kappa Phi National Honor Society, 1999
Lecturer in the Life Sciences for the Collège de France, 1999-2000
Recipient of the 2000 Horace Mann Distinguished Alumni Award, Antioch College
Recipient of the 2000 Premio Phoenix-Anni Verdi for Genetic Research Award, Italy
Recipient of the 33rd Jiménez-Diáz Prize for Contributions to Medical Genetics, Spain, 2001
Recipient of the 2001 Pioneers of Progress Award
Recipient of the 2001 Albert Lasker Award for Basic Medical Research
Elected to the rank of Fellow of the American Association for the Advancement of Science, 2001
Recipient of the State of Utah Governor’s Science and Technology Award, 2002
Laureate of the 2001 National Medal of Science
Recipient of NIH MERIT grant award, 2002 to 2011
Recipient of the 2002 John Scott Medal Award
Recipient of the 2002 Shaul and Meira Massry Foundation Prize
Elected to the European Academy of Sciences, 2002
Recipient of the 2003 Pezcoller Foundation-AACR International Award for Cancer Research
Recipient of the 2002/03 Wolf Prize in Medicine
Recipient of an Honorary Degree of Doctor of Medicine, University of Florence School of Medicine, Italy, 2004
Recipient of the 2005 March of Dimes Prize in Developmental Biology
2007 Jacob Heskel Gabbay Award in Biotechnology and Medicine
2007 Nobel Laureate, Physiology or Medicine with Oliver Smithies and Martin Evans
Recipient of the 2008 Distinguished Scientist Award, American Heart Association
Member of the American Academy of Arts and Sciences 2009
Wu, S., Y. Wu, M.R. Capecchi (2006). Motoneurons and oligodendrocytes are sequentially generated from neural stem cells but do not appear to share common lineage-restricted progenitors in vivo. Development 133, 581-590.
Keller, C., M. S. Hansen, C. M. Coffin and M. R. Capecchi (2004). Pax3:Fkhr interferes with embryonic Pax3 and Pax7 function: implications for alveolar rhabdomyosarcoma cell of origin. Genes Dev. 18:2608-2613.
Keller , C., B. R. Arenkiel, C. M. Coffin, N. El-Bardeesy, R. A. DePinho and M. R. Capecchi (2004). Alveolar rhabdomyosarcomas in conditional Pax3:Fkhr mice: cooperativity of Ink4a/ARF and Trp53 loss of function. Genes Dev.18:2614-2626.
Boulet AM, Moon AM, Arenkiel BR and Capecchi MR (2004) The roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth. Dev. Biol. 273, 361-372.
Arenkiel BR, Tvrdik P, Gaufo GO and Capecchi MR (2004) Hoxb1 functions in both motoneurons and tissues of the periphery to establish and maintain the proper neuronal circuitry. Genes Dev. 18, 1539-1552.
Gaufo GO, Wu S and Capecchi MR (2004) Contribution of Hox genes to the diversity of the hindbrain sensory system. Development 131, 1259-1266.
Boulet AM and Capecchi MR (2004) Multiple roles of Hoxa11 and Hoxd11 in the formation of the mammalian forelimb zeugopod. Development 131, 299-309.
Gaufo GO, Thomas KR and Capecchi MR (2003) Hox3 genes coordinate mechanisms of genetic suppression and activation in the generation of branchial and somatic motor neurons. Development 130, 5191-5201.
Vorbach C, Harrison R and Capecchi MR (2003) Xanthine oxidoreductase is central to the evolution and function of the innate immune system. Trends Immunol. 29, 512-517.
Wellik DM and Capecchi MR (2003) Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. Science 301, 363-367.
Economides KR and Capecchi MR (2003) Hoxb13 is required for normal differentiation and secretory function of the ventral prostate. Development 130, 2061-2069.
Cole J, Khokhlova N, Sutliff RL, Adams JW, Disher KM, Zhao H, Capecchi MR, Corvol P and Bernstein KE (2003) Mice lacking endothelial angiotensin-converting enzyme (ACE): normal blood pressure with elevated angiotensin II. Hypertension 41, 313-321.
Economides KD, Zeltser L and Capecchi MR (2003) Hoxb13 mutations cause overgrowth of caudal spinal cord and tail vertebrae. Dev. Biol. 256, 317-330.
Schmidt EE, Bondareva AA, Radke JR and Capecchi MR (2003) Fundamental cellular processes do not require vertebrate-specific sequences within the TATA-binding protein. J. Biol. Chem. 278, 6168-6174.
Barrow JR, Thomas KR, Boussadia-Zahui O, Moore R, Kemler R, Capecchi MR, and McMahon AP (2003) Ectodermal Wnt3/?-catenin signaling is required for the establishment and the maintenance of the apical ectodermal ridge. Genes Dev. 17, 394-409.
Vorbach C, Scriven A and Capecchi MR (2002) The housekeeping gene Xanine Oxidoreductase is necessary for milk fat droplet enveloping and secretion: gene sharing in the lactating mammary gland. Genes Dev. 16, 3223-3235.
Frank DU, Fotheringham LK, Brewer JA, Muglia LJ, Tristani-Firouzi M, Capecchi MR and Moon AM (2002) An Fgf8 mouse mutant phenocopies human 22q11 deletion syndrome. Development 129, 4591-4603.
Boulet AM and MR Capecchi (2002) Duplication of the Hoxd11gene causes alterations in the axial and appendicular skeleton of the mouse. Dev. Biol. 249, 96-107.
Hobbs NK, Bondareva AA, Barnett S, Capecchi MR and Schmidt EE (2002) Removing the vertebrate-specific TBP N-terminus disrupts placental ?2m-dependent interactions with the maternal immune system. Cell 110, 43-54.
Wellik DM, Hawkes PJ and Capecchi MR (2002) Hox11 paralogous genes are essential for metanephric kidney induction. Genes Dev. 16, 1423-1432.
Greer JM and Capecchi MR (2002) Hoxb8 is required for normal grooming behavior in the mouse. Neuron 33, 23-34.
Cole J, Quach DL, Sundaram K, Corvol P, Capecchi MR and Bernstein KE (2002) Mice lacking endothelial ACE have a normal blood pressure. Circ. Res. 90:87-92.
Capecchi MR (2001) Generating mice with targeted mutations. Nature Med. 7:1086-1090.
Capecchi MR (2001) Gene targeting: Altering the genome in mice. Ergito.
Stadler HS, Higgins KM and Capecchi MR (2001) Loss of Eph-receptor expression correlates with loss of cell adhesion and chondrogenic capacity in Hoxa13mutant limbs. Development 128, 4177-4188.
Manley NR, Barrow JR, Zhang T and Capecchi MR (2001) Hoxb2 and Hoxb4 act together to specify ventral body wall formation. Dev. Biol. 237:130-144.
Cole J, Ertoy D, Lin H, Sutliff RL, Ezan E, Guyene TT, Capecchi MR, Corvol P and Bernstein KE (2000) Mice deficient in angiotensin converting enzyme (ACE) have anemia due to a lack of angiotensin II facilitated erythropoiesis. J. Clin. Invest. 106:1391-1398.
Moon AM and Capecchi MR (2000) Fgf8 is required for outgrowth and patterning of the limbs. Nature Genet. 26: 455-459.
Gaufo GO, Flodby P and Capecchi MR (2000) Hoxb1 controls effectors of sonic hedgehog and Mash1 signaling pathways. Development 127: 5343-5354.
Schmidt EE, Taylor DS, Prigge JR, Barnett S and Capecchi MR (2000) Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids. Proc. Natl. Acad. Sci. USA 97: 13702-13707.
Moon AM, Boulet AM and Capecchi MR (2000) Normal limb development in conditional mutants of Fgf4. Development 127:989-996.
Barrow JR, Stadler HS and Capecchi MR (2000) Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse. Development 127:933-944.
Greer JM, Puetz J, Thomas KR and Capecchi MR (2000) Maintenance of functional equivalence during paralogous Hox gene evolution. Nature 403:661-665.
Capecchi MR (2000) Human germline gene therapy: How and why. In Engineering the Human Germline. (G. Stock and J. Campbell, Eds.) New York: Oxford University Press, pp. 31-42.
Rossel M and Capecchi MR (1999) Mice mutant for both Hoxa1 and Hoxb1 show extensive remodeling of the hindbrain and defects in craniofacial development. Development 126:5027-5040.
Bunting M, Bernstein KE, Greer JR, Capecchi MR and Thomas KR (1999) Targeting genes for self-excision in the germline. Genes Dev. 13:1524-1528.
Godwin AR, Stadler HS, Nakamura K and Capecchi MR. (1998) Detection of targeted GFP-Hox gene fusions during mouse embryogenesis. Proc. Natl. Acad. Sci. USA 95:13042-13047.
Godwin AR and Capecchi MR (1998) Hoxc13 mutant mice lack external hair. Genes Dev. 12:11-20.