Nobuyo Maeda

Nobuyo Maeda
BornEarly 1950s
Sendai, Miyagi Prefecture, Japan
NationalityJapanese
EducationTohoku University
OccupationRobert H. Wagner Distinguished Professor
Years active1978-
Known forCreating the first mouse model for atherosclerosis
Medical career
InstitutionsUniversity of North Carolina at Chapel Hill
Sub-specialtiesGenetics, medical research
AwardsMethod to Extend Research in Time (MERIT) Award of the National Heart, Lung, and Blood Institute

Nobuyo N. Maeda is a Japanese geneticist and medical researcher, who works on complex human diseases including atherosclerosis, diabetes and high blood pressure, and is particularly known for creating the first mouse model for atherosclerosis. Maeda has worked in the United States since 1978; as of 2017, she is the Robert H. Wagner Distinguished Professor at the University of North Carolina at Chapel Hill.[1]

Early life and education

Maeda was born in Sendai, Miyagi Prefecture, Japan in the early 1950s, the second of three sisters. Her father was a chemical engineering professor.[2] She attended Tohoku University in Sendai, where she received a BSc in chemistry (1972) and an MSc in bio-organic chemistry (1974), followed by a PhD in the same subject in 1977; her thesis was entitled "Isolation and characterization of neurotoxins from the venoms of sea snakes, and the use of amino acid sequences in taxonomy".[3]

Career and awards

Maeda first briefly worked in the laboratory of Nobuo Tamiya at the Department of Chemistry of Tohoku University. In 1978, she left Japan for the United States, and worked for a decade at the University of Wisconsin–Madison. She held post-doctoral positions in the laboratories of Walter M. Fitch (Department of Physiological Chemistry; 1978–81) and Oliver Smithies (Laboratory of Genetics; 1981–83), and then worked in the Laboratory of Genetics as an assistant and then associate scientist.[3]

She moved to the Department of Pathology of the University of North Carolina at Chapel Hill in 1988, with her collaborator (and later husband) Smithies,[2] where she held successively positions as associate professor (1988) and professor (1996), and was appointed the Robert H. Wagner Distinguished Professor at the Department of Pathology and Laboratory Medicine in 2003.[3] She is also an adjunct professor in the Department of Nutrition (from 2000) and has directed the university's pre-doctoral training program in vascular biology since 2002.[3][4]

She was awarded the Method to Extend Research in Time (MERIT) Award of the National Heart, Lung, and Blood Institute (1998).[4]

Human apolipoprotein E

Research

Maeda's early work on sea snake venoms led to an interest in molecular evolution, which she pursued in Fitch's laboratory.[2] She published in the 1980s on molecular evolution in higher primates such as chimpanzees and humans.[5] Her work focused on the large mutational effects of recombination between members of multigene families, particularly in the human haptoglobin gene cluster.[6]

In 1987, Maeda, Smithies and coworkers used the novel technique of gene targeting – a method of replacing single mouse genes using homologous recombination developed by Smithies, Mario Capecchi and others – to correct the hypoxanthine-guanine phosphoribosyltransferase gene responsible for Lesch–Nyhan syndrome in mouse cells in vitro.[7][8] This was the second successful use of the technique to be published.[6][7] Maeda then started to apply gene targeting to elucidate the function of lipoproteins, which had been shown by Jan and Judith Rapacz to be associated with atherosclerosis in domestic pigs.[6][9] She was one of the first to apply gene-targeting methods to a complex, multifactorial disease, rather than single-gene disorders such as cystic fibrosis and Lesch–Nyhan syndrome.[10] Maeda and her coworkers found that deleting the mouse gene for apolipoprotein E (ApoE) – a component of very low-density lipoprotein – caused the animals to develop elevated blood cholesterol levels and atherosclerosis within around 6 months, on a normal diet.[6][9][11] The results were published in 1992, in a highly cited paper in Science.[12][nb 1] The ApoE knockout (apoe−/−) was the earliest mouse model of the disease, and has been widely used in atherosclerosis research.[11][14][15][nb 2]

Oliver Smithies, Maeda's husband and long-term collaborator

Maeda's group subsequently carried out other gene-targeting experiments, including replacing the mouse gene for ApoE with common variants of the human gene.[14] As of 2017, her research continues to focus on atherosclerosis, and encompasses molecular pathology as well as genetics.[1] She also researches other multifactorial diseases, including diabetes and high blood pressure.[2][4]

Personal life

Maeda was married to the British-born geneticist Oliver Smithies (1925–2017).[16]

Selected publications

  • Sunny H. Zhang; Robert L. Reddick; Jorge A. Piedrahita; Nobuyo Maeda (1992), "Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E", Science, 258 (5081): 468–71, Bibcode:1992Sci...258..468Z, doi:10.1126/science.1411543, PMID 1411543
  • Jorge A. Piedrahita; Sunny H. Zhang; John R. Hagaman; Paula M. Oliver; Nobuyo Maeda (1992), "Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells" (PDF), Proceedings of the National Academy of Sciences USA, 89 (10): 4471–75, Bibcode:1992PNAS...89.4471P, doi:10.1073/pnas.89.10.4471, PMC 49104, PMID 1584779
  • Thomas Doetschman; Ronald G. Gregg; Nobuyo Maeda; et al. (1987), "Targetted correction of a mutant HPRT gene in mouse embryonic stem cells", Nature, 330 (6148): 576–78, Bibcode:1987Natur.330..576D, doi:10.1038/330576a0, PMID 3683574, S2CID 4350881

References

Notes

  1. ^ According to Google Scholar, as of 16 January 2017, the paper had been cited 2105 times.[13]
  2. ^ A group led by Jan L. Breslow at the Rockefeller University in New York also independently created ApoE knockouts that developed atherosclerosis in 1992.[7][15]

References

  1. ^ a b DPLM Faculty Profiles — Dr. Maeda, University of North Carolina at Chapel Hill, retrieved 14 January 2017
  2. ^ a b c d Gary Moss (6 August 2013), "Separate research paths lead to a lifelong partnership", University Gazette, University of North Carolina at Chapel Hill, archived from the original on 31 August 2019, retrieved 14 January 2017
  3. ^ a b c d Curriculum Vitae of Nobuyo Maeda (PDF), University of North Carolina at Chapel Hill, retrieved 14 January 2017
  4. ^ a b c Nobuyo Maeda, PhD, University of North Carolina at Chapel Hill, retrieved 14 January 2017
  5. ^ Roger Lewin (1987), "My Close Cousin the Chimpanzee", Science, 238 (4825): 273–5, Bibcode:1987Sci...238..273L, doi:10.1126/science.3116670, JSTOR 1700679, PMID 3116670
  6. ^ a b c d Nobuyo Maeda (2011), "Development of Apolipoprotein E–Deficient Mice", Arteriosclerosis, Thrombosis, and Vascular Biology, 31 (9): 1957–62, doi:10.1161/ATVBAHA.110.220574, PMC 3286619, PMID 21849705
  7. ^ a b c The Nobel Prize in Physiology or Medicine 2007: Advanced Information, The Nobel Foundation, retrieved 16 January 2017
  8. ^ Mark Derewicz (1 January 2008), "Life at the Bench", Endeavors, retrieved 13 January 2017
  9. ^ a b Oliver Smithies; Tom Coffman (2015), "A Conversation with Oliver Smithies", Annual Review of Physiology, 77: 1–11, doi:10.1146/annurev-physiol-021014-071806, PMID 25668016, S2CID 43393155
  10. ^ John Travis (1992), "Scoring a technical knockout in mice", Science, 256 (5062): 1392–94, Bibcode:1992Sci...256.1392T, doi:10.1126/science.1351316, JSTOR 2876932, PMID 1351316
  11. ^ a b Fatemeh Ramezani Kapourchali; Gangadaran Surendiran; Li Chen; Elisabeth Uitz; Babak Bahadori; Mohammed H. Moghadasian (2014), "Animal models of atherosclerosis", World Journal of Clinical Cases, 2 (5): 126–32, doi:10.12998/wjcc.v2.i5.126, PMC 4023305, PMID 24868511
  12. ^ Sunny H. Zhang; Robert L. Reddick; Jorge A. Piedrahita; Nobuyo Maeda (1992), "Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E", Science, 258 (5081): 468–71, Bibcode:1992Sci...258..468Z, doi:10.1126/science.1411543, PMID 1411543
  13. ^ Zhang, Sunny H.; Reddick, Robert L.; Piedrahita, Jorge A.; Maeda, Nobuyo (1992), "Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E", Google Scholar, vol. 258, no. 5081, pp. 468–471, Bibcode:1992Sci...258..468Z, doi:10.1126/science.1411543, PMID 1411543, retrieved 16 January 2017
  14. ^ a b Stewart C. Whitman (2004), "A practical approach to using mice in atherosclerosis research", The Clinical Biochemist Reviews, 25 (1): 81–93, PMC 1853358, PMID 18516202
  15. ^ a b Jan L. Breslow (1996), "Mouse models of atherosclerosis", Science, 272 (5262): 685–88, Bibcode:1996Sci...272..685B, doi:10.1126/science.272.5262.685, PMID 8614828, S2CID 33508623
  16. ^ Oliver Smithies, Carolina's first Nobel laureate, passes away at 91, University of North Carolina at Chapel Hill, 11 January 2017, retrieved 13 January 2017

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