David D. Moore

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David D. Moore
David D. Moore in 2017
BornAugust 21, 1952
Brookline, Massachusetts
Alma materBrown University (A.B.) University of Wisconsin–Madison (Ph.D.)
Known forDiscovery of constitutive androstane receptor, farnesoid X receptor, and small heterodimer partner
SpouseJudy Lin
Children1
AwardsEdwin B. Astwood Award, Endocrine Society (1999)

Member of the National Academy of Sciences (2019)

Transatlantic Medal, Society for Endocrinology (2021)

Adolf Windaus Prize, Falk Foundation (2022)

Fellow of the American Association for the Advancement of Science (2022)
Scientific career
FieldsMolecular biology

Endocrinology

Toxicology
InstitutionsUniversity of California, San Francisco

Massachusetts General Hospital

Harvard Medical School

Baylor College of Medicine

Korea Advanced Institute of Science and Technology

University of California, Berkeley
ThesisSequence organization of lambdoid bacteriophage origins of DNA replication (1979)
Doctoral advisorFrederick Blattner

David Dudley Moore (born August 21, 1952) is an American molecular biologist known for his work investigating nuclear hormone receptors. He is a Professor and Chair of the Department of Nutritional Sciences & Toxicology at the University of California, Berkeley. He was a founding editor for the Current Protocols series of laboratory manuals in 1987.

Moore has been a leading figure in the investigation of nuclear hormone receptors, having initially discovered and described many family members. Some of his most significant discoveries are the constitutive androstane receptor (CAR) in 1994, farnesoid X receptor (FXR) in 1995, and the small heterodimer partner (SHP) in 1996.[1][2][3][4][5]

In 2019 he was elected to the National Academy of Sciences.[1][6]

Early life and education[edit]

Moore was born in Brookline, Massachusetts in 1952, and was adopted by Clinton and Emily Moore from The Home for Little Wanderers. He was raised in Cincinnati, Ohio and graduated from Madeira High School in 1970.

After completing his undergraduate degree at Brown University in Providence, Rhode Island in 1974,[1] he received his Ph.D. in 1979 from the University of Wisconsin–Madison, studying origin of replication sequences in bacteriophage lambda under Frederick Blattner.[7]

Research career[edit]

Moore began work as a postdoctoral researcher in 1979 in the laboratory of Howard Goodman in the Department of Biochemistry and Biophysics at the University of California, San Francisco, where he studied the genetic sequence of human growth hormone and the DNA binding activity of the glucocorticoid receptor.[8][9]

Moore joined the faculty of the Department of Genetics at Harvard Medical School in 1981, and became a founding member of the Department of Molecular Biology at Massachusetts General Hospital.[1] There, Moore's research lab investigated the activity of thyroid hormone and its relation to growth hormone expression. In collaboration with P. Reed Larsen, he identified several novel thyroid hormone receptors.[10][11]

In 1987, Moore, alongside other colleagues including Frederick M Ausbel, established the laboratory manual series Current Protocols in Molecular Biology, which was acquired by Wiley in 1995 and later expanded to include additional titles.[12]

Moore published a series of studies beginning in 1994 identifying and describing the constitutive androstane receptor (CAR), a constitutively active nuclear receptor which senses and responds to endobiotic and xenobiotic substances.[3][13]

In 1996, Moore and his lab identified the small heterodimer partner (SHP), an orphan nuclear receptor without DNA-binding activity which binds other proteins to regulate their activity.[14] He found that SHP inhibits estrogen receptors as well as retinoid receptors.[4][15] He later found that SHP regulates the circadian clock in mice.[16]

In 1997, Moore was recruited to the Department of Molecular and Cellular Biology, then headed by Bert W. O'Malley, at Baylor College of Medicine in Houston, Texas. There, he identified the bile acid and xenobiotic ligands of farnesoid X-receptor, an orphan nuclear receptor he had first purified in 1995, and an upstream regulator of SHP.[5][17] He also identified androstane metabolites and xenobiotics as ligands for CAR during this time.[13][18]

The discovery of bile acid ligands for FXR led Moore and colleagues to demonstrate a strong link between nuclear hormone receptors and liver disease. He showed that disruption of CAR, FXR, and SHP leads to liver tumors,[19][20][21] hepatomegaly,[19][22] and fatty liver disease.[23][24]

Moore became professor of the Department of Nutritional Sciences & Toxicology at the University of California, Berkeley in 2020, where he became department chair in 2022.[2]

Moore's h-index is 110 and i10-index is 303, and his publications have been cited over 87,000 times as of August 2023 according to his Google Scholar page.[25]

Awards and honors[edit]

Moore has received many academic prizes for his work, including the Edwin B. Astwood Award from the Endocrine Society[26] and the Transatlantic Medal from the Society for Endocrinology.[27] Moore was elected to the National Academy of Sciences in 2019[1] and in 2022 became a fellow at the American Association for the Advancement of Science.[28]

References[edit]

  1. ^ a b c d e "David D. Moore". www.nasonline.org. Retrieved 2023-08-15.
  2. ^ a b "David Moore". Nutritional Sciences & Toxicology | University of California, Berkeley. Retrieved 2023-08-15.
  3. ^ a b Baes, M; Gulick, T; Choi, H S; Martinoli, M G; Simha, D; Moore, D D (March 1994). "A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements". Molecular and Cellular Biology. 14 (3): 1544–1552. doi:10.1128/MCB.14.3.1544. ISSN 0270-7306. PMC 358513. PMID 8114692.
  4. ^ a b Seol, W. (1998-10-01). "Inhibition of Estrogen Receptor Action by the Orphan Receptor SHP (Short Heterodimer Partner)". Molecular Endocrinology. 12 (10): 1551–1557. doi:10.1210/me.12.10.1551. ISSN 0888-8809. PMID 9773978.
  5. ^ a b Seol, W; Choi, H S; Moore, D D (January 1995). "Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors". Molecular Endocrinology. 9 (1): 72–85. doi:10.1210/mend.9.1.7760852. ISSN 0888-8809. PMID 7760852.
  6. ^ "Dr. David Moore elected into National Academy of Sciences". Baylor College of Medicine. 2019-04-30. Retrieved 2023-08-21.
  7. ^ Moore, David D.; Denniston, Katherine J.; Blattner, Frederick R. (June 1981). "Sequence organization of the origins of DNA replication in lambdoid coliphages". Gene. 14 (1–2): 91–101. doi:10.1016/0378-1119(81)90151-7. PMID 6455332.
  8. ^ Moore, D D; Marks, A R; Buckley, D I; Kapler, G; Payvar, F; Goodman, H M (February 1985). "The first intron of the human growth hormone gene contains a binding site for glucocorticoid receptor". Proceedings of the National Academy of Sciences. 82 (3): 699–702. doi:10.1073/pnas.82.3.699. ISSN 0027-8424. PMC 397113. PMID 2983311.
  9. ^ Marks, Andrew R.; Moore, David D.; Buckley, Douglas I.; Gametchu, Bahiru; Goodman, Howard M. (June 1986). "Conservation of the DNA binding domain and other properties between porcine and rat glucocorticoid receptors". Journal of Steroid Biochemistry. 24 (6): 1097–1103. doi:10.1016/0022-4731(86)90369-9. PMID 3016408.
  10. ^ Koenig, R J; Warne, R L; Brent, G A; Harney, J W; Larsen, P R; Moore, D D (July 1988). "Isolation of a cDNA clone encoding a biologically active thyroid hormone receptor". Proceedings of the National Academy of Sciences. 85 (14): 5031–5035. doi:10.1073/pnas.85.14.5031. ISSN 0027-8424. PMC 281681. PMID 2899322.
  11. ^ Prost, E.; Koenig, R. J.; Moore, D. D.; Larsen, P. R.; Whalen, R. G. (1988-07-11). "Multiple sequences encoding potential thyroid hormone receptors isolated from mouse skeletal muscle cDNA libraries". Nucleic Acids Research. 16 (13): 6248. doi:10.1093/nar/16.13.6248. ISSN 0305-1048. PMC 336883. PMID 3399404.
  12. ^ Current Protocols in Molecular Biology. Wiley. doi:10.1002/(issn)1934-3647.
  13. ^ a b Honkakoski, Paavo; Moore, Rick; Washburn, Kimberly A.; Negishi, Masahiko (1998-04-01). "Activation by Diverse Xenochemicals of the 51-Base Pair Phenobarbital-Responsive Enhancer Module in the CYP2B10 Gene". Molecular Pharmacology. 53 (4): 597–601. doi:10.1124/mol.53.4.597. ISSN 0026-895X. PMID 9547348. S2CID 38390000.
  14. ^ Seol, Wongi; Choi, Hueng-Sik; Moore, David D. (1996-05-31). "An Orphan Nuclear Hormone Receptor That Lacks a DNA Binding Domain and Heterodimerizes with Other Receptors". Science. 272 (5266): 1336–1339. doi:10.1126/science.272.5266.1336. ISSN 0036-8075. PMID 8650544. S2CID 32853062.
  15. ^ Lee, Yoon-Kwang; Dell, Helen; Dowhan, Dennis H.; Hadzopoulou-Cladaras, Margarita; Moore, David D. (2000-01-01). "The Orphan Nuclear Receptor SHP Inhibits Hepatocyte Nuclear Factor 4 and Retinoid X Receptor Transactivation: Two Mechanisms for Repression". Molecular and Cellular Biology. 20 (1): 187–195. doi:10.1128/MCB.20.1.187-195.2000. ISSN 1098-5549. PMC 85074. PMID 10594021.
  16. ^ Wu, Nan; Kim, Kang Ho; Zhou, Ying; Lee, Jae Man; Kettner, Nicole M.; Mamrosh, Jennifer L.; Choi, Sungwoo; Fu, Loning; Moore, David D. (2016-09-01). "Small Heterodimer Partner (NR0B2) Coordinates Nutrient Signaling and the Circadian Clock in Mice". Molecular Endocrinology. 30 (9): 988–995. doi:10.1210/me.2015-1295. ISSN 0888-8809. PMC 5004116. PMID 27427832.
  17. ^ Parks, Derek J.; Blanchard, Steven G.; Bledsoe, Randy K.; Chandra, Gyan; Consler, Thomas G.; Kliewer, Steven A.; Stimmel, Julie B.; Willson, Timothy M.; Zavacki, Ann Marie; Moore, David D.; Lehmann, Jürgen M. (1999-05-21). "Bile Acids: Natural Ligands for an Orphan Nuclear Receptor". Science. 284 (5418): 1365–1368. doi:10.1126/science.284.5418.1365. ISSN 0036-8075. PMID 10334993.
  18. ^ Forman, Barry M.; Tzameli, Iphigenia; Choi, Hueng-Sik; Chen, Jasmine; Simha, Devendranath; Seol, Wongi; Evans, Ronald M.; Moore, David D. (October 1998). "Androstane metabolites bind to and deactivate the nuclear receptor CAR-β". Nature. 395 (6702): 612–615. doi:10.1038/26996. ISSN 0028-0836. PMID 9783588. S2CID 4387623.
  19. ^ a b Huang, Wendong; Zhang, Jun; Washington, Michele; Liu, Jun; Parant, John M.; Lozano, Guillermina; Moore, David D. (2005-06-01). "Xenobiotic Stress Induces Hepatomegaly and Liver Tumors via the Nuclear Receptor Constitutive Androstane Receptor". Molecular Endocrinology. 19 (6): 1646–1653. doi:10.1210/me.2004-0520. ISSN 0888-8809. PMID 15831521.
  20. ^ Yang, Fan; Huang, Xiongfei; Yi, Tangsheng; Yen, Yun; Moore, David D.; Huang, Wendong (2007-02-01). "Spontaneous Development of Liver Tumors in the Absence of the Bile Acid Receptor Farnesoid X Receptor". Cancer Research. 67 (3): 863–867. doi:10.1158/0008-5472.CAN-06-1078. ISSN 0008-5472. PMID 17283114.
  21. ^ Zhang, Yuxia; Xu, Ping; Park, Kyungtae; Choi, Yunhee; Moore, David D.; Wang, Li (July 2008). "Orphan receptor small heterodimer partner suppresses tumorigenesis by modulating cyclin D1 expression and cellular proliferation". Hepatology. 48 (1): 289–298. doi:10.1002/hep.22342. PMC 3800167. PMID 18537191.
  22. ^ Dong, Bingning; Lee, Ju-Seog; Park, Yun-Yong; Yang, Feng; Xu, Ganyu; Huang, Wendong; Finegold, Milton J.; Moore, David D. (2015-02-09). "Activating CAR and β-catenin induces uncontrolled liver growth and tumorigenesis". Nature Communications. 6 (1): 5944. doi:10.1038/ncomms6944. ISSN 2041-1723. PMC 4324535. PMID 25661872.
  23. ^ Huang, Jiansheng; Iqbal, Jahangir; Saha, Pradip K.; Liu, Jun; Chan, Lawrence; Hussain, M. Mahmood; Moore, David D.; Wang, Li (July 2007). "Molecular characterization of the role of orphan receptor small heterodimer partner in development of fatty liver". Hepatology. 46 (1): 147–157. doi:10.1002/hep.21632. PMID 17526026. S2CID 3964219.
  24. ^ Dong, Bingning; Saha, Pradip K.; Huang, Wendong; Chen, Wenling; Abu-Elheiga, Lutfi A.; Wakil, Salih J.; Stevens, Robert D.; Ilkayeva, Olga; Newgard, Christopher B.; Chan, Lawrence; Moore, David D. (2009-11-03). "Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease". Proceedings of the National Academy of Sciences. 106 (44): 18831–18836. doi:10.1073/pnas.0909731106. ISSN 0027-8424. PMC 2773998. PMID 19850873.
  25. ^ "David D. Moore". scholar.google.com. Retrieved 2023-08-21.
  26. ^ "Past Laureate Award Recipients". www.endocrine.org. 2022-09-28. Retrieved 2023-08-21.
  27. ^ Endocrinology, Society for (2021-10-18). "Meet David Moore the Society's 2021 Transatlantic Medal Lecturer". The Endocrine Post. Retrieved 2023-08-21.
  28. ^ "New fellows of the American Association for the Advancement of Science". Berkeley. 2022. Retrieved 2023-08-21.
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