David Moore (biologist)

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David Moore
David Moore in Office in 2022.png
David Moore in 2017
BornDavid Dudley Moore
(1952-08-21) August 21, 1952 (age 71)
Brookline, Massachusetts
Alma mater Brown 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
Awards Edwin B. Astwood Award, Endocrine Society (1999)

Member of the National Academy of Sciences (2019)

Transatlantic Medal, Society for Endocrinology (2021)

Contents

Adolf Windaus Prize, Falk Foundation (2022)

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

Endocrinology

Toxicology
Institutions University 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
Thesis Sequence organization of lambdoid bacteriophage origins of DNA replication  (1979)
Doctoral advisor Frederick 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

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

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

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]

Related Research Articles

<span class="mw-page-title-main">Estrogen receptor</span> Proteins activated by the hormone estrogen

Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors, which are members of the nuclear receptor family of intracellular receptors, and membrane estrogen receptors (mERs), which are mostly G protein-coupled receptors. This article refers to the former (ER).

<span class="mw-page-title-main">Estrogen receptor alpha</span> Protein-coding gene in the species Homo sapiens

Estrogen receptor alpha (ERα), also known as NR3A1, is one of two main types of estrogen receptor, a nuclear receptor that is activated by the sex hormone estrogen. In humans, ERα is encoded by the gene ESR1.

<span class="mw-page-title-main">Farnesoid X receptor</span> Protein-coding gene in the species Homo sapiens

The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4, is a nuclear receptor that is encoded by the NR1H4 gene in humans.

<span class="mw-page-title-main">Liver X receptor</span> Nuclear receptor

The liver X receptor (LXR) is a member of the nuclear receptor family of transcription factors and is closely related to nuclear receptors such as the PPARs, FXR and RXR. Liver X receptors (LXRs) are important regulators of cholesterol, fatty acid, and glucose homeostasis. LXRs were earlier classified as orphan nuclear receptors, however, upon discovery of endogenous oxysterols as ligands they were subsequently deorphanized.

<span class="mw-page-title-main">Pregnane X receptor</span> Mammalian protein found in Homo sapiens

In the field of molecular biology, the pregnane X receptor (PXR), also known as the steroid and xenobiotic sensing nuclear receptor (SXR) or nuclear receptor subfamily 1, group I, member 2 (NR1I2) is a protein that in humans is encoded by the NR1I2 gene.

<span class="mw-page-title-main">Constitutive androstane receptor</span> Protein-coding gene in humans

The constitutive androstane receptor (CAR) also known as nuclear receptor subfamily 1, group I, member 3 is a protein that in humans is encoded by the NR1I3 gene. CAR is a member of the nuclear receptor superfamily and along with pregnane X receptor (PXR) functions as a sensor of endobiotic and xenobiotic substances. In response, expression of proteins responsible for the metabolism and excretion of these substances is upregulated. Hence, CAR and PXR play a major role in the detoxification of foreign substances such as drugs.

<span class="mw-page-title-main">Nuclear receptor</span> Protein

In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These intracellular receptors work with other proteins to regulate the expression of specific genes, thereby controlling the development, homeostasis, and metabolism of the organism.

<span class="mw-page-title-main">Cholesterol 7 alpha-hydroxylase</span> Protein-coding gene in the species Homo sapiens

Cholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the CYP7A1 gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enzyme, which belongs to the oxidoreductase class, and converts cholesterol to 7-alpha-hydroxycholesterol, the first and rate limiting step in bile acid synthesis.

<span class="mw-page-title-main">Rev-Erb</span> Type of protein

The Rev-Erb proteins are members of the nuclear receptor (NR) superfamily of intracellular transcription factors and key regulatory components of the circadian clock. There are two forms of the receptor, Rev-Erb alpha and Rev-Erb beta, which are each encoded by a separate gene . 

<span class="mw-page-title-main">Liver receptor homolog-1</span> Protein-coding gene in the species Homo sapiens

The liver receptor homolog-1 (LRH-1) also known as totipotency pioneer factor NR5A2 is a protein that in humans is encoded by the NR5A2 gene. LRH-1 is a member of the nuclear receptor family of intracellular transcription factors.

<span class="mw-page-title-main">Small heterodimer partner</span> Protein found in humans

The small heterodimer partner (SHP) also known as NR0B2 is a protein that in humans is encoded by the NR0B2 gene. SHP is a member of the nuclear receptor family of intracellular transcription factors. SHP is unusual for a nuclear receptor in that it lacks a DNA binding domain. Therefore, it is technically neither a transcription factor nor nuclear receptor but nevertheless it is still classified as such due to relatively high sequence homology with other nuclear receptor family members.

<span class="mw-page-title-main">Rev-ErbA alpha</span> Protein-coding gene in the species Homo sapiens

Rev-Erb alpha (Rev-Erbɑ), also known as nuclear receptor subfamily 1 group D member 1 (NR1D1), is one of two Rev-Erb proteins in the nuclear receptor (NR) family of intracellular transcription factors. In humans, REV-ERBɑ is encoded by the NR1D1 gene, which is highly conserved across animal species.

<span class="mw-page-title-main">Rev-ErbA beta</span> Protein-coding gene in the species Homo sapiens

Rev-Erb beta (Rev-Erbβ), also known as nuclear receptor subfamily 1 group D member 2 (NR1D2), is a member of the Rev-Erb protein family. Rev-Erbβ, like Rev-Erbα, belongs to the nuclear receptor superfamily of transcription factors and can modulate gene expression through binding to gene promoters. Together with Rev-Erbα, Rev-Erbβ functions as a major regulator of the circadian clock. These two proteins are partially redundant. Current research suggests that Rev-Erbβ is less important in maintaining the circadian clock than Rev-Erbα; knock-out studies of Rev-Erbα result in significant circadian disruption but the same has not been found with Rev-Erbβ. Rev-Erbβ compensation for Rev-Erbα varies across tissues, and further research is needed to elucidate the separate role of Rev-Erbβ.

<span class="mw-page-title-main">Bert W. O'Malley</span> American endocrinologist

Bert W. O'Malley is an endocrinologist from the United States. He was born in 1936 in the Garfield section of Pittsburgh, Pennsylvania. He received his early education at Catholic primary schools and Central Catholic High School, before pursuing higher education at the University of Pittsburgh, where he completed both his undergraduate and medical studies, graduating first in his class. It was here that he met Sally, who would become his wife and lifelong partner. The couple went on to have four children.

<span class="mw-page-title-main">Retinoid X receptor alpha</span> Protein-coding gene in the species Homo sapiens

Retinoid X receptor alpha (RXR-alpha), also known as NR2B1 is a nuclear receptor that in humans is encoded by the RXRA gene.

<span class="mw-page-title-main">Hepatocyte nuclear factor 4 alpha</span> Protein-coding gene in the species Homo sapiens

Hepatocyte nuclear factor 4 alpha (HNF4A) also known as NR2A1 is a nuclear receptor that in humans is encoded by the HNF4A gene.

<span class="mw-page-title-main">Retinoic acid receptor alpha</span> Protein found in humans

Retinoic acid receptor alpha (RAR-α), also known as NR1B1, is a nuclear receptor that in humans is encoded by the RARA gene.

<span class="mw-page-title-main">Liver X receptor alpha</span> Nuclear receptor protein found in humans

Liver X receptor alpha (LXR-alpha) is a nuclear receptor protein that in humans is encoded by the NR1H3 gene.

<span class="mw-page-title-main">Thyroid hormone receptor alpha</span> Protein-coding gene in the species Homo sapiens

Thyroid hormone receptor alpha (TR-alpha) also known as nuclear receptor subfamily 1, group A, member 1 (NR1A1), is a nuclear receptor protein that in humans is encoded by the THRA gene.

<span class="mw-page-title-main">Liver X receptor beta</span> Protein-coding gene in the species Homo sapiens

Liver X receptor beta (LXR-β) is a member of the nuclear receptor family of transcription factors. LXR-β is encoded by the NR1H2 gene.

References

  1. 1 2 3 4 5 "David D. Moore". www.nasonline.org. Retrieved 2023-08-15.
  2. 1 2 "David Moore". Nutritional Sciences & Toxicology | University of California, Berkeley. Retrieved 2023-08-15.
  3. 1 2 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. 1 2 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. 1 2 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. 1 2 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. 1 2 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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