Bert W. O'Malley

Bert W. O’Malley, M.D. (from an award citation)

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Dr. Bert O’Malley is currently the Tom Thompson Distinguished Service Professor of Molecular and Cellular Biology at Baylor College of Medicine (BCM). He was born in Pittsburgh and graduated from the University of Pittsburgh and the University of Pittsburgh School of Medicine and did his clinical residency at Duke University Medical Center. He is married to Sally A. O’Malley and they have four children, Sally Jr, Bert Jr, Becky, and Erin. For his training in research, he spent four years at the NIH where by the time he left, he was a Molecular Biology Section Head at NICHD. From Vanderbilt University, as the Birch Professor and Director of the Reproductive Biology Center, he moved to Baylor College of Medicine as Professor and Chairman of Molecular and Cellular Biology where he built one of the finest basic science departments in the country over the next 30+ years. This department was one of the first of a new generation of departments which combined the merging disciplines of cell structure, cell signaling, molecular biology, and developmental biology into a unified Department of Molecular and Cellular Biology. He spearheaded it to the number one ranking department of its type in the country (in NIH awards).

Dr. O’Malley’s laboratory has been a leader in uncovering the mode of action of the female sex steroids (progesterone and estrogen). By virtue of O’Malley’s pioneering work, we now understand that the primary actions of steroid hormones and nuclear receptors occur at the level of gene transcription to regulate synthesis of messenger RNAs^(1,2). After proving the pathway of action from hormone to gene to protein⁽³⁾, he then went on to discover the ‘missing link regulators’ (coactivators/corepressors) in hormone action, molecules that decipher the transcriptional instructions inherent in the receptors to activate or repress genes^(4-9). The nuclear receptor coactivators are ‘master genes’ that have immense regulatory influences on tissue development and physiology because they activate subfamilies of genes in a manner designed to coordinately regulate growth and metabolism^{(13,14,17,19)}. After discovering them, he elucidated their mode of action, their regulation, and their degradation pathways(^11,12,15,16). Of course, dysfunction in the coactivators (or corepressors) leads to serious consequences where such inherited dysfunction has been demonstrated to be causal in diverse instances of reproductive tissue differentiation, embryonic lethality and defective growth, mental retardation, metabolic regulation and numerous cancers^(7,9,10,19). O’Malley described the immense applications of coactivators to genesis and prevention of pathologies, especially those of breast cancer, inflammation, and metabolism. His work led to our molecular understanding of how hormonal antagonist drugs (e.g., Tamoxifen and RU486) work and has had a major impact on the fields of endocrinology, reproduction, genetic disease, and endocrine cancers of the breast and prostate⁽⁸⁾.

Dr. O’Malley is considered as a founding father of the field of Molecular Endocrinology and has trained numerous current leaders in this and related fields⁽²⁰⁾. He served as President of the Endocrine Society in 1985. Dr. O’Malley is a member of the National Academy of Sciences and the Institute of Medicine, and he is a Fellow of the American Academy of Arts and Sciences and the American Academy of Microbiology, and he is a Fellow of the AAAS. His participation as Chairs of the ACS, NIH Endocrine Study Section and NAS Section 42 and as President of the Endocrine Society reflect only a few of his numerous commitments to ‘national science’. Dr. O’Malley has received honorary doctorate degrees from the Karolinska Institute, New York University, the National University of Ireland, and The University of Maryland. Among many awards and honors, he has received the Ernst Oppenheimer Award, the Gregory Pincus Medal, the Lila Gruber Award, the Borden Award, the Dickson Prize, the Axel Munthe Award, the Bicentennial Medallion of Distinction (University of Pittsburgh), the Kodak Award, the Doisy Lecture Award, the D.R. Edwards Medal, the Fred Conrad Koch Medal, the E.E.S. Transatlantic Medal, the Rodbell Award (NIEHS), the Feltrinelli International Prize in Biology, the Brinker International Award in Breast Cancer, Induction into the Royal Academy of Medicine (IRE), George W. Beadle Award, Solomon Berson L. Ad. (Amer. Phy. Soc.), Pioneer Award, Woods Hole, Biolink Scientist of the Year Award, Vanderbilt Distinguished Medical Award (Alumni Assoc.), the Bowman Distinguished Geneticist Award, the Pasarow Award in Cancer Research, the Pink Ribbon Hero Award for Breast Cancer, Legacy Laureate Award (UPMC), and the Carl G. Hartman Award (SSR). He has published over 600 papers and holds 20 patents in the fields of Gene Regulation, Molecular Endocrinology and Steroid Receptor Action.

The O’Malley laboratory contributed much to the concept of ‘team science’ ⁽²⁰⁾. He has graduated over 250 trainees (students/postdoctoral fellows), who populate the world as Professors, CEOs, or Deans. He initiated the NICHD Reproductive Centers’ Program as the first PI of such a Center at Vanderbilt in the mid-sixties; he also heads one of the oldest running NIH Reproductive Training Grants and Programs in the US. He also administers (with Ron Evans, Salk) the national program in Nuclear Receptors and Transcriptional Coregulator Proteins, termed NURSA, a program funded by NIDDK as the lead NIH institute. He is a Distinguished Professor and scholar at BCM and is valued for his administrative skills and for his continued participation as an award-winning teacher in multiple yearly courses.

References for Research Discoveries

1. Means, A.R., J.P. Comstock, G.C. Rosenfeld and B.W. O’Malley. Ovalbumin mRNA of chick oviduct: partial characterization, estrogen dependence and translation in vitro. Proc. Natl. Acad. Sci. 69:1146-50, 1972.

2. Chan, L., Means, A.R., and B.W. O’Malley. Rates of Induction of specific translatable messenger RNAs for ovalbumin and avidin by steroid hormones. Proc. Natl. Acad. Sci. 70: 1870-1874, 1973.

3. Allan, G.F., X. Leng, S.Y. Tsai, N.L. Weigel, D.P. Edwards, M.-J. Tsai and B.W. O’Malley. Hormone and antihormone induce distinct conformational changes which are central to steroid receptor activation. J. Biol. Chem. 267:19513-19520, 1992.

4. McDonnell D.P. Vegeto E., and B.W. O’Malley. Identification of a negative regulatory function for steroid receptors. Proc Natl Acad Sci. 89: 10563-67,1992.

5. Baniahmad A, Leng X, Burris TP, Tsai SY, Tsai MJ, and B. W. O'Malley. The tau 4 activation domain of the thyroid hormone receptor is required for release of a putative corepressor(s) necessary for transcriptional silencing. Mol Cell Biol. Jan; 15(1):76-86, 1995.

6. Oñate, S.A., S.Y. Tsai, M.-J. Tsai and B.W. O’Malley. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science 270:1354-1357, 1995.

7. Xu, J., Qui, Y., F.J. DeMayo, S.Y. Tsai, M.-J. Tsai, and B.W. O’Malley. Disruption of the Steroid Receptor Coactivator 1 (SRC-1) Gene in Mice Results in A Syndrome of Partial Hormone Resistance. Science 279:1922-1925, 1998.

8. Smith CL, Nawaz Z, O'Malley BW. Coactivator and corepressor regulation of the agonist/antagonist activity of the mixed antiestrogen, 4-hydroxytamoxifen. Mol Endocrinol. 1997 (6):657-66.

9. Xu, J., L. Liao, G. Ning, H. Yoshida-Komiya, C. Deng and B.W. O’Malley. The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIB1/ACTR/TRAM-1) is required for normal growth, puberty, reproductive function and mammary gland development. Proc. Natl. Acad. Sci. 97:6379-6384, 2000.

10. Kuang, S.-Q., L. Liao, H. Zhang, A.V. Lee, B.W. O’Malley and J. Xu. AIB1/SRC-3 deficiency affects insulin-like growth factor I signaling pathway and suppresses v-Ha-ras-induced breast cancer initiation and progression in mice. Cancer Research 64:1875-1885, 2004.

11. Wu, R.-C., J. Qin., Y. Ping, J. Wong, S.Y. Tsai, M.-J. Tsai and B.W. O’Malley. Selective phosphorylation of SRC-3/AIB1 coactivator integrates genomic responses to multiple cellular signaling. Molec. Cell 15: 1-20, 2004.

12. Li X, Lonard DM, Jung SY, Malovannaya A, Feng O, Qin J, Tsai SY, Tsai MJ, B.W. O’Malley. The SRC-3/AIB1 coactivator is degraded in a unbiquitin- and ATP- independent manner by the REGgamma proteasome. Cell 124:3891-92, 2006.

13. O’Malley BW. Evolution of the Coregulator Master Genes: Genes that code for ‘little molecules with big goals. Science 313:1749-50, 2006.

14. Yu C, York B. Wang S, Feng Q, Xu J, O’Malley BW. An essential function of the SRC-3 coactivator in suppression of cytokine mRNA translation and inflammatory response. Molec. Cell. 25:765-78, 2007.

15. Li X., L. Amazit, W.Long, D. M.Lonard, J. J. Monaco and B. W. O’Malley. Ubiquitin- and ATP-independent Proteolytic turnover of p21 by the REGγ-proteasome pathway Molecular Cell, 26(6)831-842, 2007.

16. Wu, R.-C., Q. Feng, D.M. Lonard and B.W. O’Malley. SRC-3 Coactivator Functional Lifetime Is Regulated by a Phospho-Dependent Ubiquitin Time Clock. Cell, 6:1125-40, 2007.

17. Lonard, D. and B.W. O’Malley. The expanding cosmos of nuclear receptor coactivators. Cell. 125:411-414, 2006.

18. Lonard, D.M. and B.W. O’Malley. Nuclear receptor coregulators: Judges, juries and executioners of transcriptional regulation. Molecular Cell 27:691-700, 2007.

19. D.M. Lonard, R.B. Lanz and B.W. O’Malley. Nuclear Receptor Coregulators and Human Disease. Endocrine Revs, 28 (5): 575. (2007)

20. O’Malley, B.W. Perspective: A life-long search for the molecular pathways of steroid hormone action. Mol. Endo. 19: 1402 – 1411, 2005