David Lonard, Ph.D.
Picture
David Lonard, Ph.D.
Professor
Positions
- Professor
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Mol & Cell Biology-Mol.Regulation
Baylor College of Medicine
Houston, TX US
- Member
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Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States
Addresses
- BCM-Michael DeBakey Center (Office)
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Room: BCMM-M809
Houston, TX 77030
United States
- BCM-Michael DeBakey Center (Lab)
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Room: BCMM-M809
Houston, TX 77030
United States
Education
- Advanced Training from Baylor College Of Medicine
- 01/2002 - Houston, TX United States
- Ph.D. from Texas A&M University
- 01/1996 - College Station, TX United States
- B.S. from Texas A&M University
- 01/1992 - College Station, TX United States
Certifications
- Associate Professor
- Baylor College of Medicine
Professional Interests
- Research interests
Professional Statement
My laboratory is interested in delineating the molecular mechanisms that link proteasome-mediated protein degradation to nuclear receptor mediated gene expression and coactivator function. As a postdoctoral fellow in Dr. Bert O’Malley’s group, I was able to establish that the ubiquitin-proteasome pathway is required for efficient transcription mediated through the estrogen receptor and other nuclear receptors. These studies established that the proteasome has complex and dynamic effects on the function of steroid receptor coactivator (SRC) family members. My current interests are focused on taking advantage of these basic findings to design high throughput small molecule inhibitors (SMIs) to target these coactivators. Given the pleiotropic roles of SRC family coactivators in cancer, energy metabolism and reproduction, we plan to develop novel coactivator-targeting compounds as therapeutic agents to treat or control these broad pathological and physiological states. Through high throughput screening of small molecule compound libraries, we have identified agents that are able to inhibit SRC function.Websites
Selected Publications
- Li X, Lonard DM, O'Malley BW "A contemporary understanding of progesterone receptor function.." Mech. Ageing Dev..;125(41558):669-78. Pubmed PMID: 15541762
- He B, Feng Q, Mukherjee A, Lonard DM, DeMayo FJ, Katzenellenbogen BS, Lydon JP, O'Malley BW "A repressive role for prohibitin in estrogen signaling.." Mol. Endocrinol.. 2008 Feb;22(2):344-60. Pubmed PMID: 17932104
- Yi P, Feng Q, Amazit L, Lonard DM, Tsai SY, Tsai MJ, O'Malley BW "Atypical protein kinase C regulates dual pathways for degradation of the oncogenic coactivator SRC-3/AIB1.." Mol. Cell. 2008 Feb 29;29(4):465-76. Pubmed PMID: 18313384
- Lonard DM, O'Malley BW "Chapter 4 emerging roles of the ubiquitin proteasome system in nuclear hormone receptor signaling.." Prog Mol Biol Transl Sci. 2009;87:117-35. Pubmed PMID: 20374703
- Yu G, Zhao Y, He J, Lonard DM, Mao CA, Wang G, Li M, Li X "Comparative analysis of REG{gamma} expression in mouse and human tissues.." J Mol Cell Biol. 2010 Aug;2(4):192-8. Pubmed PMID: 20494959
- Long W, Foulds CE, Qin J, Liu J, Ding C, Lonard DM, Solis LM, Wistuba II, Qin J, Tsai SY, Tsai MJ, O'Malley BW "ERK3 signals through SRC-3 coactivator to promote human lung cancer cell invasion.." J. Clin. Invest.. 2012 May 1;122(5):1869-80. Pubmed PMID: 22505454
- Lonard DM, O'Malley BW "Expanding functional diversity of the coactivators.." Trends Biochem. Sci.. 2005 Mar;30(3):126-32. Pubmed PMID: 15752984
- Lonard DM, O'Malley BW "Gene transcription: two worlds merged.." Nature. 2008 Apr 24;452(7190):946-7. Pubmed PMID: 18432236
- Dennis AP, Lonard DM, Nawaz Z, O'Malley BW "Inhibition of the 26S proteasome blocks progesterone receptor-dependent transcription through failed recruitment of RNA polymerase II.." J. Steroid Biochem. Mol. Biol.. 2005 Mar;94(4):337-46. Pubmed PMID: 15857753
- Lonard DM, Kumar R, O'Malley BW "Minireview: the SRC family of coactivators: an entree to understanding a subset of polygenic diseases?." Mol. Endocrinol.. 2010 Feb;24(2):279-85. Pubmed PMID: 19846539
- Luo Z, Xu X, Gu P, Lonard D, Gunaratne PH, Cooney AJ, Azencott R "miRNA regulatory circuits in ES cells differentiation: a chemical kinetics modeling approach.." PLoS ONE. 2011;6(10):e23263. Pubmed PMID: 22039400
- Stanisic V, Lonard DM, O'Malley BW "Modulation of steroid hormone receptor activity.." Prog. Brain Res.. 2010;181:153-76. Pubmed PMID: 20478437
- Lonard DM, Smith CL "Molecular perspectives on selective estrogen receptor modulators (SERMs): progress in understanding their tissue-specific agonist and antagonist actions.." Steroids. 2002 Jan;67(1):15-24. Pubmed PMID: 11728517
- Han SJ, Lonard DM, O'Malley BW "Multi-modulation of nuclear receptor coactivators through posttranslational modifications.." Trends Endocrinol. Metab.. 2009 Jan;20(1):41501. Pubmed PMID: 19019695
- Lonard DM, Lanz RB, O'Malley BW "Nuclear receptor coregulators and human disease.." Endocr. Rev.. 2007 Aug;28(5):575-87. Pubmed PMID: 17609497
- Lonard DM, O'malley BW "Nuclear receptor coregulators: judges, juries, and executioners of cellular regulation.." Mol. Cell. 2007 Sep 7;27(5):691-700. Pubmed PMID: 17803935
- Lonard DM, O'Malley BW "Nuclear receptor coregulators: modulators of pathology and therapeutic targets.." Nat Rev Endocrinol. 2012 Oct;8(10):598-604. Pubmed PMID: 22733267
- Stanisic V, Malovannaya A, Qin J, Lonard DM, O'Malley BW "OTU Domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) deubiquitinates estrogen receptor (ER) alpha and affects ERalpha transcriptional activity.." J. Biol. Chem.. 2009 Jun 12;284(24):16135-45. Pubmed PMID: 19383985
- Geng C, He B, Xu L, Barbieri CE, Eedunuri VK, Chew SA, Zimmermann M, Bond R, Shou J, Li C, Blattner M, Lonard DM, Demichelis F, Coarfa C, Rubin MA, Zhou P, O'Malley BW, Mitsiades N "Prostate cancer-associated mutations in speckle-type POZ protein (SPOP) regulate steroid receptor coactivator 3 protein turnover.." Proc. Natl. Acad. Sci. U.S.A.. 2013 Apr 23;110(17):6997-7002. Pubmed PMID: 23559371
- Nawaz Z, Lonard DM, Dennis AP, Smith CL, O'Malley BW "Proteasome-dependent degradation of the human estrogen receptor.." Proc. Natl. Acad. Sci. U.S.A.. 1999 Mar 2;96(5):1858-62. Pubmed PMID: 10051559
- Cavarretta IT, Mukopadhyay R, Lonard DM, Cowsert LM, Bennett CF, O'Malley BW, Smith CL "Reduction of coactivator expression by antisense oligodeoxynucleotides inhibits ERalpha transcriptional activity and MCF-7 proliferation.." Mol. Endocrinol.. 2002 Feb;16(2):253-70. Pubmed PMID: 11818499
- Liu J, Yu G, Zhao Y, Zhao D, Wang Y, Wang L, Liu J, Li L, Zeng Y, Dang Y, Wang C, Gao G, Long W, Lonard DM, Qiao S, Tsai MJ, Zhang B, Luo H, Li X "REGgamma modulates p53 activity by regulating its cellular localization.." J. Cell. Sci.. 2010 Dec 1;123:4076-84. Pubmed PMID: 21084564
- Lonard DM, Tsai SY, O'Malley BW "Selective estrogen receptor modulators 4-hydroxytamoxifen and raloxifene impact the stability and function of SRC-1 and SRC-3 coactivator proteins.." Mol. Cell. Biol.. 2004 Jan;24(1):14-24. Pubmed PMID: 14673139
- Wang Y, Lonard DM, Yu Y, Chow DC, Palzkill TG, O'Malley BW "Small Molecule Inhibition of the Steroid Receptor Coactivators, SRC-3 and SRC-1.." Mol. Endocrinol.. 2011 Dec;25(12):2041-53. Pubmed PMID: 22053001
- Yan F, Gao X, Lonard DM, Nawaz Z "Specific ubiquitin-conjugating enzymes promote degradation of specific nuclear receptor coactivators.." Mol. Endocrinol.. 2003 Jul;17(7):1315-31. Pubmed PMID: 12663742
- Wu RC, Feng Q, Lonard DM, O'Malley BW "SRC-3 coactivator functional lifetime is regulated by a phospho-dependent ubiquitin time clock.." Cell. 2007 Jun 15;129(6):1125-40. Pubmed PMID: 17574025
- Yi P, Xia W, Wu RC, Lonard DM, Hung MC, O'Malley BW "SRC-3 coactivator regulates cell resistance to cytotoxic stress via TRAF4-mediated p53 destabilization.." Genes Dev.. 2013 Feb 1;27(3):274-87. Pubmed PMID: 23388826
- Lonard DM, O'Malley BW "SRC-3 transcription-coupled activation, degradation, and the ubiquitin clock: is there enough coactivator to go around in cells?." 2008;1(13):pe16. Pubmed PMID: 18385039
- Lonard DM, Nawaz Z, Smith CL, O'Malley BW "The 26S proteasome is required for estrogen receptor-alpha and coactivator turnover and for efficient estrogen receptor-alpha transactivation.." Mol. Cell. 2000 Jun;5(6):939-48. Pubmed PMID: 10911988
- Nawaz Z, Lonard DM, Smith CL, Lev-Lehman E, Tsai SY, Tsai MJ, O'Malley BW "The Angelman syndrome-associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily.." Mol. Cell. Biol.. 1999 Feb;19(2):1182-9. Pubmed PMID: 9891052
- Lonard DM, O'Malley BW "The expanding cosmos of nuclear receptor coactivators.." Cell. 2006 May 5;125(3):411-4. Pubmed PMID: 16678083
- Li X, Lonard DM, Jung SY, Malovannaya A, Feng Q, Qin J, Tsai SY, Tsai MJ, O'Malley BW "The SRC-3/AIB1 coactivator is degraded in a ubiquitin- and ATP-independent manner by the REGgamma proteasome.." Cell. 2006 Jan 27;124(2):381-92. Pubmed PMID: 16439211
- Li C, Ao J, Fu J, Lee DF, Xu J, Lonard D, O'Malley BW "Tumor-suppressor role for the SPOP ubiquitin ligase in signal-dependent proteolysis of the oncogenic co-activator SRC-3/AIB1.." Oncogene. 2011 Oct 20;30(42):4350-64. Pubmed PMID: 21577200
- Li X, Amazit L, Long W, Lonard DM, Monaco JJ, O'Malley BW "Ubiquitin- and ATP-independent proteolytic turnover of p21 by the REGgamma-proteasome pathway.." Mol. Cell. 2007 Jun 22;26(6):831-42. Pubmed PMID: 17588518
Funding
- Small molecule SRC-2 antagonists as regulators of Sertoli cell function and male fertility - #5U01HD076596
- $219,100.00 (08/24/2012 - 06/30/2017) Grant funding from NIH
- The goal of this study is to identify and develop small molecule antagonist capable of inhibiting SRC-2 for their use as male contraceptive agents
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