Thomas P. Burris, Ph.D.

Adjunct Professor
Anesthesiology

Neurosciences Program
Biochemistry, Biophysics, and Structural Biology Program
Immunology Program

  • 314 446-8126

  • burristhomas@wustl.edu

  • Pharmacology and chemical biology of nuclear receptors.

Research Abstract:

My laboratory focuses on the pharmacology and chemical biology of nuclear receptors (NRs). Given the number of NRs that play a role in regulation of metabolic pathway, it is natural that my lab has been drawn to focus a number of projects in the area of diabetes and metabolic disease. I spent a decade working in the private pharmaceutical industry in drug discovery focused on NR targets and I brought this experience with me back to academia where I collaborate heavily with medicinal chemists and structural biologist to develop novel ligands for NRs that may hold utility in the treatment of diabetes/obesity. We developed the first synthetic ligands targeting REV-ERB that could be used in vivo and discovered that activation of this receptor led to substantially improved metabolic function via increased oxidative function in the skeletal muscle. We continue to examine these compounds as well as to improve their function toward a potential novel treatment for type 2 diabetes. We have developed high affinity agonists targeting the ERRs, which play a very important role in regulation of oxidative metabolism and mitochondrial biogenesis. Such compounds may have use in treatment of diseases such as diabetes and muscular dystrophy. My lab also developed the first RORgt targeted drugs that are now being used to target autoimmunity. Our work in regulation of the circadian rhythm and inflammation (REV-ERB, ROR and LXR) has led us to examined the potential utility of drugs we have developed for targeting Alzheimer`s disease. Finally, we continue to identify natural ligands for orphan nuclear receptors as well as develop synthetic ligands for such receptors that may have utility in treatment of human disease.

Selected Publications:

Recent Advances in the Medicinal Chemistry of Liver X Receptors.El-Gendy BEM, Goher SS, Hegazy LS, Arief MMH, Burris TP.J Med Chem. 2018 Jul 30. doi: 10.1021/acs.jmedchem.8b00045. [Epub ahead of print] PMID: 30004226

Therapeutic Effect of a Synthetic RORα/γ Agonist in an Animal Model of Autism.
Wang Y, Billon C, Walker JK, Burris TP .ACS Chem Neurosci. 2016 Feb 17;7(2):143-8. doi: 10.1021/acschemneuro.5b00159. Epub 2015 Dec 3.PMID: 26625251

Nuclear Receptor Subfamily 1 Group D Member 1 Regulates Circadian Activity of NLRP3 Inflammasome to Reduce the Severity of Fulminant Hepatitis in Mice.
Pourcet B, Zecchin M, Ferri L, Beauchamp J, Sitaula S, Billon C, Delhaye S, Vanhoutte J, Mayeuf-Louchart A, Thorel Q, Haas JT, Eeckhoute J, Dombrowicz D, Duhem C, Boulinguiez A, Lancel S, Sebti Y, Burris TP, Staels B, Duez HM. Gastroenterology. 2018 Apr;154(5):1449-1464.e20. doi: 10.1053/j.gastro.2017.12.019. Epub 2017 Dec 24. PMID: 29277561

REV-ERBα ameliorates heart failure through transcription repression.Zhang L, Zhang R, Tien CL, Chan RE, Sugi K, Fu C, Griffin AC, Shen Y, Burris TP, Liao X, Jain MK. JCI Insight. 2017 Sep 7;2(17). pii: 95177. doi: 10.1172/jci.insight.95177. [Epub ahead of print] PMID: 28878135

Broad Anti-tumor Activity of a Small Molecule that Selectively Targets the Warburg Effect and Lipogenesis.Flaveny CA, Griffett K, El-Gendy Bel-D, Kazantzis M, Sengupta M, Amelio AL, Chatterjee A, Walker J, Solt LA, Kamenecka TM, Burris TP .Cancer Cell. 2015 Jul 13;28(1):42-56. doi: 10.1016/j.ccell.2015.05.007. Epub 2015 Jun 25. PMID: 26120082 .

REV-ERB and ROR nuclear receptors as drug targets. Kojetin DJ, Burris TP. Nat Rev Drug Discov. 2014 Mar;13(3):197-216. doi: 10.1038/nrd4100. Review. PMID: 24577401

Rev-erb-α modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy. Woldt E, Sebti Y, Solt LA, Duhem C, Lancel S, Eeckhoute J, Hesselink MK, Paquet C, Delhaye S, Shin Y, Kamenecka TM, Schaart G, Lefebvre P, Nevière R, Burris TP, Schrauwen P, Staels B, Duez H. Nat Med. 2013 Aug;19(8):1039-46. doi: 10.1038/nm.3213. Epub 2013 Jul 14. PMID: 23852339

Nuclear receptors and their selective pharmacologic modulators. Burris TP, Solt LA, Wang Y, Crumbley C, Banerjee S, Griffett K, Lundasen T, Hughes T, Kojetin DJ. Pharmacol Rev. 2013 Mar 1;65(2):710-78. doi: 10.1124/pr.112.006833. Print 2013 Apr. Review. PMID: 23457206

Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists.
Solt LA, Wang Y, Banerjee S, Hughes T, Kojetin DJ, Lundasen T, Shin Y, Liu J, Cameron MD, Noel R, Yoo SH, Takahashi JS, Butler AA, Kamenecka TM, Burris TP.
Nature. 2012 Mar 29;485(7396):62-8. doi: 10.1038/nature11030. PMID: 22460951

Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand.
Solt LA, Kumar N, Nuhant P, Wang Y, Lauer JL, Liu J, Istrate MA, Kamenecka TM, Roush WR, Vidović D, Schürer SC, Xu J, Wagoner G, Drew PD, Griffin PR, Burris TP.
Nature. 2011 Apr 28;472(7344):491-4. doi: 10.1038/nature10075. Epub 2011 Apr 17.
PMID: 21499262

Last Updated: 8/21/2018 1:03:45 PM

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