Laura A Solt, PhD

Associate Professor
Department of Immunology and Microbiology
Florida Campus


 Email

Scripps Research Joint Appointments

Department of Molecular Medicine
Faculty, Graduate Program

Research Focus

The underlying theme of the research performed in the Solt laboratory is to understand the biologically relevant roles of nuclear receptors, a superfamily of ligand regulated transcription factors, in the immune system.  Our lab uses a combination of molecular biology, genetic, and chemical biology approaches coupled with mouse models of autoimmunity and chronic inflammation to study how different nuclear receptors’ expression, function, and activity affects disease.  As ligand-regulated transcription factors, nuclear receptors are excellent therapeutic targets for the treatment of a variety of diseases.  Therefore, we also work in collaboration with medicinal chemists to develop small molecule ligands to these receptors to further probe their function in vitro and in vivo.  Each receptor is unique and can have ligand- and/or tissue-specific effects.  Thus, we aim to gain a better understanding of nuclear receptor activity in tissue and disease-specific contexts to determine their therapeutic potential and for more rational drug design.


Education

Ph.D. (Immunology), University of Pennsylvania, 2008
B.S. (Psychology), Boston College, 1998

Professional Experience

2017-2018 Assistant Professor, Immunology and Microbiology, Scripps Research
2013-2017 Assistant Professor, Molecular Therapeutics, Scripps Research
2009-2013 Postdoctoral Fellow, Scripps Research

Awards & Professional Activities

Ruth L. Kirschstein National Research Service Awards, NIH (2010-2013)

Selected References

All Publications

Doebelin C, He Y, Campbell S, Nuhant P, Kumar N, Koenig M, Garcia-Ordonez R, Chang MR, Roush WR, Lin L, Kahn S, Cameron MD, Griffin PR, Solt LA, Kamenecka TM. Discovery and optimization of a series of sulfonamide inverse agonists for the retinoic acid receptor-related receptor-α. Med Chem2019 Feb 22;doi: 10.2174/1573406415666190222124745. [Epub ahead of print] 

Amir M, Chaudhari S, Wang R, Campbell S, Mosure SA, Chopp LB, Lu Q, Shang J, Pelletier OB, He Y, Doebelin C, Cameron MD, Kojetin DJ, Kamenecka TM, Solt LAREV-ERBα Regulates TH17 Cell Development and Autoimmunity. Cell Rep2018 Dec 26;25(13):3733-3749.e8.

Doebelin C, Patouret R, Garcia-Ordonez RD, Chang MR, Dharmarajan V, Novick S, Ciesla A, Campbell S, Solt LA, Griffin PR, Kamenecka TM. Identification of potent RORβ modulators: Scaffold variation. Bioorg Med Chem Lett2018 Oct 15;28(19):3210-3215.

Zhao J, Zhang L, Mu X, Doebelin C, Nguyen W, Wallace C, Reay DP, McGowan SJ, Corbo L, Clemens PR, Wilson GM, Watkins SC, Solt LA, Cameron MD, Huard J, Niedernhofer LJ, Kamenecka TM, Robbins PD. Development of novel NEMO-binding domain mimetics for inhibiting IKK/NF-κB activation. PLoS Biol2018 Jun;16(6):e2004663

Amador A, Campbell S, Kazantzis M, Lan G, Burris TP, Solt LADistinct roles for REV-ERBα and REV-ERBβ in oxidative capacity and mitochondrial biogenesis in skeletal muscle. PLoS One2018;13(5):e0196787.

Amador A, Kamenecka TM, Solt LA, Burris TP. REV-ERBβ is required to maintain normal wakefulness and the wake-inducing effect of dual REV-ERB agonist SR9009. Biochem Pharmacol2018 Apr;150:1-8

Sun Y, Liu CH, Wang Z, Meng SS, Burnim SB, SanGiovanni JP, Kamenecka TM, Solt LA, Chen J. RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis. FASEB J2017 Oct;31(10):4492-4502.

Amador A, Huitron-Resendiz S, Roberts AJ, Kamenecka TM, Solt LA, Burris TP. Pharmacological Targeting the REV-ERBs in Sleep/Wake Regulation. PLoS One2016;11(9):e0162452

de Vera IM, Giri PK, Munoz-Tello P, Brust R, Fuhrmann J, Matta-Camacho E, Shang J, Campbell S, Wilson HD, Granados J, Gardner WJ Jr, Creamer TP, Solt LA, Kojetin DJ. Identification of a Binding Site for Unsaturated Fatty Acids in the Orphan Nuclear Receptor Nurr1. ACS Chem Biol2016 Jul 15;11(7):1795-9

Amador A, Wang Y, Banerjee S, Kamenecka TM, Solt LA, Burris TP. Correction: Pharmacological and Genetic Modulation of REV-ERB Activity and Expression Affects Orexigenic Gene Expression. PLoS One2016;11(5):e0156367

Wang R, Solt LA. Metabolism of murine TH 17 cells: Impact on cell fate and function. Eur J Immunol2016 Apr;46(4):807-16.

Amador A, Wang Y, Banerjee S, Kameneka TM, Solt LA, Burris TP. Pharmacological and Genetic Modulation of REV-ERB Activity and Expression Affects Orexigenic Gene Expression. PLoS One2016;11(3):e0151014

Sun Y, Liu CH, SanGiovanni JP, Evans LP, Tian KT, Zhang B, Stahl A, Pu WT, Kamenecka TM, Solt LA, Chen J. Nuclear receptor RORα regulates pathologic retinal angiogenesis by modulating SOCS3-dependent inflammation. Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10401-6.

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

Sitaula S, Billon C, Kamenecka TM, Solt LA, Burris TP. Suppression of atherosclerosis by synthetic REV-ERB agonist. Biochem Biophys Res Commun. 2015 May 8;460(3):566-71.

Solt LA, Banerjee S, Campbell S, Kamenecka TM, Burris TP. ROR inverse agonist suppresses insulitis and prevents hyperglycemia in a mouse model of type 1 diabetes. Endocrinology. 2015 Mar;156(3):869-81.

Banerjee S, Wang Y, Solt LA, Griffett K, Kazantzis M, Amador A, El-Gendy BM, Huitron-Resendiz S, Roberts AJ, Shin Y, Kamenecka TM, Burris TP. Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour. Nat Commun. 2014 Dec 23;5:5759.

Matta-Camacho E, Banerjee S, Hughes TS, Solt LA, Wang Y, Burris TP, Kojetin DJ. Structure of REV-ERBβ ligand-binding domain bound to a porphyrin antagonist. J Biol Chem. 2014 Jul 18;289(29):20054-66.

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. Rev-erb-α modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy. Nat Med. 2013 Aug;19(8):1039-46.

Griffett K, Solt LA, El-Gendy Bel-D, Kamenecka TM, Burris TP. A liver-selective LXR inverse agonist that suppresses hepatic steatosis. ACS Chem Biol. 2013 Mar 15;8(3):559-67.

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

Kumar N, Lyda B, Chang MR, Lauer JL, Solt LA, Burris TP, Kamenecka TM and Griffin PR. Identification of SR2211: A Potent Synthetic RORγ-Selective Modulator. ACS Chem Biol. 2012 Apr 20;7(4):672-7.

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 and  Burris TP.  Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists.  Nature. 2012; Mar 29; 485 (7396): 62-8. 

Doerdelmann T, Kojetin DJ, Baird-Titus JM, Solt LA, Burris TP, Rance M. Structural and biophysical insights into the ligand-free Pitx2 homeodomain and a ring dermoid of the cornea inducing homeodomain mutant. Biochemistry. 2012 Jan 17;51(2):665-76.

Wang Y, Solt LA, Kojetin DJ, Burris TP. Regulation of p53 stability and apoptosis by a ROR agonist. PLoS One. 2012;7(4):e34921.

Solt LA, Kamenecka TM and Burris TP.  LXR-Mediated Inhibition of CD4+ T Helper Cells. PLoS One. 2012; 7(9):e46615.

Solt LA, Kumar N, He Y, Kamenecka TM, Griffin PR and Burris TP. Identification of a Selective RORγ Ligand that Suppresses TH17 cells and Stimulates T Regulatory CellsACS Chem Biol. 2012; 7(9): 1515-9.

Solt LA and Burris TP.  Action of RORs and Their Ligands in (patho) Physiology. Trends Endocrinol Metab. 2012; 23(12): 619-27.

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 and Burris TP.  Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand.  Nature. 2011 Apr 28; 472 (7344): 491-4.                     

Solt LA, Kojetin DJ and Burris TP. The REV-ERBs and RORs: molecular links between circadian rhythms and lipid homeostasis. Future Med Chem. 2011 Apr; 3 (5): 623-38.

Kumar N, Kojetin DJ, Solt LA, Kumar KG, Nuhant P, Duckett DR, Cameron MD, Butler AA, Roush WR, Griffin PR and Burris TP.  Identification of SR3335 (ML-176): A Synthetic RORα Selective Inverse Agonist. ACS Chem Biol. 2011 Mar 18; 6 (3): 218-22.

Begriche K1, Levasseur PR, Zhang J, Rossi J, Skorupa D, Solt LA, Young B, Burris TP, Marks DL, Mynatt RL, Butler AA. Genetic dissection of the functions of the melanocortin-3 receptor, a seven-transmembrane G-protein-coupled receptor, suggests roles for central and peripheral receptors in energy homeostasis. J Biol Chem. 2011;286(47):40771-81.

Kumar N, Solt LA, Wang Y, Rogers PM, Bhattacharyya G, Kamenecka TM, Stayrook KR, Crumbley C, Floyd ZE, Gimble JM, Griffin PR and Burris TP. Regulation of adipogenesis by natural and synthetic REV-ERB ligands. Endocrinology. 2010 July;151(7):3015-25.

Wang YJ, Solt LA, Burris TP. Regulation of FGF21 Expression and Secretion by Retinoic Acid Receptor-Related Orphan Receptor alpha.  J. Biol. Chem.  2010.  May 21: 285 (21): 15668-73.

Kumar N, Solt LA, Conkright JJ, Wang Y, Istrate MA, Busby SA, Garcia-Ordonez R, Burris TP and Griffin PR.  The benzenesulfoamide T0901317 is a novel RORα/γ Inverse Agonist. Mol. Pharm. 2010. 77(2): 228-36.

Wang Y, Kumar N, Solt LA, Richardson TI, Helvering LM, Crumbley C, Garcia-Ordonez RA, Stayrook KR, Zhang X, Novick S, Chalmers MJ, Griffin PR and Burris TP. Modulation of RORα and RORγ activity by 7-oxygenated sterol ligands. J. Bio.Chem.  2010. 285 (7): 5013-25.

Solt LA, Griffin PR and Burris TP. Ligand Regulation of Retinoic Acid Receptor-Related Orphan Receptors (RORs): Implications for Development of Novel Therapeutics.  Curr. Opin. Lipidol. 2010. 21 (3): 204-11.


Links

Complete List of Citations