Laura Solt

Laura Solt, Ph.D.

Associate Professor

Department: SR-IM-SOLT LAB
Business Phone: (561) 228-2295
Business Email: lsolt1@ufl.edu

About Laura Solt

Laura A. Solt, Ph.D., is an Associate Professor in the Department of Immunology and Microbiology at Scripps Florida in Jupiter, Florida. She received her B.A. from Boston College and her Ph.D. in Immunology from the University of Pennsylvania. After completing her postdoctoral research at Scripps, she started her independent laboratory at Scripps Florida in 2013. Dr. Solt’s research is focused on understanding the biological roles of nuclear receptors in the immune system, with a specific focus on Th17 cells, and how their expression, function, and activity affects disease. Her lab uses a combination of molecular biology, genetic, and chemical biology approaches coupled with mouse models of autoimmunity and chronic inflammation to study the RORs, REV-ERBs, and NR2F6 either individually and/or cross-talk between the receptors. As ligand-regulated transcription factors, nuclear receptors function as excellent targets for the treatment of a variety of diseases. Therefore, we also work in close collaboration with medicinal chemists to design and develop small molecule ligands to these receptors to further probe their functions in vitro, in vivo, and to evaluate their therapeutic potential. Using these approaches, we described a negative regulatory role for the nuclear receptor REV-ERBa in Th17 cell development and autoimmunity. We also described the design and synthesis of newer, more potent synthetic REV-ERB modulators that target Th17 cells in vivo. Recently, we have extended our studies to better understand how heme, the REV-ERBs endogenous ligand, regulates REV-ERB activity in Th17 cells. Finally, we also described the design and synthesis of synthetic RORa modulators. We published a role for RORa in Th17 cells and the characterization of RORa-selective small molecules to target Th17 cells and treat Th17-mediated autoimmunity. Targeting the REV-ERBs or RORa demonstrate an alternative approach to the current design of RORgt modulators – of which many have entered clinical trials and failed for numerous reasons. Insight into the transcriptional regulation of nuclear receptors and their ligand(s) function is essential to comprehend the signaling pathways that govern Th17 cell homeostasis vs. pathogenicity as well as the rational design of therapeutics for specific disease indications.

Related Links:
Additional Positions:
Assistant Professor, Immunology and Microbiology
2017 – 2018 · Scripps Research
Assistant Professor, Molecular Therapeutics
2013 – 2017 · Scripps Research
Postdoctoral Fellow
2009 – 2013 · Scripps Research

Accomplishments

Ruth L. Kirschstein National Research Service Awards
2010-2013 · National Institutes of Health

Research Profile

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.

Open Researcher and Contributor ID (ORCID)

0000-0001-8807-0342

Areas of Interest
  • Autoimmune Disease
  • Cancer Immunotherapy
  • Immunometabolism
  • Mucosal immunology
  • Neuroimmunology

Publications

2022
A Compass to Guide Insights into TH17 Cellular Metabolism and Autoimmunity.
Immunometabolism. 4(1) [DOI] 10.20900/immunometab20220001. [PMID] 34900348.
2022
High throughput screening for compounds to the orphan nuclear receptor NR2F6.
SLAS discovery : advancing life sciences R & D. 27(4):242-248 [DOI] 10.1016/j.slasd.2022.03.005. [PMID] 35331960.
2022
REV-ERBα regulates age-related and oxidative stress-induced degeneration in retinal pigment epithelium via NRF2.
Redox biology. 51 [DOI] 10.1016/j.redox.2022.102261. [PMID] 35176707.
2022
Targeting Nuclear Receptors for TH17-Mediated Inflammation: REV-ERBerations of Circadian Rhythm and Metabolism.
Immunometabolism. 4(2) [DOI] 10.20900/immunometab20220006. [PMID] 35475255.
2021
CAR directs T cell adaptation to bile acids in the small intestine
Nature. 593(7857):147-151 [DOI] 10.1038/s41586-021-03421-6. [PMID] 33828301.
2021
Genetic and pharmacological inhibition of the nuclear receptor RORα regulates TH17 driven inflammatory disorders
Nature Communications. 12(1) [DOI] 10.1038/s41467-020-20385-9. [PMID] 33397953.
2021
Structural basis for heme-dependent NCoR binding to the transcriptional repressor REV-ERBβ.
Science advances. 7(5) [DOI] 10.1126/sciadv.abc6479. [PMID] 33571111.
2021
Uncovering New Challenges in Targeting Glycolysis to Treat Th17 Cell-Mediated Autoimmunity.
Immunometabolism. 3(1) [DOI] 10.20900/immunometab20210006. [PMID] 33614166.
2020
A molecular switch regulating transcriptional repression and activation of PPARγ.
Nature communications. 11(1) [DOI] 10.1038/s41467-020-14750-x. [PMID] 32075969.
2020
Pharmacological modulation and genetic deletion of REV-ERBα and REV-ERBβ regulates dendritic cell development.
Biochemical and biophysical research communications. 527(4):1000-1007 [DOI] 10.1016/j.bbrc.2020.05.012. [PMID] 32439175.
2019
Circadian rhythm-dependent and circadian rhythm-independent impacts of the molecular clock on type 3 innate lymphoid cells.
Science immunology. 4(40) [DOI] 10.1126/sciimmunol.aay7501. [PMID] 31586012.
2019
Discovery and Optimization of a Series of Sulfonamide Inverse Agonists for the Retinoic Acid Receptor-Related Orphan Receptor-α.
Medicinal chemistry (Shariqah (United Arab Emirates)). 15(6):676-684 [DOI] 10.2174/1573406415666190222124745. [PMID] 30799793.
2019
PGRMC2 is an intracellular haem chaperone critical for adipocyte function.
Nature. 576(7785):138-142 [DOI] 10.1038/s41586-019-1774-2. [PMID] 31748741.
2019
The nuclear receptor REV-ERBα modulates Th17 cell-mediated autoimmune disease.
Proceedings of the National Academy of Sciences of the United States of America. 116(37):18528-18536 [DOI] 10.1073/pnas.1907563116. [PMID] 31455731.
2018
Development of novel NEMO-binding domain mimetics for inhibiting IKK/NF-κB activation.
PLoS biology. 16(6) [DOI] 10.1371/journal.pbio.2004663. [PMID] 29889904.
2018
Distinct roles for REV-ERBα and REV-ERBβ in oxidative capacity and mitochondrial biogenesis in skeletal muscle
PLOS ONE. 13(5) [DOI] 10.1371/journal.pone.0196787. [PMID] 29723273.
2018
Identification of potent RORβ modulators: Scaffold variation.
Bioorganic & medicinal chemistry letters. 28(19):3210-3215 [DOI] 10.1016/j.bmcl.2018.08.017. [PMID] 30143422.
2018
REV-ERBα Regulates TH17 Cell Development and Autoimmunity.
Cell reports. 25(13):3733-3749.e8 [DOI] 10.1016/j.celrep.2018.11.101. [PMID] 30590045.
2018
REV-ERBβ is required to maintain normal wakefulness and the wake-inducing effect of dual REV-ERB agonist SR9009.
Biochemical pharmacology. 150:1-8 [DOI] 10.1016/j.bcp.2018.01.009. [PMID] 29355503.
2017
RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 31(10):4492-4502 [DOI] 10.1096/fj.201700172R. [PMID] 28646017.
2016
Correction: Pharmacological and Genetic Modulation of REV-ERB Activity and Expression Affects Orexigenic Gene Expression.
PloS one. 11(5) [DOI] 10.1371/journal.pone.0156367. [PMID] 27195801.
2016
Identification of a Binding Site for Unsaturated Fatty Acids in the Orphan Nuclear Receptor Nurr1.
ACS chemical biology. 11(7):1795-9 [DOI] 10.1021/acschembio.6b00037. [PMID] 27128111.
2016
Metabolism of murine TH 17 cells: Impact on cell fate and function.
European journal of immunology. 46(4):807-16 [DOI] 10.1002/eji.201545788. [PMID] 26893133.
2016
Pharmacological and Genetic Modulation of REV-ERB Activity and Expression Affects Orexigenic Gene Expression.
PloS one. 11(3) [DOI] 10.1371/journal.pone.0151014. [PMID] 26963516.
2016
Pharmacological Targeting the REV-ERBs in Sleep/Wake Regulation.
PloS one. 11(9) [DOI] 10.1371/journal.pone.0162452. [PMID] 27603791.
2015
Broad Anti-tumor Activity of a Small Molecule that Selectively Targets the Warburg Effect and Lipogenesis.
Cancer cell. 28(1):42-56 [DOI] 10.1016/j.ccell.2015.05.007. [PMID] 26120082.
2015
Nuclear receptor RORα regulates pathologic retinal angiogenesis by modulating SOCS3-dependent inflammation.
Proceedings of the National Academy of Sciences of the United States of America. 112(33):10401-6 [DOI] 10.1073/pnas.1504387112. [PMID] 26243880.
2015
ROR inverse agonist suppresses insulitis and prevents hyperglycemia in a mouse model of type 1 diabetes.
Endocrinology. 156(3):869-81 [DOI] 10.1210/en.2014-1677. [PMID] 25560829.
2015
Suppression of atherosclerosis by synthetic REV-ERB agonist.
Biochemical and biophysical research communications. 460(3):566-71 [DOI] 10.1016/j.bbrc.2015.03.070. [PMID] 25800870.
2015
Th17 cells in Type 1 diabetes: a future perspective.
Diabetes management (London, England). 5(4):247-250 [PMID] 27708719.
2014
Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour.
Nature communications. 5 [DOI] 10.1038/ncomms6759. [PMID] 25536025.
2014
Structure of REV-ERBβ ligand-binding domain bound to a porphyrin antagonist.
The Journal of biological chemistry. 289(29):20054-66 [DOI] 10.1074/jbc.M113.545111. [PMID] 24872411.
2013
A liver-selective LXR inverse agonist that suppresses hepatic steatosis.
ACS chemical biology. 8(3):559-67 [DOI] 10.1021/cb300541g. [PMID] 23237488.
2013
Nuclear receptors and their selective pharmacologic modulators.
Pharmacological reviews. 65(2):710-78 [DOI] 10.1124/pr.112.006833. [PMID] 23457206.
2013
Rev-erb-α modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy.
Nature medicine. 19(8):1039-46 [DOI] 10.1038/nm.3213. [PMID] 23852339.
2012
Action of RORs and their ligands in (patho)physiology.
Trends in endocrinology and metabolism: TEM. 23(12):619-27 [DOI] 10.1016/j.tem.2012.05.012. [PMID] 22789990.
2012
Identification of a selective RORγ ligand that suppresses T(H)17 cells and stimulates T regulatory cells.
ACS chemical biology. 7(9):1515-9 [PMID] 22769242.
2012
Identification of SR2211: a potent synthetic RORγ-selective modulator.
ACS chemical biology. 7(4):672-7 [DOI] 10.1021/cb200496y. [PMID] 22292739.
2012
LXR-mediated inhibition of CD4+ T helper cells.
PloS one. 7(9) [DOI] 10.1371/journal.pone.0046615. [PMID] 23029557.
2012
Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists.
Nature. 485(7396):62-8 [DOI] 10.1038/nature11030. [PMID] 22460951.
2012
Regulation of p53 stability and apoptosis by a ROR agonist.
PloS one. 7(4) [DOI] 10.1371/journal.pone.0034921. [PMID] 22509368.
2012
Structural and biophysical insights into the ligand-free Pitx2 homeodomain and a ring dermoid of the cornea inducing homeodomain mutant.
Biochemistry. 51(2):665-76 [DOI] 10.1021/bi201639x. [PMID] 22224469.
2011
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.
The Journal of biological chemistry. 286(47):40771-81 [DOI] 10.1074/jbc.M111.278374. [PMID] 21984834.
2011
Identification of SR3335 (ML-176): a synthetic RORα selective inverse agonist.
ACS chemical biology. 6(3):218-22 [DOI] 10.1021/cb1002762. [PMID] 21090593.
2011
Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand.
Nature. 472(7344):491-4 [DOI] 10.1038/nature10075. [PMID] 21499262.
2011
The REV-ERBs and RORs: molecular links between circadian rhythms and lipid homeostasis.
Future medicinal chemistry. 3(5):623-38 [DOI] 10.4155/fmc.11.9. [PMID] 21526899.
2010
Ligand regulation of retinoic acid receptor-related orphan receptors: implications for development of novel therapeutics.
Current opinion in lipidology. 21(3):204-11 [DOI] 10.1097/MOL.0b013e328338ca18. [PMID] 20463469.
2010
Modulation of retinoic acid receptor-related orphan receptor alpha and gamma activity by 7-oxygenated sterol ligands.
The Journal of biological chemistry. 285(7):5013-25 [DOI] 10.1074/jbc.M109.080614. [PMID] 19965867.
2010
Regulation of adipogenesis by natural and synthetic REV-ERB ligands.
Endocrinology. 151(7):3015-25 [DOI] 10.1210/en.2009-0800. [PMID] 20427485.
2010
Regulation of FGF21 expression and secretion by retinoic acid receptor-related orphan receptor alpha.
The Journal of biological chemistry. 285(21):15668-73 [DOI] 10.1074/jbc.M110.102160. [PMID] 20332535.
2010
The benzenesulfoamide T0901317 [N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-benzenesulfonamide] is a novel retinoic acid receptor-related orphan receptor-alpha/gamma inverse agonist.
Molecular pharmacology. 77(2):228-36 [DOI] 10.1124/mol.109.060905. [PMID] 19887649.
2007
Interleukin-1-induced NF-kappaB activation is NEMO-dependent but does not require IKKbeta.
The Journal of biological chemistry. 282(12):8724-33 [PMID] 17244613.

Grants

Sep 2022 ACTIVE
Tissue Selective Glucocorticoids
Role: Co-Investigator
Funding: NATL INST OF HLTH NIGMS
Jul 2022 ACTIVE
Identification of cellular heme transport receptors that regulate T cell function
Role: Principal Investigator
Funding: NATL INST OF HLTH NIAID
Apr 2022 ACTIVE
Identification of REV-ERB inverse agonists for cancer immunotherapy
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI
Apr 2022 ACTIVE
Elucidating the molecular mechanisms underlying ligand-dependent REV-ERB activity in Th17 cells
Role: Principal Investigator
Funding: NATL INST OF HLTH NIDDK
Apr 2022 – May 2022
Identification of Chemical Probes for the Orphan Nuclear Receptor NR2F6
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI

Education

Postdoctoral Fellow
2009-2013 · The Scripps Research Institute – Florida
Ph.D. in Immunology
2008 · University of Pennsylvania
Bachelor's of Science in Psychology
1998 · Boston College

Contact Details

Phones:
Business:
(561) 228-2295
Emails:
Business:
lsolt1@ufl.edu
Lab Admin Coordinator III:
Addresses:
Business Mailing:
Location C227
130 SCRIPPS WAY BLDG 3C1
JUPITER FL 33458