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.
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.
- Autoimmune Disease
- Cancer Immunotherapy
- Mucosal immunology