Investigating the role of nuclear receptors in cardio-metabolic diseases, diabetes complications, cancer, and inflammatory pain to develop novel tools and therapeutics.
Publications
2023
Thomas P. Burris, Ian Mitchelle S. de Vera, Isabelle Cote, Colin A. Flaveny, Udayanga S. Wanninayake, Arindam Chatterjee, John K. Walker, Nickolas Steinauer, Jinsong Zhang, Laurel A. Coons, Kenneth S. Korach, Derek W. Cain, Anthony N. Hollenberg, Paul Webb, Douglas Forrest, Anton M Jetten, Dean P. Edwards, Sandra L. Grimm, Sean Hartig, Carol A. Lange, Jennifer K. Richer, Carol A. Sartorius, Marc Tetel, Cyrielle Billon, Bahaa Elgendy, Lamees Hegazy, Kristine Griffett, Nahuel Peinetti, Kerry L Burnstein, Travis S. Hughes, Sadichha Sitaula, Keith R. Stayrook, Alexander Culver, Meghan H Murray, Brian N Finck and John A Cidlowski. (2023) International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily – Update 2023. Pharmacological Reviews August 16, 2023, PHARMREV-INR-2021-000436; DOI: https://doi.org/10.1124/pharmrev.121.000436
“The nuclear receptor (NR) superfamily comprises 48 transcription factors in humans that control a plethora of gene network programs involved in a wide range of physiological processes. In this review, we will summarize and discuss recent progress in NR biology and drug development derived from the integration of various approaches, including biophysical techniques, structural studies, and translational investigations. We also highlight how defective NR signaling results in various diseases and disorders and how NRs can be targeted for therapeutic intervention via modulation via binding to synthetic lipophilic ligands. Furthermore, we also review recent studies that improved our understanding of NR structure and signaling.”
“Nuclear receptors are ligand regulated transcription factors that function as key regulators of a wide range of physiological functions. NRs also serve as receptors for myriad drugs and in this review we provide an update of recent research into the function of this family of drug targets.”
“Pain is a complex problem affecting millions of people worldwide. The current therapies to reduce pain are limited as many treatment options inadequately address the causes of pain, lead to tolerance of the drug, or have adverse effects including abuse potential. While there are many causes of pain, one underlying mechanism to the pathogenesis and maintenance of pain conditions is chronic inflammation driven by the NLRP3 inflammasome. Several inflammasome inhibitors are currently under investigation however have the potential to suppress the functioning of the innate immune system, which may cause unwanted affects in patients. Here, we show that the nuclear receptor REV-ERB can suppress the activation of the inflammasome when pharmacologically activated with small molecule agonists. Additionally, REV-ERB activation appears to have analgesic potential in a model of acute inflammatory pain, likely as a result of inflammasome suppression.”
“Activation of LXR activity by synthetic agonists has been the focus of many drug discovery efforts with a focus on treatment of dyslipidemia and atherosclerosis. Many agonists have been developed, but all have been hindered due to their ability to efficaciously stimulate de novo lipogenesis. Here, we review the development of LXR inverse agonists that were originally optimized for their ability to enable recruitment of corepressors leading to silencing of genes that drive de novo lipogenesis. Such compounds have efficacy in animal models of MAFLD, dyslipidemia, and cancer. Several classes of LXR inverse agonists have been identified and one is now in clinical trials for treatment of severe dyslipidemia.”
doi: 10.3389/fmed.2023.1102469
A dual MTOR/NAD+ acting gerotherapy Jinmei Li, Sandeep Kumar, Kirill Miachin, Nicholas L. Bean, Ornella Halawi, Scott Lee, JiWoong Park, Tanya H. Pierre, Jin-Hui Hor, Shi-Yan Ng, Kelvin J. Wallace, NiklasRindtorff, Timothy M. Miller, Michael L. Niehoff, Susan A. Farr, Rolf F. Kletzien, JerryColca, Steven P. Tanis, Yana Chen, Kristine Griffett, Kyle S. McCommis, Brian N. Finck, Tim R. Peterson
Corresponding Author: Ryan M Teague, Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1100 South Grand Blvd, DRC Room 705, St. Louis, MO, 63104, United States. E-mail: ryan.teague@health.slu.edu
Griffett Lab 