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Welcome to the Solt Lab

Research Focus

Nuclear receptors (NR) are an evolutionarily conserved family of ligand-regulated transcription factors that have been demonstrated to regulate a host of physiological processes, including development, reproduction, metabolism, and immune responses. Our group's focus is to use a combination of genetic, molecular biology, and chemical biology approaches to better understand NRs roles in vivo in the context of various diseases. Ultimately, we aim to identify and develop small molecule modulators of NRs for the therapeutic treatment of autoimmune and metabolic disorders.

NRs in Autoimmunity

An organism's immune system is a complex network of biological structures, processes, and cell types that has evolved to protect from foreign agents and the damage they may cause while sparing self-tissue. The failure of an organism to properly distinguish between "self" and "non-self" generates an autoimmune response. While the distinct mechanisms by which the body maintains tolerance to self-tissues has yet to be fully elucidated, recent findings have delineated novel cell types that provoke or protect from autoimmune pathology.

TH17 cells are a more recently identified lineage of CD4+ T helper cells that have been demonstrated to mediate autoimmune pathology. Several factors critical for the development of TH17 cells have been elucidated, including the orphan nuclear receptors (NRs), retinoic acid receptor-related orphan receptors a and g (RORa and RORgt). Our lab has identified other NRs that play key roles in regulating TH17 cell development and autoimmunity. Since NRs, including RORa and RORg, are ligand dependent transcription factors, an attractive strategy for the development of novel therapeutics aimed at TH17-mediated autoimmunity is the selective targeting of NRs responsible for TH17 cellular development and function. Other interests in the lab include understanding NRs roles in immune populations outside of TH17 cells.

NRs and Metabolic Diseases

Metabolism is the processes by which an organism obtains and makes energy from nutrient sources. Maintaining metabolic homeostasis is crucial for optimal health and dysregulation of various metabolic pathways can lead to disease states, including Type 2 diabetes and obesity. Through transcriptional control of gene networks, NRs have been demonstrated to play central roles in regulating metabolism in a tissue-specific manner. Altered signaling by NRs may cause an imbalance in metabolic homeostasis and contribute to pathogenesis of metabolic diseases. Therefore, selective targeting of various NRs may be an attractive strategy for the treatment of metabolic diseases.

    

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