- Role of Nuclear Receptors in Skeletal Development: (NIEHS). Exam the role of select NR’s to (dys)regulate critical gene regulatory networks governing mesenchymal stem cell recruitment, proliferation and terminal differentiation of skeletal cell lineages. This particular project focuses on how brominated and organophosphate flame retardants may modulate TR and PPAR transcriptional activities impacting MSC cell fate decisions. Additional studies are aimed at the role of AhR in MSC differentiation.
- Role of Vitamin D in Developmental Neurotoxicology and Obesity: (Supported by EPA STAR). Studies focus on defining linkages between aberant vitamin D/VDR signaling during early embryogenesis and adult onset and progression of neuraldegenerative disease and obesity.
- Evolution of the vitamin D receptor: (Supported by NSF). Studies examin how retention, loss or diversification of duplicate vitamin D receptor genes (VDRs) in teleosts have evolved new function(s) and/or partitioned ancestral functions in relation to endocrine innovations.
- Endocrine disrupting compounds (EDC):ER interactions: (Supported by NC Wildlife Commission). Investigate male reproductive toxicity through establishing functional roles of the estrogen receptor within defined cell types of the testis. Evaluate significance of EDC disruption in natitive NC sport fish populations.
- AhR Cardiovascular and development: (Supported though internal NCSU funds). Investigate mechanistic underpinnings of aryl hydrocarbon receptor (AhR) induced developmental toxicity. Focus-1: role of inflammation and eicosanoid pathways accociated with multifactorial congenital cardiovascular disease.
- Fate and effects of natural estrogens from CAFO’s: (Supported by EPA STAR). Develop a comprehensive quantitative relationships between the production, fate, transport and biological activity of endocrine active steroidal homones derived from Concentrated Animal Feeding Operations.
- In vivo screening for NR ligands and effect: (In collaboration with NIEHS/National Toxicology Program and Environmental Protection Agency). Develop the use of medaka and zebrafish as in vivo toxicity assays to validate in vitro Tox21 high throughput nuclear receptor chemical screens. We propose that use of small aquarium fish models in this context provides a rapid, inexpensive and efficient means to validate in vitro data in a living model that leverage the advantages of organismal complexity and extrapolation.
- Model Development-Hepatic Fibrosis: (Supported through NCSU-Center for Comparative Medicine and Translational Research). Establish a medaka model of dimethylnitrosamine-induced hepatic injury and fibrosis and investigated the role of the hepatic progenitor cells (HPC) in liver regeneration following chemically induce liver injury.