Denise Okafor received her B.S. in biomedical chemistry from Oral Roberts University. She earned an M.S. in chemistry and a Ph.D. in biochemistry at Georgia Institute of Technology. Her dissertation research was focused on the metallobiochemistry of RNA, investigating RNA folding and function as mediated by divalent cations magnesium and iron. Her postdoctoral research in the Ortlund lab at Emory University was focused on nuclear receptors, a family of ligand-regulated transcription factors. She used molecular dynamics simulations to investigate the mechanisms underlying ligand activation in nuclear receptors. As an NIH-IRACDA postdoctoral fellow, Denise also taught at Morehouse and Spelman colleges in Atlanta.
Denise Okafor
Penn State
Assistant Professor of Biochemistry and Molecular Biology and ChemistryTalk: "Architectural Plasticity and Allostery in Nuclear Receptors"
Nuclear receptors are ligand-regulated transcription factors that controls genes important for metabolism, development and reproduction. While nuclear receptor activity depends on coordinated communication across multiple domains, the ways that allosteric signals propagate across full-length nuclear receptor architectures remains poorly understood. Using the farnesoid X receptor (FXR) as a model, we investigate how ligands and DNA shape multidomain organization. Through computational modeling and molecular dynamics simulations, we show that ligands selectively induce domain rearrangement in FXR, promoting interdomain contact which we validate experimentally. Further, we uncover a new DNA-induced quaternary architecture of FXR, showing that it binds DNA as a homodimer, adopting a uniquely extended conformation that is distinct from the canonical form observed in the heterodimer. Together, these studies reveal that architectural allostery, governed by ligand and DNA binding, is a fundamental principle of nuclear receptor regulation.cdo5093@psu.edu