C. Denise Okafor

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.

Program or Departmental Affiliations

BMMB Graduate Program

The Department of Chemistry

Research Summary

We investigate structural mechanisms of signaling and regulation in protein complexes. We use MD simulations to determine how conformational dynamics of proteins are altered in different functional states. A broad range of biochemical and structural techniques are also employed. Combined, these allow us to carefully elucidate molecular mechanisms that govern the regulation of protein function. By understanding how proteins are regulated endogenously, we aim to identify novel strategies to selectively modulate protein function. Nuclear receptors are one of our favorite classes of molecules to study, because of the fascinatingly complex but elegant allosteric regulatory mechanisms that drive their function. They also play critical roles in metabolism, development, reproduction and other biological processes, which make them highly attractive therapeutic targets.

Honors and Awards

NIH Director's New Innovator Award, 2022

NSF CAREER Award, 2022

Kavli Fellow 2020

Keystone Symposia Fellow, 2019-2020

Burroughs Wellcome Fund Career Award at the Scientific Interface, 2018-2023

Ford Foundation Postdoctoral Fellowship, 2018 (declined)

Protein Society Hans Neurath Outstanding promise Travel Award, 2018

NIH-IRACDA Postdoctoral Fellow, 2015-2018

Selected Publications

Dube, N.; Khan, S.H., Sasse, R. and Okafor, C.D*. Identification of an Evolutionarily Conserved Allosteric Network in Steroid Receptors, Journal of Chemical Information and Modeling 2023. https://doi.org/10.1021/acs.jcim.2c01096

Khan, S.H.; Braet, S.M.; Koehler, S.J.; Elacqua, E.; Anand, G.S. and Okafor, C.D*. Ligand-induced shifts in conformational ensembles that describe transcriptional activation eLife 2022, 11:e80140 https://doi.org/10.7554/eLife.80140

Okafor, C.D.; Hercules, D.; Kell, S.A.; and Ortlund E.A. Rewiring ancient residue interaction networks drove the evolution of specificity in steroid receptors. Structure 2020

Okafor, C.D.; Colucci, J.K.; and Ortlund E.A. Ligand-Induced Allosteric Effects Governing SR Signaling. Nuclear Receptor Research 2019, 6.

Frank, F.F.; Okafor, C.D.; and Ortlund E.A. The first crystal structure of a DNA-free nuclear receptor DNA binding domain sheds light on DNA-driven allostery in the glucocorticoid receptor. Scientific Reports 2018, 8(1), 13497.

Okafor, C.D.; Pathak, M.F.; Fagan, C.E.; Bauer, N.C.; Cole, M.F.; Gaucher, E.A.; and Ortlund, E.A. Structural Analyses of Ancient, Modern and Consensus Elongation Factor TU proteins Reveal Strategies for Engineering Thermostability. Structure 2018, 26(1), 118-129.