Biophysical Society Bulletin | April 2021

Biophysicist in Profile

Denise Okafor Areas of Research

Institution Pennsylvania State University

Molecular dynamics simulations to investigate mechanisms of allosteric regulation in proteins


Denise Okafor grew up in a family that valued education. Her father was a businessman and her mother worked in personnel management, and both held master’s degrees, which helped inspire Okafor and her siblings to pursue advanced degrees. Though she planned to go to medical school, an undergraduate research opportunity spurred a change of course, and she set down the path toward her career as a research scientist.

Denise Okafor

Denise Okafor , assistant professor of biochemistry and molecular biology at Pennsylvania State University, was a biomedical chemistry major in college. There was not much opportunity for undergraduate research at her school, Oral Roberts University. She participated in a Research Experience for Undergraduates program during the summer following her junior year. “At the University of Memphis, I performed quan- tum mechanics calculations on supramolecular host-guest complexes. I found that I really enjoyed scientific research, and at the same time, my coursework helped me develop a deep love for chemistry. I made the choice to replace my premed aspirations with graduate school instead,” she shares. “The combination of my biochemical background with my limited computational research experience pushed me in the direction of computational biophysics in graduate school. I have not lost my love for this field ever since.” She went to Georgia Tech to pursue a graduate degree, where she faced the biggest challenge of her career. After failing the second attempt at her oral PhD candidacy exam, she was told that she should take courses to complete a mas- ter’s degree. She could not see a path forward. “In addition to being extremely discouraged, I had a hard time envisioning any other career. I think that when a person is at this point, it is very hard — if not impossible — for them to emerge from it without external validation. I was very fortunate to have good mentors in the department who served as this external voice for me, encouraging me to find a path to re-enroll in the PhD program and try again. While it was hard to get past such a huge setback (personally and academically), I kept these mentors close as I moved forward,” she shares. “In hindsight, the choice to push past those events and try again built a resiliency in me that I believe will last the rest of my academic career. A decade later, I can look back at the many other chal- lenges I’ve encountered since, and I realize that nothing I’ve dealt with since rivals that one challenging experience from graduate school.” This includes starting a new lab and having a baby in the same year as a global pandemic.

Following completion of her PhD, she joined the lab of Eric Ortlund at Emory University, where the focus was combining structural biology and biochemistry to study transcriptional signaling. Okafor used molecular dynamics simulations to investigate mechanisms of ligand regulation in nuclear recep- tors. Suzanne Mays was a PhD student in Ortlund’s lab when Okafor joined as a postdoc. “Denise has been one of my favorite people to work with, and we’ve been productive together. Our research in the Ortlund lab was focused on understanding how synthetic agonists activate a nuclear hor- mone receptor named LRH-1. Agonists of LRH-1 are highly sought as therapeutics for diseases such as type 2 diabetes, but it has been challenging to develop them due to a poor understanding of how LRH-1 responds to ligands to switch into the active state. We used an approach that combined X-ray crystallography and molecular dynamics simulations to study how different synthetic ligands interacted with LRH-1 and changed its conformation to activate the receptor. This work led to the development of more potent and effec- tive agonists,” Mays shares. “Even though we are not close geographically anymore, we are still working together a little. We are currently working on a computational project to study ligand-driven activation of LRH-1. Denise has an amazing focus and drive that I truly admire. Once she decided that she wanted to start her own lab, she moved swiftly and directly toward that goal. She is absolutely fearless in pursuit of her dreams.” In January 2020, Okafor started her own lab as an assis- tant professor of biochemistry and molecular biology at Pennsylvania State University. “The biggest focus in my lab is understanding how proteins — nuclear receptors in particular — are allosterically regulated. Nuclear receptors are ligand-regulated transcription factors. Ligands bind to the ligand binding domain of nuclear receptors, leading to allosteric (long-range) modulation of DNA binding at the DNA

March 2021



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