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Biophysicist in Profile

Denise Okafor

Denise Okafor

April 2021 // 3491

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, 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 quan­tum 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 mas­ter’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 chal­lenges 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 recep­tors.

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 hor­mone 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 effec­tive 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 assis­tant 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 binding domain,” she explains. “The mechanisms by which these two domains coordinate to achieve ligand-specific tran­scriptional outcomes is poorly understood. Small changes in ligand structure will often lead to large, unintuitive changes in transcriptional activity. The goal of my lab is to combine mo­lecular dynamic simulations with biophysical and biochemical experiments to understand how ligands achieve transcrip­tional control in nuclear receptors.”

Tracy Hei Yan Yu was the first graduate student to join Okafor’s lab at Penn State. “Our lab studies allosteric signal­ing in nuclear receptors. And my project is to investigate the mechanisms of allosteric regulation in Farnesoid X receptor, using a variety of biochemical, biophysical, and computational methods. In particular, I am interested in studying how ligand structure, coregulator recruitment and promoter specificity contribute to allosteric regulation in Farnesoid X receptor,” she says. “The most memorable quality of Denise is that she makes you feel like you are not alone (and this is the major reason that I joined the lab). I have had this feeling since I rotated with her. There was nothing established in the lab, and I was the first student to start setting up the equipment and doing some simple experiments. She was always there working with me. Even though we have more people working in the lab now and she is very busy with her work and a new­born baby, she is always approachable and willing to help you when you have any struggles.”

The most rewarding aspect of her career is seeing her ideas attempted successfully. “All the ideas do not always work as anticipated, but it is a rush like no other when they do. A close second for me has been seeing the members of my lab (postdocs and students) adopt the research ideas I have put forward, develop their own passion for the questions and drive the work forward. It has been very rewarding to see them put their own spin on the research ideas and it gets me excited about the potential we have to contribute meaningful­ly to the field.”

Okafor has very clearly seen the importance of mentoring in her own career, so her advice to those just starting out in biophysics is to seek out good mentors. “They can really make all the difference. You want people who will be responsive and unselfish in their mentoring. And you should also look to pay this mentoring forward to younger scientists,” she says. “Don’t be resistant to unsolicited advice, because you don’t know what you don’t know. Instead, run it all through your judgment filters, save the advice that is valuable and toss the rest. Finally, I would say try to stay focused. Biophysics is a broad field that provides a nearly overwhelming wealth of tools to answer any given question. I’m learning that it is important to stay focused on my scientific goals and try to not get distracted by the latest, flashiest thing. But this also applies to focusing on our own careers: it is very easy, but also very unproductive to compare our paths to other people’s. Stay focused.”

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