Protein whisperer Oluwatoyin Asojo fights neglected diseases

When Oluwatoyin Asojo was about 9 years old, she started volunteering regularly at an orphanage near where she lived in Nigeria. She remembers seeing kids infected with parasitic worms, or with faces disfigured from leprosy.

“It was eye-opening,” Asojo says. She was raised on campus at one of Africa’s finest universities and Nigeria’s oldest — the University of Ibadan. Her mother was a schoolteacher, and her father ran teaching labs and his own anatomy and histology lab, where Asojo helped out as a kid. A published poet in high school, she hobnobbed with famous bards at the Ibadan poetry club. “You just realize just how blessed you are, living in this little cocoon,” she says.

Helping those without her privilege became the driving force behind Asojo’s career. Today, she has dual roles. As an expert in puzzling out protein structures, she’s taken on proteins involved in diseases that disproportionately affect people in some of the world’s poorest regions. Think malaria, HIV and, Asojo’s specialty, scourges the research establishment typically overlooks, including leishmaniasis and schistosomiasis. Notably, she’s contributed to vaccines being tested in people to prevent hookworm — a parasite she encountered in the orphanage.

In her second role as a university leader, she’s guided scores of students from communities that are traditionally underrepresented in science. Last year, she left a chair position at Hampton University in Virginia to become the associate director of strategic initiatives at Dartmouth Cancer Center.

A passion for proteins

Young Asojo wanted to do something about diseases, but despite her parents’ wishes, she didn’t think medical school would be a good fit. She left Nigeria on a scholarship at 16, moving to Canada and then Texas for higher education. At the University of Houston, where she got a Ph.D. in chemistry, watching proteins form solid crystals enraptured her. “It was like, ‘Whoa, this is so beautiful.’”

In a technique called X-ray crystallography, scientists can use the crystallized form of a protein or other molecule to determine the 3-D layout of its atoms. Through two postdoctoral fellowships and a job at a pharmaceutical company during the late 1990s and early 2000s, Asojo mastered the technique.

Drugmakers use crystallography to understand the proteins involved in disease, including those essential for parasite survival and for viral entry into cells. Those protein structures can guide the development medications or vaccines. But Asojo encountered few researchers applying crystallography to the illnesses she saw in the orphanage. Here, then, was her chance. 

In 2002, while conducting postdoctoral work, Asojo began collaborating with the Human Hookworm Vaccine Initiative, an international, multi-institution effort funded in part by the Gates Foundation. She continued that work as she launched her own research investigations at the University of Nebraska Medical Center in Omaha.

Hookworm as parasitic adversary

Hookworm affects up to an estimated 740 million people. Most live in sub-Saharan Africa, Asia and Latin America, though pockets of infections exist in the United States. Humans and other animals get infected by coming into contact with soil containing hookworm larvae. The parasites penetrate the skin and migrate to the gut, where they feed on blood. Infected people may lose weight or have diarrhea or anemia. They pass eggs in their feces, starting the cycle anew. Medications don’t always work and repeat infections are common.

As a crystallographer at Nebraska and then Baylor College of Medicine in Houston, Asojo applied her skills to the challenge of a hookworm vaccine. By 2005, she’d solved her first hookworm protein structure — for Na-ASP-2, a protein that the worm’s larvae emit. The protein, whose structure Asojo and colleagues reported in the Journal of Molecular Biology, would become the active component of a vaccine tested in human clinical trials. She also contributed to a report describing how to mass-produce and purify the protein, precursor steps to crystallography and essential to ensuring a reliable supply of vaccine for testing.

Asojo went on to solve four more hookworm protein structures. They offered details on how the proteins themselves might interact with the human immune system on a molecular level. In at least one case, her structure provided clues to a protein’s role in the parasite’s survival, important information for developing vaccines or medications.

Crystallography is arduous work, says Hampton University protein biochemist Graham Chakafana, a collaborator and mentee of Asojo’s. To get a structure, in addition to mass production and purification, a scientist must coax a protein to form crystals by trying a slew of chemical additives. Sometimes only one or two of those steps works, he says. “Imagine how devastating it is, because you might get to the middle and then fail.”

If anyone can power through all that, Chakafana says, it’s Asojo. “She is very driven and she’s not someone who gives up.” 

Asojo attributes her persistence to her upbringing. “People gave me the freedom to mess up,” she says, and it taught her something: “Failure does not reflect on my intelligence. Failure just means I learned.”

Asojo’s philosophy was tested in 2012, when researchers reported that the experimental Na-ASP-2 hookworm vaccine caused hives in Brazilian volunteers. The setback prompted a pivot to other vaccine candidates still in development. They contain other proteins Asojo also worked on. “It’s not about if the project fails,” she says. “It’s, did we learn enough?”

A leader and role model

By 2018, Asojo was eager to grow in a new role. In mentoring students for well over a decade, she’d noticed that many of her mentees from historically Black colleges and universities, or HBCUs, weren’t given the same preparation for research as counterparts at other schools. “I wanted to work full time with students and junior faculty to catalyze their success,” she says.

She moved to Hampton, an HBCU, where she became chemistry and biochemistry department chair in 2019. Her focus shifted from doing her own research to training new researchers. She secured funding to test ways to help Black students stay in courses with high dropout rates, like first-year chemistry. Another grant funded development of a curriculum that prepares Hampton’s most ambitious scholars to enroll in ultracompetitive Ph.D. and M.D./Ph.D. programs. A third upgraded Hampton’s research infrastructure with an X-ray instrument.  

Her move to Dartmouth Cancer Center last August is a natural progression of that work. She’s eager to not only grow as a researcher but also recruit and retain students and early-career faculty from groups that tend to be underrepresented in the sciences.

The trajectory of one student, named Jeremy Young, suggests that won’t be new. At Hampton, Young lost a merit scholarship because a more-challenging-than-usual course-load caused him to just miss a GPA requirement. Asojo helped him find other funding to support his education. Today he’s just begun graduate school at the Johns Hopkins University School of Medicine. 

“​​I’m a first generation college student, and I didn’t really have anybody who looked like me who was a chemist or a scientist,” Young says. “I still owe my budding scientific career and the future career that I have in science to Dr. Asojo, because of how impactful she was for me in that moment.”