Visibility in Mentorship: Spotlight on Anthony Nicola
It was during Nicola’s undergraduate studies in biology at Drew University in New Jersey that he began to pursue his interest in science, first through the UMDNJ-New Jersey Medical School Summer Undergraduate Research Program (now Rutgers-Newark). “I was bitten by the bug,” he recalled. “I was fascinated by the approach to answering scientific questions.”
For early-career scientists who were also “bitten by the bug,” Nicola advises students to find mentors who remind them to embrace challenges as well as celebrate and take pride in successes. Nicola also encourages mentors to remind students that just because others may make something look easy, doesn’t mean that it is. “We need to invite young scientists in at the ground floor to the process of scientific publication, navigating the funding system early on and sharing with them the process and what we go through on a regular basis,” he added. This, he noted, is vital for addressing and combating imposter syndrome. Nicola’s career trajectory would ultimately inform this advice.
After earning his B.A. in biology in 1991, Nicola went on to the University of Pennsylvania for his graduate studies, where he worked alongside Roselyn Eisenberg, Ph.D. and Gary Cohen, Ph.D., both of whom are renowned experts in the field of herpesvirus entry. His thesis would eventually focus on a structure-function analysis of the herpes simplex virus (HSV) receptor-binding glycoprotein D (gD). Following his Ph.D. (1996), Nicola continued as a postdoctoral researcher in the lab of Ari Helenius, Ph.D., at Yale University School of Medicine. When Helenius moved his lab to ETH Zurich in Switzerland, Nicola followed. There, he spent 2 years researching the cell biology of protein folding in the cytosol of eukaryotes and prokaryotes using a model alphavirus protein.
“There's still no approved vaccine for HSV, and there's still no cure—herpesvirus infections are lifelong. For most, infection is asymptomatic. But for others, HSV can be very distressing. It's an important sexually transmitted infection (STI), causing genital ulcers,” he explained. “In rare cases, HSV can cause severe outcomes, such as neonatal infection, encephalitis and blindness. So, understanding how the virus infects cells and the resulting immune response to the virus is critical for developing therapeutics—both vaccines, as well as new antiviral drugs.”
After completing his postdoctoral research, Nicola moved to Washington, D.C. in 1999 to start a research fellow position at the National Institutes of Health (NIH), Bethesda, Maryland. He trained with Stephen Straus, M.D., who served as an important mentor for Nicola. “He gave me a tremendous opportunity, a lot of leeway and a lot of space to pursue my own [scientific] interests, which I realize now was pretty rare,” Nicola said. “Dr. Straus held his trainees to high accountability, but also gave them space to explore.” It was through this experience that Nicola and the team made the seminal finding that herpesviruses can use low pH cellular entry pathways.
“It had been scientific dogma for decades that HSV, the human pathogen, was considered a paradigm for viruses that fuse directly [to] the plasma membrane,” Nicola explained. “We had shown that, while that does happen, the virus also enters physiologically relevant cells by endocytosis. And it’s the low pH milieu of the endosomes that can trigger fusion of HSV with the limiting membrane of the endosome, resulting in entry.” Specifically, the team's model indicated that the virus first infects skin epithelial cells by a low pH-dependent (i.e., acidic) pathway and, subsequently, infects peripheral neurons—where the virus lives during periods of latency—by direct penetration at the plasma membrane. This discovery “was something that a lot of folks in the field were not ready for,” Nicola said.
While the discovery was met with some resistance, as it countered previous conclusions, Nicola says the team was fortunate to not have to wait for an entire generation to pass before it became widely accepted that herpesviruses do indeed take multiple cellular entry pathways, depending on the cell type.
“That finding while I was at NIH really launched and has shaped my career to this day,” he said. “We've spent the intervening years dissecting out exactly how this [process] works, and why the virus chooses a different pathway [depending on cell type].” Nicola recounted that initially he thought selection of entry pathway would be straightforward, that specific cell surface receptors on epithelial cells or neurons would dictate which entry route is taken. “Receptors are important, but they're not the whole story. It's a complex interplay of viral and cell determinants that help the virus decide how to enter the cell.” As an example, the viral envelope protein gC selectively facilitates epithelial cell entry.
After 5 years at NIH, Nicola received a Research Scholar Development Award from the National Institute of Allergy and Infectious Diseases (NIAID) and started his first faculty position at Virginia Commonwealth University. In 2011, he decided to move his lab across the country to WSU. To this day, Nicola’s research continues to focus on herpesviruses, including veterinary alphaherpesviruses, and his team has begun to understand more about the molecular basis of why herpesviruses utilize low pH to enter certain cell types. Intracellular low pH activates the viral fusion glycoprotein B (gB). The team identified low pH-triggered conformational changes in HSV gB that they believe are critical for its membrane fusion function. Nicola added that his lab has also worked to define additional cellular and viral determinants of entry.
Nicola has trained more than 10 Ph.D. students and is an elected fellow of the American Association for the Advancement of Science. He serves on the editorial board of the ASM journal, Journal of Virology, and is the herpesvirus editor for Viruses. In recent years, Nicola has enjoyed taking on administrative positions, such as interim department chair and the director of WSU’s infectious diseases graduate program. He also currently serves on the council of the American Society for Virology.
“[Leadership positions] have been very rewarding in different ways—to shape the future of programs, and to materially help populations that you care very much about,” he said. “Mentoring both graduate students and junior faculty is a passion of mine. When you're in academia, there's the 3-legged stool of teaching, research and service. And I've been fortunate to participate in service activities that mean a lot to me.” Nicola founded the junior faculty mentoring program in his department that has seen more than 12 faculty through the tenure and/or promotion process. In 2018, he was recognized as an Exceptional Mentor by the Achievement Awards for College Scientists (ARCS) organization.
When reflecting on mentorship in the microbial sciences, Nicola emphasized the importance of early-career individuals being able to see themselves as scientists, as reflected by a diverse scientific workforce and the mentors they look up to.
“It's crucial to have mentors that understand where you're coming from and your background. The culture of academia and academic science isn't always intuitive. I was a first-generation college student and first-generation Ph.D. student and faculty member. There's a lot that you're expected to navigate on your own,” he explained. “Mentors and colleagues that have had similar experiences to you can help you navigate situations. Whereas you may have peers that come from different backgrounds that may have a leg up for 1 reason or another. Diversity in the scientific workplace is so important, as well as visibility of diverse scientists.”
As a member of the LGBTQIA+ community, Nicola noted that visibility has come a long way since he first entered the profession of microbiology. Still, he said there is work to be done, and campaigns like 500 Queer Scientists aim to boost visibility for LGBTQIA+ folks in STEM, as well as connect scientists with resources and potential mentors. “It really is a window for young scientists so they can say, ‘Hey, there are a lot of people out there like me who are thriving in this environment and who are doing great science.’”
At WSU, Nicola serves on the President's Commission for Gender Identity/Expression and Sexual Orientation. The commission brings together administrators, faculty, staff and students from across the university system (with multiple campuses in Washington State), with the mission of advising the university administration on issues pertaining to the LGBTQIA+ community. Additionally, the commission launched a pilot program for mentoring new staff and faculty as they onboard at WSU. Both students and employees at the university can access resources or ask questions through the commission’s website about anything from health care and childcare to promotion and tenure.
"Mentoring is critical for recruitment and retention of the scientific workforce at all levels—undergraduates, graduates, graduate students, postdocs, staff scientists and faculty,” Nicola said. “The advice I always give folks is to actively seek out the mentoring that you need. We all should maintain networks, formal and informal mentors throughout our careers. You never stop needing mentoring.”
