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Spotlight on: Josephine Egan, senior investigator at NIA

NIA’s Josephine Egan, M.D., shares her COVID-19-related research and lessons learned about working in the lab during the pandemic.

During her more than 20 years at the National Institute on Aging (NIA), Senior Investigator Josephine Egan, M.D., has researched potential ways to intervene to prevent or slow age-related disability, conditions, and diseases, including diabetes. When SARS-CoV-2, the virus that causes COVID-19, took root in 2020, Egan, who is also chief of the NIA Laboratory of Clinical Investigation, quickly realized her lab’s repository of taste bud cells could be a significant and valuable resource in combating the disease.

Making a difference, one project at a time

As part of their recent research on taste receptor cells and taste stem cell function and how they differ with age and age-related diseases, Egan’s scientific team had already gathered a repository of taste papillae cells from the tongues of more than 100 people, 20 to 80 years of age. Papillae are the small bumps that cover the surface of the tongue. The team had cultured and propagated those cells into taste organoids, which are small 3D cell structures that are created outside of a living body to mimic what is happening inside.

Head shot of Josephine Egan, Senior Investigator at NIA.The team hypothesized that taste receptor cells were an ideal environment for asymptomatic infection of SARS-CoV-2. When people are unknowingly affected, it can be even more challenging to contain community spread of infection. Egan submitted a proposal focused on studying the interaction of SARS-CoV-2 and taste receptor cells to the Intramural Targeted Anti-COVID-19 (ITAC) funding program and ultimately was awarded support to move forward.

A key to this research is ACE2, which stands for angiotensin-converting enzyme 2. ACE2 is a protein that sits on the surface of some cells and is a known receptor for SARS-CoV-2, meaning the virus can attach to it, gain access to the cells, and make copies to spread the virus. Egan and her team have discovered that ACE2 is present on a subset of taste receptor cells. Therefore, it is possible for the virus’s spike protein to find a home within the taste buds in taste papillae. They also found that, in some cases, people who have recovered from COVID-19 have disrupted stem cell turnover in taste papillae, which could explain why some people have had ongoing taste changes even after the acute phase of COVID-19.

The goal now is to grow organoids of those stem cells to see if they contain ACE2, and then find out if the spike protein binds to them.

“If we can prove that is true, then we would have a model on which we could look for a whole host of things that might prevent or disrupt the ability of the spike protein to bind to ACE2 receptors in taste papillae,” Egan said. “That’s our goal and the one we will be working toward during the next year or two.”

Ultimately, this research could help discover methods to decrease the amount of the viral load in taste cells and lower the chance of transmission.

Progress even in challenging times

This science is taking place during a time when laboratory research looks much different than in the past. For example, before COVID-19, as many as 75 people might be working in the Baltimore-based NIA Clinical Research Center. Now, Egan and her team must schedule shifts to minimize the number of people at work so they can physically distance at six feet apart. They also must wear masks and disinfect work areas regularly. These safety protocols make some tasks, such as shared viewing of samples underneath a microscope, more difficult than it used to be.

“You miss the closeness of saying ‘look at this,’” Egan said. “Is this what I think it is? Can you look?”

Now Egan and her team must carefully leave their sample slides near the microscope after viewing and walk away before the next investigator can enter the area, disinfect it, and reload the slide to look at it. Then the safety measures begin again.

“This makes it difficult to keep the project on track because tasks take longer to complete,” Egan said, adding that especially if they are working in teams, physical distancing makes it difficult to connect around what is completed and what remains to be done.

Regardless, Egan and her team have been able to gain some insights, such as showing that ACE2 is expressed in a subset of taste receptor cells. Most important, they are still on track to meet their long-term goals.

Lessons learned

Still, looking back, Egan said she would not change much because her work is still moving forward despite COVID-19 challenges. However, she realizes that talking with more National Institutes of Health researchers beyond NIA, especially with those studying taste, would have helped increase her network of expertise. She finds networking more difficult to do virtually because, in her words, “I am a chatty, excitable type who has trouble connecting with people via Zoom.”

What if another pandemic was to occur? Egan has a few ideas of how things could run more smoothly. For example, she suggests adding a Clinical Laboratory Improvement Amendments (CLIA)-certified lab at the NIH Baltimore campus to enable on-site processing of diagnostic tests. She also suggests assembling a subcommittee of people who meet a few times a year and pre-emptively create scenarios of problems that could occur and ways to solve them.

Egan’s biggest lesson learned has been to question what she is doing and to not try to preserve a certain way of operating. COVID-19 has created a sense of urgency in everything she does, and she no longer hesitates on an idea or considers a different way of looking at things. Rather, if she thinks it will help her research, she will do it right then and there.

“No putting things off until the next day,” Egan said. “If it’s worth doing at all, you should do it now.”