AWIS member Dr. Monica Embers

Portrait of Persistence: Dr. Monica Embers

04/21/2023
By Elaine Nkwocha, PhD Student

Would it surprise you to learn that there are more Lyme disease cases than all HIV and breast cancer cases combined? I learned this from an enlightening 2022 documentary called The Quiet Epidemic. It focuses on a young girl from Brooklyn and a Duke University scientist who both developed chronic Lyme disease and then set out to prove their medical condition is real.

While 80% of those who contract Lyme disease recover after receiving a course of antibiotics, two million others suffer debilitating long-term effects. Medical professionals have yet to figure out how to help these patients. Some doctors don’t even acknowledge that there is a problem, and too few researchers have chosen to study the long-term effects of the disease.

However, Dr. Monica Embers, Associate Professor and Director of Vector-Borne Disease Research at the Tulane National Primate Research Center (TNPRC), has made this the focus of her career. “I can’t tell you how many people told me, ‘Do not do this. This is not a good research question for you to answer.’ But fortunately, I didn’t listen. I thought it was an important research question that needed to be answered,” said Dr. Embers. “It became obvious to me that a lot of people who are treated with the standard Lyme disease course remain ill. I want to figure out how to make the prognosis better for them.”

Dr. Monica Embers
Monica Embers, PhD, associate professor of microbiology and immunology at the Tulane National Primate Research Center. Photo courtesy of Paula Burch-Celentano, Tulane University.

The Question of Persistence

Dr. Embers became intrigued by how pathogens can evade hosts’ immune responses and persist while she was a doctoral student at Penn State. “Lyme was becoming more prevalent in Pennsylvania. When I learned that Borrelia burgdorferi are capable of evading host immunity, and of even suppressing the immune responses to ensure persistence, it became very interesting to me,” said Dr. Embers. “I contacted Dr. Mario Philipp, who was a faculty member at Tulane. He developed the nonhuman primate model for studying Lyme disease. I asked if he had any postdoctoral positions available. One thing led to another, and I’ve been here ever since.”

When Dr. Embers joined TNPRC, she began zeroing in on immune evasion. She posited that the standard, 28-day course of doxycycline may not work, because of the bacteria’s ability to conceal itself and enter a slow-growing, dormant phenotype. “The corkscrew shape of Lyme spirochetes allows them to burrow into joints, tissues, or organs like the brain or the heart,” she explained. “The spirochetes are very hard to find. They are not in the bloodstream. You might be able to pick up antigens in the urine, but they are sporadic.” Having access to large animal models and to translational research opportunities at Tulane, she pursued the question of persistence in the face of antibiotic treatment.

Dr. Embers and her team used a research process called xenodiagnosis to recover lingering spirochetes from infected and antibiotic-treated macaques. In this study, the team fed Borrelia burgdorferi-containing ticks on the primates, permitting infection. The team then treated the primates for 28 days with doxycycline and then placed uninfected ticks on the animals. When these new ticks fed, they acquired Borrelia burgdorferi, proving that the infection persisted after antibiotic treatment.

Other researchers have questioned this conclusion, arguing that the spirochetes are not alive and functional because you can’t culture them. Dr. Embers and her team are working to publish research showing that you can culture them and that they are transcriptionally active.

Going Against the Grain

Studying and treating Lyme disease are complicated endeavors because the bacteria are so hard to find. It’s hard to prove that someone has a chronic, persistent infection. It’s hard to detect, even with an antibody test. “How do you have a reliable antibody test when the bacteria can suppress the immune response?” Dr. Embers asked. “I’ve seen several of my nonhuman primates that I can prove are chronically infected, and I can’t find antibodies.” This dilemma underlines the importance of a reliable diagnostic test.

It also explains why chronic Lyme disease has become so controversial. Doctors struggle to diagnose and determine that someone has a persistent infection. No matter what she publishes, it gets discounted. She asserted, “We value the integrity of our research very much. We have the proper controls and do the science the right way. In some cases, we send our samples to another lab and have them validate them without knowing what the samples are.”

illustration of ticks carrying lime diseaseCritics have countered that although Dr. Embers has found spirochetes that persist in nonhuman primates, she has not provided proof that this happens in humans. So now her team is looking for this evidence in human autopsy specimens. “My team is finding persistent spirochetes in humans who were diagnosed with Lyme disease and, in some cases, treated extensively with antibiotics, and the spirochetes are still there,” Dr. Embers shared. “There is no doubt in my mind that this is a chronic, persistent infection that requires a new treatment model for all patients, especially for those in the chronic phase.”

One of the most poignant parts of The Quiet Epidemic centers on Julia, the young girl in Brooklyn. Her doctors kept insisting that she was depressed, refusing to believe that she was suffering from Lyme disease. When scans revealed damage to parts of her brain that control her ability to walk, she finally had proof that her symptoms had a physical cause. Such evidence is needed for critics to believe that chronic Lyme disease exists, and that further research and treatment regimens are crucial to relieve the symptoms experienced by those who suffer from it. “The guidelines for Lyme disease treatment have been in place for a long time without accounting for the new research,” Dr. Embers asserted.

The Tulane team has shifted their focus to identifying different treatment regimens, diagnostics, and prevention. “We need to find a treatment regimen that does cure the infection. We need to arm the clinicians with what they need to cure their patients.”

Innovations on the Horizon

The film also featured Dr. Neil Spector, a renowned physician-scientist and cancer researcher at Duke University who contracted Lyme disease. He experienced serious heart damage due to the persistent bacteria and received a transplant in 2009. During his battle, he began applying his knowledge of precision oncology to target Borrelia burgdorferi and to Bartonella, a common bacterial Lyme disease coinfection, instead of using a broadspectrum antibiotic. Unfortunately, he died in 2020, but Dr. Embers and other researchers continue to follow up on his groundbreaking ideas.

The patients that are the sickest often have this coinfection of Borrelia burgdorferi and Bartonella because they are immunosuppressed. Dr. Embers’ team has been working with Dr. Timothy Haystead, one of Dr. Spector’s Duke University colleagues, and with Dr. Ed Breitschwerdt at North Carolina State University to test novel small-module therapies that target Borrelia burgdorferi and Bartonella together.illustration of lime disease symptoms

They want to cure every patient at all phases of infection. “If you think about tuberculosis, multiple antibiotics are administered because it is a dormant, persistent bacterial infection,” Dr. Embers explained. “Lyme disease can also be a dormant, persistent bacterial infection that requires multiple antibiotics to eradicate it.”

The Tulane team is also working to develop live-imaging diagnostics. Dr. Embers said, “If you have a chronic urinary tract infection, you culture the bacteria from the urine. With Lyme disease, you can’t do that.” The only option available now is to look very deeply into the tissues of necropsy specimens to find the spirochetes. “Imagine if we could identify the bacteria in those patients suffering chronic symptoms associated with Lyme disease by using radioactive tags that bind specifically to the borrelia,” Dr. Embers speculates, “then we could use a PET CT to diagnose the patient.”

In addition, scientists are making progress on the vaccine front. Valneva and Pfizer recently went into an equity subscription agreement to develop a Lyme disease vaccine candidate, VLA15, which is currently in clinical trials and testing in humans, with a planned market release in 2025.

Since ticks can transmit a lot of other things, not just Lyme, another research effort is underway to create an anti-tick vaccine that would prevent the arachnids from feeding on us. According to Dr. Embers, animal studies show that repeated tick biting can induce immune responses that reduce the tick’s ability to feed and to transmit pathogens. Her team is collaborating with people on several different preventative research programs for tick-borne diseases.

If There Is a Will, There Is a Way

It was a little scary for Dr. Embers to investigate bacterial persistence. Now she is less worried about tackling controversial research areas. She is more inclined to conduct research that will have a real impact, rather than to pursue projects that easily attract funding or to chase after questions that are easier to answer. She prefers going with her gut and her heart.

“I’ve learned a lot about resilience through my work and my life,” Dr. Embers asserted. ““When my condo flooded during Hurricane Katrina, instead of dwelling on the damage, I focused on how to make the condo look good again. With the insurance money, I was able to put in the flooring I wanted and paint the walls the color I wanted. There can be beauty on the other side of hardship. If you believe in yourself and the process, you can get there.”

AWIS member Elaine NkwochaElaine Nkwocha is a Doctoral Student in the Department of Biological Sciences at Louisiana State University. Her research focuses on determining the mechanisms by which a biofilm regulator protein (BifR) regulates bacterial physiology and fitness. She sits on the Board of the Women’s Council of Greater Baton Rouge, Louisiana State. She is a changemaker, an education advocate, and an emerging global leader. She is passionate about helping young people tap into and live out their passion and potential through teaching and mentorship. She is interested in teaching and learning, student success, science education, and educational leadership. She founded two organizations; one (Brave Space with Elaine) provides academic mentorship, and the other (Elaine Education Foundation) helps children to access education. 

This article was originally published in AWIS Magazine. Join AWIS to access the full issue of AWIS Magazine and more member benefits.