Decoding Chronic Lyme: Investigating Epigenetic Signatures

By Mase Peterson

In the fight against Lyme disease, cutting-edge research is essential for advancing treatment and prevention strategies. Tanja Petnicki-Ocwieja, PhD, a research assistant professor at Tufts University School of Medicine, is a key contributor to this effort through her work with the Tufts Lyme Disease Initiative. This collaborative group of faculty, staff, and students is dedicated to eliminating the public health threat of Lyme disease by 2030.

Tufts is home to one of the world’s most comprehensive groups of tick-borne disease researchers. Led by co-directors Linden Hu, Paul and Elaine Chervinsky Professor of Immunology, and Robert P. Smith, a physician at Maine Medical Center and professor of medicine, the team recently secured a $20.7 million federal grant, further solidifying Tufts’ position as a global leader in Lyme disease research.

In this Q&A, part of a feature series spotlighting members of the Initiative, Professor Petnicki-Ocwieja discusses her research on the immunological and epigenetic mechanisms underlying chronic Lyme disease and its potential to transform patient outcomes.

Tell us a little about your background and what brought you to TUSM.

“I received a Bachelor of Science from the University of Illinois-Chicago and a PhD in microbiology from the University of Nebraska-Lincoln. My doctoral work focused on the identification of virulence factors in pathogenic bacteria and methods used to evade host immunity. To better understand host immune responses, I joined an innate immunity group at the Dana-Farber Cancer Institute/Harvard Medical School for post-doctoral training. There, I spent three years investigating microbial activation of innate immune pathways that contribute to chronic inflammation in the gut. I became interested in the immunological shifts in response to specific bacterial stimuli, which was difficult to address in conditions such as inflammatory bowel disease (IBD) that had polymicrobial and human genetic components. I joined Tufts and Dr. Linden Hu’s lab with the purpose of studying Lyme disease. Tufts has historically had a strong Lyme research program, being home to several renowned Lyme investigators, such as Dr. Hu. This tradition continues with the outstanding faculty assembled in the Lyme Disease Initiative, making TUSM one of the leading institutions in the field.”

What is your role in the initiative and is your team focusing on any specific aspects of Lyme disease research?

“The Program Project grant is a large-scale prospective study designed to characterize clinical, microbiological, and immunological aspects of patients with long-Lyme symptoms or post-treatment Lyme disease syndrome (PTLDS). I am one of the team members that will investigate immunological signatures that may distinguish PTLDS from Lyme-recovered patients. My primary interests are epigenetic modifications that are part of the innate immune memory response to repeated microbial exposure. Studies of epigenetic reprogramming have received renewed interest after the COVID pandemic, with researchers aiming to explain why patients with COVID had such distinct responses to the same virus and why some developed “long COVID.” We are similarly interested in why some patients with Lyme develop long-term symptoms and have shown that Lyme disease-causing bacterium induces innate immune memory. Our epigenetic studies have received funding from the Global Lyme Alliance, and with this Project Grant we hope to expand our understanding of Lyme-induced memory.”

What do you hope this research will achieve for patients with chronic Lyme Disease and the medical community?

“As part of the Program Project, we hope to identify epigenetic signatures and pathways that could be risk factors for PTLDS. In addition, our studies could provide insights into and reveal mechanistic commonalities with other post-infectious disease syndromes with similar symptoms, such as long-COVID.”

What challenges do you foresee and how are you addressing them?

“On my end, working with small sample sizes will likely be the biggest technical challenge. We will take advantage of sensitive next-generation sequencing and screening approaches to overcome those difficulties. In the future, we would be interested in comparing PTLDS immune signatures with other post-infectious disease or autoimmune patients, such as long-COVID, rheumatoid arthritis, or multiple sclerosis.”