Mapping the Future of Lyme Disease Research
By Mase Peterson
Brenda Rosario Perez never expected her personal experience with Lyme disease to become a professional calling. Diagnosed with Lyme disease over a decade ago, she now serves as the clinical research manager for the PROSSECO Study at Tufts University School of Medicine—one of the most ambitious investigations into the disease to date.
Originally from the Dominican Republic and raised in Providence, Rhode Island, Brenda brings a unique blend of lived experience, operational expertise, and research coordination to a complex, multi-site effort aimed at unraveling the mysteries of post-treatment Lyme disease syndrome. In this interview, she shares how her early exposure to developmental research, her evolving role across institutions, and her personal health journey have all led her to this groundbreaking work.
What’s your story? Tell us a bit about where you’re from, what brought you to Tufts, and how you got involved in the Lyme Disease Initiative.
I am originally from the Dominican Republic, and I came to the US (Providence, RI) when I was 12. I was fortunate enough to attend the College of the Holy Cross in Worcester, MA, where I took a course in physiological psychology with Professor Alo Basu. She first introduced me to research as a practice for exploring questions in a way that is impactful and meaningful for understanding health and development. After graduating in 2014, I joined the Brown Center for the Study of Children at Risk, examining developmental trajectories of very premature infants. It was around this same time that I was diagnosed with Lyme Disease, though I did not know much about it at the time.
Over the past decade, I’ve advanced through roles in data collection, coordination, data management, and operations management across various studies. Now, more than ten years after my Lyme diagnosis, I have the incredible opportunity to apply my professional skillset to better understand a disease that has had a personal impact on me.
How does managing the PROSSECO Study compare to your previous research roles?
The PROSSECO Study has, by far, the largest number of sites I have worked with; almost 20 sites across Massachusetts and Maine, and we plan for this number to keep growing. The infrastructure of the research team is therefore incredibly diffuse, especially as it includes not just study staff, but physicians and administrators at each of the sites.
At Tufts, I am currently working with 10 of these sites, which are all private practices, as opposed to hospital-affiliates. Private practices often need more flexible protocols that accommodate their leaner staffing models and different workflow patterns. Moreover, the PROSSECO study is incredibly novel, which is exciting, but also makes implementation more challenging, as there is less in the way of previous practice to draw on. The seasonality of Lyme disease also demands strategic and precise planning to be able to recruit while the iron is hot.
How are data analytics and technology shaping the way we understand and track Lyme disease through observational studies like PROSSECO?
The PROSSECO study is an incredibly important step forward in how we intend to use data analytics and technology to better understand Lyme disease. We’ve developed REDCap databases to standardize data collection across all sites in our geographically diverse research network. This approach helps minimize unintended biases that could arise if each site collected data independently.
We plan to use a multi-faceted approach to data collection and analysis that would not have been possible 10 years ago. Multiple data streams will relate to individuals' clinical observations, patient-reported outcomes, laboratory results, genetic data, and biospecimen characterizations, with data pipelines to transport the data. This approach will allow us to identify patterns and associations that likely would not be seen when looking at distinct data sources independently.
We will also apply machine learning algorithms and statistical modeling to create a probabilistic model of the experiential, host, and bacterial factors that contribute to post-treatment Lyme disease syndrome. Such models will allow us to visualize relationships between variables and potentially predict if certain patterns of genetic profiles, clinical signs, and symptoms in conjunction with environmental factors lead to certain post-treatment results in patients.
Moreover, we will employ high-throughput technologies (e.g., single cell RNA expression sequencing, proteomics array technologies, microbiome sequencing) that will produce enormous amounts of data, which will require advanced computational analysis. We hope to connect these high-throughput technologies in ways we have not yet imagined with our clinical data to create a model that can identify at-risk patients early, potentially inform treatment decisions based on patient profiles.
Ultimately, technological advancements will change our understanding of Lyme disease from predominantly observational to understanding the disease mechanistically, which we hope will lead to better diagnostic tools, better preventative strategies, and better therapies for patients with persistent symptoms.
What are some of the biggest challenges in coordinating multi-site research, and how do you ensure consistency and quality across different locations?
When working across sites, it is crucial to have an understanding of all of the ways that each site is different, whether it be in their facilities, their staffing, or especially in their institutional regulations. A protocol for any study must be constructed within the constraints of the institution, but with a study like PROSSECO, we have to find a way to build a protocol that can be implemented almost identically across all sites, considering all of the conflicting constraints of all the sites. Once this is developed, training becomes an equally daunting task. Every site has many people, all with different backgrounds, who will be involved in the research at some level. So, whether it is the step-by-step procedures for a specific visit, or the tools and technologies being used, every single person needs to be equally prepared.
Beyond understanding site differences, we've implemented several concrete quality assurance measures. We've developed standardized operating procedures with clear decision trees to accommodate site-specific variations while maintaining protocol integrity. Our electronic data capture system includes real-time validation checks to flag possible issues immediately. In addition, the lead coordinators meet regularly to go over procedures together to ensure they are consistent across sites. We have also created tailored workflows for each site so that we are all aware of exactly how those sites will complete the procedures while adhering to the protocol. These organizational efforts have created a harmonized approach despite the inherent variability across our research network.
Given your background in both operations and data management, how do you strike a balance between logistical coordination and meaningful data collection in Lyme disease research?
There are times when operational and data needs can be at odds with one another, as what would be scientifically ideal isn’t always feasible given the constraints of a study, especially when it comes to human participants. However, synergy between the two can be achieved through having a strong understanding of what the scientific aims of the research are, and why. Often, there is more than one way to achieve those aims, so the balance comes from understanding them enough to develop procedures that are feasible and still address the overall goals.
A practical example of this balance is our approach to biospecimen collection. While collecting multiple blood samples over time would provide ideal data for tracking immune responses, patient adherence would likely suffer. Instead, we've prioritized fewer, strategically timed collections that capture key immunological windows while maintaining participant engagement. Similarly, when faced with the unpredictability of tick exposures, we developed a rapid response system that can deploy study resources when we get a potential Lyme diagnosis, making sure we capture early-stage data without overwhelming our clinical sites.
What excites you most about the future of Lyme disease research—and how do you see your own work helping to push the field forward?
Despite the field of Lyme disease research greatly progressing in recent years, there is still a small but significant subset of people with Lyme disease that continue to experience symptoms long after standard antibiotic therapy. The reason for this is currently unknown. The PROSSECO study represents not just a first step, but a quantum leap in our approach by combining multi-site clinical data with molecular analyses. My contribution through operations management will help create the infrastructure that makes this comprehensive work possible. Such large-scale comprehensive work has significant implications for not only understanding disease presentation in this group, but for informing interventions to improve treatment and outcomes. The potential to identify early intervention points that could prevent chronic symptoms gives this work profound meaning for me and could transform the landscape of Lyme disease treatment.
Tufts is home to one of the world’s most comprehensive groups of tick-borne disease researchers, the Tufts Lyme Disease Initiative. Led by co-directors Linden Hu, the Paul and Elaine Chervinsky Professor of Immunology, and Robert P. Smith, a physician at Maine Medical Center and professor of medicine at Tufts, the team recently secured a $20.7 million federal grant, further solidifying Tufts’ position as a global leader in Lyme disease research.