Investigating How Neutrophils Fight Back: My MBR Research Experience at Tufts GSBS

As part of a Tufts GSBS research spotlight series, recent MBR graduates discuss their thesis projects, key findings, and the skills they developed through independent, PhD‑level research training.

By Maisie Lake, MBR26

Member of: The Joan Mecsas Lab

During my time in the Master of Biomedical Research (MBR) program at Tufts Graduate School of Biomedical Sciences, I had the opportunity to complete an independent thesis project focused on understanding how immune cells respond to bacterial infection. My research examined the host-pathogen interaction between Yersinia pseudotuberculosis (Yptb) and neutrophils, which is one of the body’s first lines of defense against invading microbes.

Understanding the Battle Between Bacteria and the Immune System

Neutrophils play a critical role in protecting the body from infection. They deploy a range of antimicrobial strategies, including producing reactive oxygen species (ROS), adhering to infected tissues, and engulfing pathogens through phagocytosis. However, some bacteria have evolved sophisticated mechanisms to evade these defenses.

Yersinia pseudotuberculosis is one such pathogen. It uses a molecular syringe known as the type III secretion system (T3SS) to inject effector proteins, called Yops, directly into host immune cells. These Yops interfere with normal neutrophil function, allowing the bacteria to survive and spread. By studying how neutrophils are altered during infection with Yptb, researchers can identify key host proteins that are essential for mounting an effective immune response.

My Research Focus and Approach

The goal of my project was to determine whether the function of two tyrosine kinases, Bruton’s tyrosine kinase (Btk) and proline-rich tyrosine kinase 2 (Pyk2), which are required for neutrophil ROS production and phagocytosis. Specifically, I wanted to understand how these proteins function following integrin activation or during infection with Yptb.

To do this, I used Btk knockout (KO) and Pyk2 knockout (KO) cells derived from a parental cell line, CG12, an immortalized ER-HoxB8 myeloid progenitor cell line. These progenitor cells can be differentiated into neutrophils, making them a powerful and flexible model system. Using these cells, I conducted assays to measure ROS production following integrin stimulation with polyRGD, as well as phagocytosis after infection with Yptb mutants lacking the T3SS.

Growing as an Independent Researcher

I conducted this project independently, with guidance from other students in the lab and my advisor, Dr. Joan Mecsas. This experience was incredibly formative. Early on, one of my biggest challenges was knowing how to move forward after obtaining results—what questions to ask next and how to design experiments to answer them.

Through this project, I learned how to troubleshoot complex neutrophil functional assays, critically analyze data, and think strategically about experimental design. Over time, I became much more confident in my ability to ask meaningful scientific questions and plan clear, focused experiments to address them. This growth in scientific independence is one of the most valuable skills I gained from the MBR program.

Key Findings and Why They Matter

One of the most important findings from my research was identifying a critical role for Btk in ROS production and adhesion following integrin activation. Interestingly, Btk’s role in integrin-mediated ROS production was dependent on its kinase activity, while its role in adhesion was kinase-independent. This was surprising and suggests that Btk may function as a scaffold protein during adhesion, with domains beyond its kinase domain playing a key role.

In addition, I found that Pyk2 is essential for the phagocytic uptake of Yptb. Together, these findings help clarify how distinct signaling pathways regulate different neutrophil functions, including ROS production, adhesion, and phagocytosis.

Understanding these mechanisms is important because it provides insight into how immune cells coordinate their responses during infection—and how pathogens disrupt those responses. This knowledge can ultimately inform future research into immune signaling and host defense.

How the MBR Program Shaped My Experience

The MBR program at Tufts GSBS played a central role in preparing me for this research experience. The program emphasized independent thinking and hands-on experimentation, which allowed me to take ownership of my project from start to finish. Taking PhD-level graduate courses also helped me work through complex questions that arose during my research and strengthened my ability to engage with the scientific literature.

Mentorship was another highlight of my experience. Dr. Joan Mecsas was an incredibly supportive advisor who consistently challenged me to think more deeply, communicate more clearly, and push myself as a researcher and writer. That mentorship made a lasting impact on my development as a scientist.

Looking Ahead

After graduating from the MBR program in May 2026, I will be continuing my training in biomedical research as a PhD student at the University of Maryland. Completing an independent thesis project gave me confidence in my scientific abilities and confirmed that pursuing a PhD is the right next step.

I am deeply grateful for the MBR program and the opportunities it provided. This experience helped me grow not only as a researcher, but also as a writer, thinker, and presenter. I leave Tufts GSBS feeling prepared, motivated, and excited for what comes next.

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