Alexandra Bayer Wildberger, PhD, a postdoctoral associate in the lab of Kevin O’Connor, PhD, was selected to receive a 2026 American Brain Foundation Next Generation Research Grant in the area of myasthenia gravis for her project, “Investigating the Role of the Immune System’s First Responders in Myasthenia Gravis.”
Learn more about Bayer Wildberger’s work and how this grant supports both future professional plans and advances in myasthenia gravis research.
My research focuses on autoimmune neurological diseases, especially myasthenia gravis, with a particular interest in understanding why the same disease can look so different from one patient to another. I’m especially interested in the antibodies that drive disease and how distinct immune profiles may influence symptoms, severity, and response to treatment.
What motivates me is the idea that if we can better understand these mechanisms, we may be able to move toward more precise and individualized care. Myasthenia gravis is a highly heterogeneous disease, but that heterogeneity is also informative, and it likely reflects underlying biology that we don’t yet fully understand. I see our work as an effort to uncover those mechanisms and translate them into better ways to classify and ultimately treat patients.
I am a senior postdoctoral fellow in the lab of Kevin O’Connor, PhD, where I work on translational immunology projects aimed at understanding the mechanisms driving autoimmune disease and identifying potential therapeutic strategies. My work focuses on autoantibodies, adaptive immune responses, and disease pathogenesis across different clinical contexts.
A major focus of my work is myasthenia gravis. I study patient-derived autoantibodies and the immune mechanisms behind their pathogenic effects, with the goal of understanding how they contribute to disease and how they might be targeted therapeutically. For the project recently, I’ve also been involved in exploring less-studied IgM autoantibodies, which appear to play a role in a subset of patients.
This grant is very meaningful to me because it supports a line of work that has developed gradually over several years of training and research. Myasthenia gravis has been central to my scientific path since my early graduate training and has remained a consistent focus throughout my work at Yale.
Importantly, the project supported by this award builds directly on recent data we generated, suggesting that less-studied IgM autoantibodies may contribute to disease in a subset of patients. While most research and current therapeutic approaches have focused on IgG, our findings raise the possibility that IgM may also play a role in disease mechanisms in certain cases.
With this support, I will be able to further investigate this overlooked component of the immune response by building a collection of patient-derived IgM autoantibodies and characterizing them at both the molecular and functional levels. Ultimately, this work aims to clarify whether and how IgM contributes to disease, and whether incorporating this information could help move us toward more precise and individualized approaches to diagnosis and treatment.
Our hypothesis was that IgM autoantibodies may contribute to disease in a subset of patients with myasthenia gravis, even though most research and current therapeutic approaches have focused on IgG. We wanted to explore whether this underappreciated arm of the immune response could help explain some of the clinical and biological heterogeneity seen in the disease.
In our recent work published in PNAS, we used an IgG-specific protease to remove the Fc portion of IgG antibodies from serum samples of patients with myasthenia gravis. We then measured complement activation, a key mechanism of tissue injury in the disease. As expected, disarming IgG strongly reduced complement activation. However, in a subset of patient samples, complement activity did not fully disappear after IgG was cleaved, suggesting that another immune factor was contributing to the response. Importantly, when we used an IgM-specific protease, we were able to suppress these remaining effects. This suggested that IgM autoantibodies were not simply present in the background, but could be functionally relevant in driving disease mechanisms in a subset of patients.
From a clinical perspective, this matters because patients with myasthenia gravis do not respond uniformly to treatment. If different antibody classes contribute to disease in different patients, understanding those differences could eventually help guide more targeted therapeutic strategies. While this is still an early step, the broader goal is to move toward a framework where treatment decisions are informed not only by diagnosis, but by the underlying immune mechanisms driving disease in each individual patient.
My long-term goal is to become an independent investigator in autoimmune neurology, establish my own lab, and translate immunological insights into better treatments for patients. I also hope to create opportunities for the next generation of scientists, as my mentors have done – and continue to do – for me, by fostering rigorous, collaborative, and meaningful research grounded in patient impact.
This grant represents an important step in that trajectory. It gives me the opportunity to keep growing in the field of myasthenia gravis, to benefit from Yale’s exceptional academic and collaborative environment, and to further develop the skills and independence I need for the next stage of my career.
I am very grateful to Dr. O’Connor for his mentorship and support, and to everyone in the O’Connor Lab for creating such a collaborative and thoughtful environment. I am also sincerely thankful to Yale, as well as to the American Academy of Neurology, the American Brain Foundation, and the Myasthenia Gravis Foundation of America for funding this award and making this next step possible.