How the Celiac Disease Foundation is investing in the next generation of discovery
Understanding celiac disease requires understanding the human immune system and that has long been one of the field’s biggest challenges. For decades, researchers have relied on mouse models to study autoimmune and inflammatory diseases. While these models have been invaluable, they come with an important limitation: many immune cells behave very differently in mice than they do in humans. Those differences matter, especially in a disease like celiac disease, where subtle immune interactions drive intestinal damage.
That’s where the work of Dr. Esen Sefik, a Celiac Disease Foundation–funded investigator and Assistant Professor at Yale University, represents a major step forward. With support from the Celiac Disease Foundation–Takeda Early Career Research Award, Dr. Sefik developed a new humanized mouse model that more accurately mirrors the human immune system, addressing a long-standing gap in celiac disease research.
Celiac disease is caused by an inappropriate immune response to gluten, leading to chronic inflammation and damage to the small intestine. While gluten-specific T cells are central to this process, researchers increasingly recognize that innate immune cells, particularly neutrophils, also play an important role in inflammation and tissue injury.
The problem is that most existing humanized mouse models do not generate functional human neutrophils. Without them, researchers have been unable to fully model the immune environment that exists in people with celiac disease.
“Neutrophils are the most abundant immune cells in the human bloodstream, but they’ve been largely absent from humanized mouse models,” said Dr. Sefik. “That has limited our ability to study how early immune responses unfold in human inflammatory diseases like celiac disease.”
In a study published in Proceedings of the National Academy of Sciences (PNAS), Dr. Sefik and colleagues described a new humanized mouse model called MaGIC, designed to support robust development of human immune cells including fully functional human neutrophils.
In this model, human neutrophils are not only present but behave as they do in people. They migrate to sites of inflammation, engulf pathogens and debris, produce reactive oxygen species, and form neutrophil extracellular traps. These are core immune functions that had previously been impossible to study in living systems.
“This model allows us to observe human immune cells functioning in real tissue environments, rather than relying solely on in vitro systems,” Dr. Sefik explained. “That’s essential for understanding complex diseases like celiac disease, where multiple immune cell types interact over time.”
The MaGIC model also supports human monocytes, macrophages, and other immune cells that contribute to intestinal inflammation. Together, these features create a more complete and physiologically relevant immune system than prior models could achieve.
Beyond building a better model, Dr. Sefik’s work integrates cutting-edge technologiesincluding single-cell RNA sequencing, spatial transcriptomics, and analysis of human intestinal biopsies to directly compare immune responses in patients with those observedin the laboratory.
This approach allows researchers to ask questions that were previously out of reach: How does the immune response change at disease onset? Which immune cells drive tissue damage? And which pathways might be targeted to interrupt the disease process before long-term injury occurs?
“Our goal is to understand the earliest immune events that lead to celiac disease,” said Dr. Sefik. “By aligning patient data with humanized models, we can begin to test mechanisms in a way that is both rigorous and clinically relevant.”
This kind of innovation depends on early support. The CDF–Takeda Early Career Research Award is designed to help promising investigators establish independent research programs focused on celiac disease at a pivotal stage in their careers. For Dr. Sefik, that support enabled the development of a novel research platform, publication in a leading scientific journal, and generation of data that strengthened subsequent federal grant applications.
“Early-career funding is one of the most powerful investments we can make,” said Marilyn Geller, CEO of the Celiac Disease Foundation. “It allows talented scientists to pursue bold ideas that may not yet be ready for large federal grants, but that have the potential to transform the field. When we support researchers like Dr. Sefik, we’re not just funding a single project. We’re investing in the future of celiac disease research and the pipeline of discoveries that patients are counting on.”
Progress like this is only possible when innovative science is met with early support. By funding researchers at pivotal moments in their careers, the Celiac Disease Foundation helps turn promising ideas into discoveries that can change lives. Your gift helps fuel the next breakthrough in celiac disease research. Give today to support research like this at: https://celiac.org/researchawards/support/