A $13.3 million federal grant will support a Cornell-led research effort aimed at answering one of immunology’s most difficult questions: How immune cells communicate inside living tissue as inflammation, infection and healing unfold.
The five-year grant from the National Institutes of Health will fund a collaboration between Cornell University and the University of Rochester Medical Center. Researchers will use advanced imaging, spatial genomics and computational tools to study immune responses in far greater detail than traditional blood samples or biopsies allow.
The project could help shape future treatments for inflammatory diseases, autoimmune disorders and infections by giving researchers a clearer look at how immune cells behave in the places where immune responses actually happen.
Deborah Fowell, professor and chair of microbiology and immunology in Cornell’s College of Veterinary Medicine, will lead the program. She also directs the Cornell Center for Immunology.
Fowell said the research is focused on understanding immune responses inside tissues using tools that allow scientists to watch those responses in real time at inflamed sites.
Researchers will track immune cells in real time
Immune responses do not happen evenly across the body. They are highly localized, constantly changing and shaped by interactions between cells inside specific tissues.
That makes them difficult to study with conventional methods.
Blood samples can show what immune cells are circulating in the body, and biopsies can capture a snapshot of tissue at one moment. But those methods often miss the location, timing and movement of immune activity.
Cornell researchers want to close that gap.
The project will study how immune cells organize into specialized “niches” inside tissues. Those niches are where cells exchange signals that influence inflammation, infection response, tissue repair and immune memory.
To capture those interactions, researchers will use two- and three-photon intravital microscopy. The imaging technology, pioneered at Cornell, allows scientists to track immune-cell behavior deep inside living tissues, including lymph nodes, skin and lung tissue.
The imaging work will be paired with spatial transcriptomics, a technology that measures gene activity while preserving where cells are located inside tissue.
That combination gives researchers a more complete picture: what kind of immune cell is active, where it is located, what it is doing and how that activity changes over time.
Cornell, Rochester teams will combine expertise
The program brings together immunologists, engineers and computational scientists from Cornell and the University of Rochester Medical Center.
Research projects will be led in collaboration with Fowell by Mandy McGeachy and Brian Rudd in Cornell’s Department of Microbiology and Immunology, along with Minsoo Kim at the University of Rochester Medical Center.
Iwijn De Vlaminck, professor of biomedical engineering in Cornell’s Duffield College of Engineering, will direct the project’s Spatial Transcriptomics Core.
De Vlaminck said spatial transcriptomics allows researchers to measure cellular identity, immune receptor specificity and location at the same time. More traditional methods, including imaging or single-cell sequencing, typically capture only part of that picture.
The project will add a fourth dimension: time.
By moving between real-time imaging and molecular data, researchers expect to better understand the signals that drive and regulate immune function inside tissues.
Technology cores will support the work
The grant also supports two technology innovation hubs, or cores, that will provide advanced facilities and expertise across the program’s research projects.
The spatial transcriptomics core will be managed by De Vlaminck. A specialized imaging core will be directed by Chris Xu, professor of applied and engineering physics. Nozomi Nishimura, associate professor of biomedical engineering, and Chris Schaffer, professor of biomedical engineering, will serve as co-directors.
All three are part of Cornell Engineering.
Fowell said the cross-university and cross-disciplinary collaboration is essential because the project depends on tools developed by engineering researchers.
The work builds on prior research from the Fowell, Rudd and De Vlaminck laboratories. Earlier this year, the teams published findings in the Proceedings of the National Academy of Sciences showing how to connect spatial gene-expression data with immune-cell identity and function.
The newly renewed NIH funding will expand that work.
Grant renewed for third funding period
The grant was first awarded to Fowell in 2014 while she was at the University of Rochester. It has now been renewed for a third five-year funding period.
Since joining Cornell in 2020, Fowell has expanded the program to include new investigators from microbiology and immunology, biomedical engineering and applied and engineering physics.
The NIH funding also includes support for seed grants to develop next-generation tools for studying immune responses. A biennial Immune Imaging Symposium will bring researchers from around the world to Cornell.
Those efforts will be supported by Cornell’s College of Veterinary Medicine and Duffield College of Engineering.
Gary Koretzky, Cornell’s vice provost for research, said the project reflects the value of collaboration across fields, bringing together immunology, engineering and computational biology to pursue discoveries that would be difficult within a single discipline.
For Cornell, the grant places Ithaca at the center of a major research effort that could change how scientists understand immune behavior inside the body — and eventually how doctors treat diseases driven by inflammation and immune dysfunction.
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