Spatial Immunology Unit
Established in 2023
Major Areas of Research
- Mycobacterium tuberculosis infection
- Granuloma formation and function
- Immune cell interactions and tissue organization
Program Description
Our unit studies how immune cells are organized and programmed within tissues during chronic inflammation, with a primary focus on tuberculosis (TB) and granuloma biology. TB granulomas are highly structured immune environments that simultaneously contain infection and enable bacterial persistence. Our work seeks to understand the cellular interactions and microenvironmental cues that govern these opposing outcomes. To do this, we integrate cutting-edge spatial mapping and multiplexed imaging approaches to resolve tissue architecture at single-cell resolution. These technologies allow us to define where specific immune and stromal populations reside, how they interact, and how their functional states are shaped by the local environment. We are particularly interested in how spatial context influences immune cell behavior in ways that cannot be captured by dissociated or bulk analyses. Complementing our work in human tissues, we develop and apply human-based organoid systems that model key features of granuloma formation and immune activation in vitro. These platforms enable controlled perturbation of host and pathogen factors, allowing us to dissect mechanisms of immune organization and function with high precision. A central theme of our research is immunometabolism. We seek to understand how metabolic constraints and adaptations within the granuloma microenvironment influence immune cell function and fate. We investigate how nutrient availability, hypoxia, and metabolic signaling pathways shape immune responses and contribute to either pathogen control or disease progression. Ultimately, our goal is to translate these insights into host-directed therapeutic strategies for TB and other granulomatous diseases. By identifying the principles that govern effective versus dysfunctional immune organization, we aim to inform new approaches that reprogram tissue immunity to improve disease outcomes.
Biography
Education
B.S., Microbiology, 2016, University of Maryland, College Park, Maryland
Ph.D., Immunology, 2022, Stanford University, California
Erin McCaffrey began her academic training at the University of Maryland, College Park, where she earned a B.S. in Microbiology in 2016. During this time, she conducted research with Dr. Rohan Fernandes at the Children’s National Medical Center Sheikh Zayed Institute, developing a tumor-targeting biohybrid system composed of Prussian Blue nanoparticles and attenuated Salmonella typhimurium. She went on to pursue her Ph.D. in Immunology at Stanford University as an NSF Graduate Research Fellow, specializing in Computational and Systems Immunology. Working under Dr. Michael Angelo, she leveraged highly multiplexed tissue imaging technologies to generate the first spatial single-cell atlas of human tuberculosis (TB) granulomas. Her work identified an immunosuppressive niche within granulomas that parallels the tumor immune microenvironment. In addition, she developed novel computational frameworks for analyzing the spatial organization of immune responses across diverse contexts, including tuberculosis, HIV, cancer, pulmonary inflammation, and neurodegeneration. Erin then completed a post-doctoral fellowship with Dr. Mark Davis at Stanford University and a visiting fellowship with Dr. Damein Portevin at the Swiss Tropical & Public Health Institute where she extended her work in TB with in vitro organoid models of lymphoid follicles and granuloma formation. As an Independent Research Scholar, she integrates spatial mapping technologies with human in vitro organoid systems to define the principles governing immune cell programming and tissue organization in tuberculosis and other forms of granulomatous inflammation.
Selected Publications
McCaffrey EF, Delmastro AC, Fitzhugh I, et al. The immunometabolic topography of cellular organization and bacterial control in tuberculosis granulomas. Nat Immunol. 2026;27(4):867-880. doi:10.1038/s41590-026-02431-8
Zheng Y, Jean Pierre M, Ansaldo E, et al. Alternatively activated monocyte-derived myeloid cells promote extracellular pathogen persistence in pulmonary fungal granulomas. J Exp Med. 2026;223(5):e20260208. doi:10.1084/jem.20260208
Schrom EC, McCaffrey EF, Sreejithkumar V, et al. Spatial Patterning Analysis of Cellular Ensembles (SPACE) finds complex spatial organization at the cell and tissue levels. Proc Natl Acad Sci U S A. 2025;122(6):e2412146122. doi:10.1073/pnas.2412146122
McCaffrey EF, Donato M, Keren L, et al. The immunoregulatory landscape of human tuberculosis granulomas. Nat Immunol. 2022;23(2):318-329. doi:10.1038/s41590-021-01121-x
Research Group
The Spatial Immunology Unit integrates spatial mapping technologies and human-based in vitro organoid models to define the principles of immune cell programming and organization during tuberculosis and other forms of granulomatous inflammation.
