Research
The innate immune response plays a critical role in maintaining tissue homeostasis but can also contribute to the progression of diverse diseases (e.g. chronic infections, cancer, cardiovascular disease, autoimmune disease, fibrosis). Modulating innate immune cell function is a promising strategy for treating these diseases but we must first understand how innate immune cells integrate the diverse signals in the inflammatory environment into a specific and directed response, and how this is dysregulated in disease. Our work focuses on understanding how multicellular interactions, interactions with the complex tissue matrix, and soluble signaling contributes to innate immune regulation. Our group works at the intersection of engineering and immunology, using our knowledge of design principles and immune cell biology to investigate these fundamental questions in innate immunity. We design biomimetic microfluidic models inspired by in vivo biology to investigate human immune cell behavior in a physiologically relevant environment (Richardson, Calo, and Hind, 2021). This work is carried out with the goal of discovering new targets to control immune cell recruitment, resolution, and function.
Multicellular Interactions in Modulating the Innate Immune Response
Neutrophils, the most abundant innate immune cell type, play a critical role in clearing infections, healing wounds, and repairing damaged tissues. Unfortunately, dysregulation of neutrophil function contributes to chronic infections, cancer, cardiovascular disease, and autoimmune diseases. The neutrophil response is influenced by interactions with other cell populations but how these interactions regulate neutrophil function is not well characterized. We are using a variety of engineered platforms including our inflammation-on-a-chip device to investigate these interactions. Our group has shown that signaling from the vasculature, specifically endothelial cells, is critical in driving the innate immune response to infection (Hind, Blood, 2018). This is an important finding as both neutrophils and macrophages play an important role in vascular disease (Ignes-Romeu, 2025). We are now investigating the roles of other innate immune and immune responsive cells in regulating neutrophil function. Our early studies have indicated that macrophages play an important role in neutrophil regulation (Ignes-Romeu et al, 2024) and we are investigating this further. Additionally, we have discovered a novel regulatory mechanism for myeloid derived suppressor cells, a heterogenous immunosuppressive cell population, in diminishing the neutrophil response to infection (Weppner et al, 2025).
Varied Inflammatory Stimuli Differentially Regulate the Innate Immune Response
Neutrophils and other innate immune cells respond to diverse inflammatory events by integrating a myriad of proinflammatory cues including secreted cytokines, growth factors, lipid mediators, and, in the case of infection, pathogen-derived signals. The combination of signals present in an inflammatory environment can vary greatly and altered secretion of regulatory signals is known to be associated with dysregulated neutrophil function, particularly in the context of disease. Our lab has investigated the contributions of diverse pathogens and critical cytokines in regulating the neutrophil response. Specifically, we have found that clinically relevant, priority pathogens including Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella enterica, and Listeria monocytogenes, elicit diverse neutrophil responses and inflamed endothelial profiles (Richardson et al, 2023). Furthermore, we have recently discovered that the concentration of IL-6, an essential cytokine in the response to infection, regulates neutrophil and endothelial cell function in a concentration and pathogen-dependent manner (Owens et al, 2026).
Physical Environment in Modulating the Innate Immune Response
Diseases worsened by neutrophil dysregulation often have significant changes to the extracellular matrix including altered protein composition, crosslinking, and physical properties including modulus and viscoelasticity; yet the role of the extracellular matrix in regulating neutrophil function in unclear (Calo et al, 2025, review). We propose that the extracellular matrix is a crucial and underappreciated regulator of neutrophil function. To investigate this understudied mechanism of immune regulation we have investigated the role of collagen on the neutrophil response and found that both the collagen concentration (Calo et al 2024) and crosslinking (Calo et al 2026) has a significant effect on neutrophil extravasation and migration. We are now expanding our investigations into the roles of other extracellular matrix proteins and investigating both elastic and viscoelastic matrices.