Antimicrobial-resistance is a growing global health concern with deaths from antimicrobial-resistant infections predicted to outnumber cancer deaths by the year 2050. Our group postulates that harnessing the body’s natural response to pathogen invasion by controlling innate immune cell function could be an effective way to combat infection. However, to precisely control cell function, we first need a better understanding of the signals that drive the innate immune response to infection. Our group works at the intersection of engineering and immunology, using our knowledge of design principles and immune cell biology to investigate the innate immune response to infection. We design biomimetic microfluidic models inspired by in vivo biology to investigate human immune cell behavior in a physiologically relevant environment. This work is carried out with the goal of discovering new targets to control immune cell recruitment, resolution, and anti-microbial function.
Multicellular Interactions in Modulating the Immune Response
The innate immune response is a complicated process that involves a coordinated effort by many cell populations; however, the role of these multicellular interactions in driving immune cell function is unclear. Currently, immune cell function is studied in one of two ways: using in vitro devices in which a single cell type’s function is studied in response to an activating signal or using an in vivo model whose inherent complexity makes it difficult to tease apart the role of specific cellular interactions on immune cell function. Therefore, a need exists for in vitro devices that recapitulate important aspects of the infectious microenvironment to study immune cell function. Our group is designing new biologically inspired in vitro models that incorporate multicellular interactions and physiologically relevant structures to recapitulate the infectious microenvironment. We are then using these models to investigate the role of cell-cell interactions on immune cell migration and antimicrobial function in response to a variety of infections.
Physical Environment in Modulating the Immune Response
In addition to cell-cell signaling, the physical environment can have a significant impact on the ability of immune cells to reach and fight an infection. Tissue properties such as stiffness, density, and ligand presentation can alter the polarization and functionality of many different cell types. Additionally, these changes in cell phenotype could alter their interactions with each other. Our group is investigating how characteristics of the physical environment alter immune cell migration and multicellular interactions during an infection.
Non-Traditional Immune Cell Migration and Function
New subsets of immune cells, such as Myeloid Derived Suppressor Cells, have been identified using single cell genomic techniques. These cells are most prevalent in cancer patients, but they can also have an important role in infection. Little is known about how these cells migrate to a site of infection, become activated by invading pathogens, or interact with other cells of the immune system. Our group is investigating the modes in which these immune cell subsets migrate and how they function in an infectious environment.