Immune cells perform an array of complex and coordinated functions, leading to immune-mediated protection from infection, local response to and repair of injuries, and homeostatic tissue maintenance. Building a complete systems level understanding of immune cell function is essential to identify the myriad of factors that promote proper or aberrant immune responses. Research in this area of the lab focuses on understanding cells like macrophages and T cells in native tissues and how their fates and functions are altered by signals from the endocrine system and the local tissue milieu. Our current efforts are focused on systematically mapping how hormones impact macrophages. By understanding cells in their in vivo state and how they respond to perturbations ex vivo, we can identify the drivers of disease processes, nominate therapeutic targets, and identify new methods for modulating immune cell behaviors in hormonally-controlled processes. This ultimately will create opportunities to engineer immune behaviors to promote health.
There is a need to create versatile tools for exploring the interplay between peripheral, tissue and immune factors in tissue remodeling and disease. Additionally, systems that faithfully recapitulate key structural and molecular features of human physiology are essential to test hypotheses and nominate/screen for therapeutics. We meet this need by engineering, validating, and manipulating ex vivo models, for example, as organoids, ex vivo cultures, or co-cultures. Current systems in the lab include developing models for healthy human lactation and breast tissue remodeling, understanding endometrial cancer, and working collaboratively as part of the Ovarian Contraceptive Discovery Initiative for the identification of non-hormonal contraceptives via targeted transcriptomics. Our ultimate goal is to develop and leverage these systems for translational benefit.
We generate and use large-scale datasets with high-resolution methods, like single-cell RNA-sequencing (scRNA-seq), to create an integrated understanding of overall health. When combined with novel computational methods and longitudinal sampling, we can identify markers of systemic and local tissue health. We apply these approaches across many areas, with the overarching goal of better defining how peripheral features correlate with reproductive and uterine health, and ultimately, long-term health outcomes. For example, maintaining immune tolerance during pregnancy is essential and evidence suggests that imbalances between T cell subsets can lead to fatal pregnancy events. Additionally, systemic immunity can be altered over the course of the menstrual cycle given variations in flare-ups in autoimmune diseases.