Trevor Deon Burt

Human Developmental Immunology: My research focuses on T cells, and how they function in the developing human immune system. Specifically, I am interested in how T cells are able to maintain immune tolerance to oneself, while also protecting against infection. By understanding these cells and their function, we hope to develop targeted therapies that will not only help to treat diseases that are caused by broken tolerance (e.g., autoimmune disease and transplant rejection), but also help newborn babies and older children to prevent and fight infections. 

My research has helped to demonstrate that fetal and adult T cells, though similar in phenotype, are functionally and transcriptionally unique. Compared to adult T cells, fetal naïve T cells are much more likely to differentiate into tolerogenic regulatory T cells (Tregs) and have a unique gene-expression profile, which was first discovered and described along with colleagues during my post-doctoral studies. Studies in my own laboratory are primarily focused on understanding both normal and pathological development of the developing human immune system, and understanding the mechanisms that lead to immune tolerance in utero. My lab recently employed single-cell and bulk RNA-seq, which we analyzed via a novel bioinformatics analysis and visualization pipeline (dittoSeq; with Drs. Dan Bunis and Marina Sirota at UCSF; Bunis DG, et al, Bioinformatics, 2020), in order to derive a gene signature assay that allows for determination of the relative abundance of fetal and adult T cells in neonatal blood (Bunis DG, et al. Cell Reports, 2021). We are interested in applying this signature to study the normal development and function of the immune system during the third trimester of human pregnancy, as well as how these normal processes are perturbed in the setting of preterm birth and intrauterine infection. I am concurrently studying signaling pathways and epigenetic modifications that are unique to T cells in early development in order to understand their predisposition to generate Tregs. Using ATAC-seq, RNA-seq, and ChIP-seq techniques, we discovered that the transcription factor Helios contributes to the tolerogenic nature of fetal and newborn T cells via their predisposition to differentiate into Treg cells (Ng MSF, et.al., Sci. Immunol., 2019). In the course of our studies to understand in utero inflammation, a pro-inflammatory population of innate-like CD4+ PLZF+ T cells in human prenatal gut was identified and characterized in my lab by Dr. Joanna Halkias, who demonstrated an expansion of these cells preterm labor and inflammatory gut pathology in the newborn (Halkias J, et al. J. Clin. Invest, 2019).

Current research projects in this area include broad screening of genes that area specific to the tolerogenic prenatal T cell population which may play a role in immune tolerance both in health and pathological states.

Environmental exposures during pregnancy and the development of childhood disease. Along with Dr. Kari Nadeau at Stanford University, we are studying the effects of environmental toxicant exposures during pregnancy on the immune system and health outcomes of women both during and after pregnancy. Specifically, my lab is interested in the epigenetic changes that occur in T cells, and the functional changes that may occur as a result of pollution exposure.