Understanding tumor immune microenvironment heterogeneity and plasticity

We focus on Immune checkpoint blockade (ICB), which works by blocking cellular communication (ligand-receptor interactions) that affect the tumor-killing ability of T cells. Emerging evidence has shown the role of myeloid cells (with both pro- and anti- tumoral functions) in aiding ICB efficiency. We wish to identify the cross-talk between specific myeloid and T cell subsets that are involved in orchestrating the immune responses before and after ICB therapy.  We collaborate with oncology scientists, molecular and cancer biologists from the UW School of Medicine and Public Health to utilize preclinical cancer murine models and human samples to identify mechanisms of immunotherapy with single-cell technologies and analyses.

What is the role of neutrophils in cancer?

Neutrophils, the most abundant blood cell-type, have been found elevated in peripheral blood of cancer patients and associated with poor prognosis for multiple types of cancer. However, neutrophil heterogeneity and plasticity in the tumor microenvironment are not widely understood. We recently discovered an early unipotent neutrophil progenitor in human bone marrow marked by CD71 and CD117 with a potential protumoral function (Dinh et al., Immunity 2020).

We are curious about what types of neutrophils are derived from the neutrophil precursors and how they are diversified in circulation, at tumor and metastasis sites. We wish to answer the question if neutrophil subpopulations and their markers can predict cancer progression and response to treatments.

Developing bioinformatics methods

We are interested in developing computational tools to solve the biological questions we ask with special focuses on analyzing epigenomic (Whole Genome Bisulfite Sequencing), single-cell data, and integrated pipelines.

Epigenomics of myeloid cells

We use epigenomic (DNA methylome) as a window into the plasticity and multi-faceted roles of myeloid cells (focusing on neutrophils and monocytes) in homeostasis and how their fates changes in cancer and diseases.