Wi Institute Medical Research
MS, 2007, Computer Science, Vietnam National University, Hanoi
Ph.D., 2012, Bioinformatics, University of Vienna, Austria
Postdoctoral research, Cancer Epigenomics, University of Southern California & Cedars Sinai Medical Center, Los Angeles, CA
Assistant Professor of Oncology
Cancer is a heterogeneous disease that complicates its study and therefore treatment. Immunotherapy has revolutionized cancer treatment but many patients still are faced with little or no clinical benefit with the same treatment. Recent high-dimensional technologies have allowed us the ability to understand the tumor ecosystem and its impact on treatment response. We are motivated by the question of how the tumor microenvironment changes upon cancer progress, before and after treatment. We follow a systems biology approach, using high-dimensional data from multi-omics genome-wide (genomics and epigenomics) and single-cell assays, data mining, and bioinformatics. We develop and employ computational biology methods to mine publicly available data and in-house generated data for the specific questions we ask.
1) How does the tumor immune microenvironment (TIME) influence immunotherapy? 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.
2) Can we predict cancer treatment outcomes based on blood-based biomarkers? Identification of predictive markers, especially by non-invasive approach, is an urgent need. We want to define specific immune signatures, with a strong focus on myeloid cells, from blood of cancer patients that can predict the outcome of immunotherapy. We will leverage high-dimensional immunoprofiling approaches with clinical trial samples from UW Carbone Cancer Center to identify the biomarkers that predict immunotherapy response and adverse effects.
3) 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. 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.
Ultimately, our goal is to understand how tumor immune microenvironment changes toward finding immunotherapeutic biomarkers and targets. Although our central questions focus on cancer, we are open to the collaborative environment in Madison to explore similar questions in other diseases.