Cancer Stem Cell
Cancer stem cell is a sub-population of cancer cells defined by sustained self-renewal, persistent proliferation, and tumor initiation capacity. Cancer stem cells play an essential role in tumor metastasis, recurrence, angiogenesis, chemotherapy and radiotherapy resistance, and immune evasion. Therefore, therapeutic strategies targeting cancer stem cells will bring new hope to the treatment of cancer. Dr.Xie and Xie Lab’s research focuses on the epigenetic(Cell, 2018), transcriptional(JCI, 2016), post-translational(Nature Neuroscience, 2015), and metabolic regulation of cancer stem cells（Cancer Discovery, 2019）; and more recently the crosstalk between cancer stem cell and the tumor microenvironment(Cell Research, 2020). These studies may permit targeted therapies or immunotherapies for cancer stem cells to improve cancer treatment.
Cancer is an ecosystem with cancer cells and their Tumor microenvironment (TME), which plays a critical role in tumor initiation, progression, metastasis, and immune evasion. Xie lab has developed a rapid three-dimensional (3D) bioprinting method to construct a glioblastoma (GBM) microenvironments model, which can represent cellular dependencies and immune interactions of primary tumor tissue(Cell Research, 2020). Recently, Xie Lab aims to utilize different models, including 3D bioprinting organoid and patient-derived xenograft (PDX), to study the interactions between different cell types of GBM TME, especially the tumor-associated macrophages (TAMs) and cancer cells. Meanwhile, Xie Lab is also interested in identifying novel molecules that can remodel TME. Targeting these molecules could enhance immune cells infiltration and inhibit tumor development and invasion. These studies may provide new insights into anti-tumor therapies.
Cancer immunotherapies aim to improve durable antitumor immune responses by manipulating the immune system to recognize and attack cancer cells. Although remarkable clinical success of chimeric antigen receptor-engineered T cell (CAR-T) in treatment of hematological malignancies has been achieved, the overall outcomes of CAR T-cell treatment solid tumors including GBM remain unsatisfactory. By using Whole Genome-wide CRISPR/Cas9 library Screening, we have successfully identified novel genes regulating CAR T cell anti-GBM activity (Cancer Discovery,2021). We aim to utilize high throughput screening ,single cell sequencing and other approach to further improve the anti-tumor activity of CAR T and other CAR-engineered immune cells including CAR-NK and CAR-Macrophage.
With development of new technology, bioinformatics analysis techology is also developing and we are able to understand biological process in increasing number of aspects. In Xie lab, we are utilizing single-cell RNA seq, single-cell ATAC seq, single-cell ChIP seq, along with WES, CRISPR screening, and other technologies to provide entry point for later verification experiments. Also, we are actively collaborating with other bioinformatics laboratories to dig deeper to learn more about generation and development of glioblastoma stem cell.