Inside the Wang Lab, we’re elucidating the immune suppressive tumor microenvironment to identify novel combination immunotherapeutic approaches to glioblastoma and GI metastases.
We’re also using synthetic lethality and monoclonal antibodies for cancer therapeutic development.
“Cancer doesn’t care whether you’re a physician, mathematician, bioinformatician or a biologist, pathologist, physicist, chemist, so let’s work together to bury it,” Dr. Wang said.
BSState University of New York at Stony Brook
PhDBoston University School of Medicine
PostdocHarvard Medical School, Leder Lab
Glioblastoma (GBM) remains the most lethal disease with a very dismal outcome. There have been many failed Phase III trials on both targeted therapy as well as immunotherapy.
We have recently developed several experimental approaches to tackle the complexity of GBM at the genomic, epigenetic and tumor microenvironmental levels. We will explore the state-of-the-art single cell sequencing technology (CosMx and 10X vasium platform) to elucidate the cell-cell interactions in the tumor microenvironment.
We have recently established a role of TBK1 in macrophage polarization, and we will further explore inhibiting TBK1 in sensitizing immunotherapy against GBM. EGFRviii is one of the most prevalent oncogenes for GBM but there is no targeted therapy available.
We have also established EGFRviii GBM animal model and the role of EGFRviii in tumor microenvironment remodeling and epigenetic landscape will be explored to define novel therapeutic approaches.
Because only a subset of cancer patients benefit from immunotherapy, there is a growing need to identify predictive biomarkers and intrinsic resistance mechanisms to improve clinical efficacy.
We recently developed a network approach which has successfully identified genes and pathways known to be associated with anti-PD1 response:
Five distinct cancer types (GBM, prostate, melanoma, colon, and pancreatic) will be screened by targeted CRISPR libraries in vivo for sensitizers to PD1 treatment. Additional bioinformatic approaches will be explored to identify sensitizers for other immune checkpoints.
Given the successful SE approach in targeting tumor suppressors, we have performed additional bioinformatic analyses and compiled a putative list of genes that we will screen for key tumor suppressor loss in major cancer types, including GBM, PDAC, prostate cancer.
We will further test whether such an approach can be extended to target oncogenic fusion events that are not druggable, such as the ETS fusions in the majority of prostate cancer patients. CRISPR screening will be performed followed by validation in appropriate animal models.
We have identified KDM5D as a male-specific gene which mediates Kras driven colon cancer metastasis (Li, et al, Nature 2023). We will elucidate the role of KDM5D in CRC progression and to define KDM5D target genes in mediating the metastasis process. We have also established KDM5D transgenic mice in a colon cancer model and its role will be further investigated in vivo.
In collaboration with Dr. Chun Li at MD Anderson Cancer Center, we will focus on the effect of irreversible electroporation on immunotherapy. We will explore a combination of IRE+PD1 +anti MDSC agents in a pancreatic cancer liver metastasis model. Tumor microenvironments will be studied post treatment using spatial transcriptomics.
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