Chronic inflammation increases cancer risk and accelerates the progression of many malignancies, including those of the lung, stomach, liver and colon. Pro-inflammatory cytokines and tumor-infiltrating myeloid and immune cells play critical roles in all stages of cancer development. Immune infiltrates are evident in most, if not all solid tumors, including those that exhibit no pre-cancer inflammation. It is now clear that the process of tumorigenesis leads to changes in tumor cells and their microenvironment. Such changes shape the quality and magnitude of immune responses to tumors, resulting in the activation of tumor-promoting inflammation and suppression of anti-tumor immunity. The nature of tumor-immune interaction is therefore under intensive study in hope to understand how cancers arise and evolve, and how we can develop novel diagnostic and therapeutic tools for the benefit of human cancer patients.

Research in my lab focuses on the role of inflammation in colorectal cancer development and therapeutic intervention. Among them, IL-17 has been shown to play important roles in immunity against invading pathogens and in chronic inflammation of autoimmune diseases. IL-17 signaling also drives the development of colorectal, breast, pancreatic, and prostate cancers. Our and other people’s previous studies have shown that IL-17 signals to both tumor cells and their environment. Direct engagement of IL-17 promotes tumor cell proliferation and survival, whereas IL-17 signaling on stromal and immune cells seems to regulate tumor-associated inflammation and anti-tumor immunity. Our current study aims to address the relationship between IL-17 mediated inflammation regulatory T cell function in tumor development and immunotherapy. We also aim to interrogate the underlying mechanism by which IL-17 controls tumor Treg activity, in particular by regulating the expression and function of RNA binding proteins. 

We are also interrogating the involvement of inflammasome signaling in colorectal cancer. Our research shows a novel role of Gasdermin D in colon cancer development. Gasdermin D is an effector protein that mediates inflammasome-induced cell death, and its activation in colorectal tumors may have profound impact on the fate of tumor cells and the nature of tumor microenvironment. 

Research in my lab also focus on the generation of novel immune-oncology agents that effectively target and modify tumor microenvironment. These include the development and validation of novel oncolytic viral platforms that are cancer-specific, and invention and test of small molecule agents that target critical players in cancer immunotherapy.  

We are looking for highly motivated graduate students to join us and study the interaction between tumor cells and immune cells during tumorigenesis and cancer immunotherapy. 

Accepting Lab Rotation Students: Fall Block 2026, Spring 1 and 2 Block 2027

Our research aims to understand the role of inflammatory pathways in the development, immune regulation, and treatment of colorectal cancer. The study is comprised of the following projects:

1) Define the relationship between IL-17-mediated inflammation and regulatory T cell function in cancer: Our previous study showed that IL-17 signals directly to regulatory T cells and promote their immune suppression function. In the current project, we aims to interrogate the roles of RNA binding proteins, whose expression is regulated by IL-17, in Treg cells. We will employ multiple mouse models of tumorigenesis and cancer immunotherapy for this study, and explore the mechanism of Treg function change in the tumor environment using methods spanning cell biology to genomics. 

2) Elucidate the mechanism by which pyroptosis-induced GSDMD pore formation disrupts T cell function in tumor: Our current study show that human cancers predominantly exhibit activation of pyroptosis – leading to cleavage of the GSDMD protein and formation of membrane pore structures on tumor cells. Yet, genetic ablation of GSDMD from a mouse model of sporadic colon cancer reduced tumor load, suggesting an unexpected tumor-promoting function of this pyroptotic pathway. In this study, we aim to solve this puzzle and look into the interaction between tumor-cell mediated membrane repair and T cell function during tumor development and immunotherapy. 

3) Design of tumor-specific oncolytic viruses: The use of viral particles to treat cancer have met with limited success in the clinic. We aim to solve one of the major gaps in the field by developing a tumor-specific viral platform that delivers potent immune activating payloads following systemic injection. Our current data show that the “Cap-Linker” strategy we used to modify viral receptor protein significantly reduced its infection in normal tissues, enhanced its safety profile, and when coupled with a potent payload, eradicates most majority of established tumors in experimental animals. We aim to further enrich our pipeline in this field and provide a strategy for rationalized design of pro-drugs for cancer therapy. 

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