Overview of our Research Program
Liver cancer remains a devastating disease with poor survival outcomes, often arising in the setting of cirrhosis. The coexistence of chronic liver disease and cancer creates unique biological challenges that influence tumor progression and therapeutic response. Our research is driven by the need to understand this complex interplay at a mechanistic level to develop more effective treatment strategies.
We focus on identifying immune mechanisms that enable tumor persistence and recurrence, particularly in the setting of minimal residual disease following treatment. By studying how immune cells, especially macrophages, interact with tumor cells and contribute to therapy resistance, we aim to develop neoadjuvant strategies that eliminate residual cancer cells and prevent recurrence.
Looking ahead, our lab is expanding efforts to reprogram macrophages to enhance both innate and adaptive immunity against liver cancer. We are mapping spatial interactions within the tumor microenvironment to identify novel therapeutic targets that can disrupt immune evasion and metastasis. In parallel, we are improving mouse and patient-derived models to better translate preclinical discoveries into real-world therapies.
Ultimately, our goal is to develop more effective and personalized treatment strategies that not only extend survival but also improve quality of life for patients facing the dual burden of liver cancer and cirrhosis.
Ongoing Research
Determining how MASH Progresses to HCC
Metaolic dysfunction associated steatohepatitis (MASH) or fatty liver disease is an increasingly common precursor to hepatocellular carcinoma (HCC), yet the mechanisms driving this transition remain poorly understood. This project aims to:
• Investigate how chronic inflammation and fibrosis in MASH create a tumor-promoting microenvironment.
• Define the role of immune and stromal interactions in driving malignant transformation.
• Identify biomarkers that can predict patients at the highest risk of progressing from MASH to HCC, enabling earlier intervention.
Preventing Cancer Recurrence by Targeting Minimal Residual Disease
A major challenge in liver cancer treatment is the persistence of minimal residual disease (MRD) following surgery or locoregional therapies, leading to recurrence. This project focuses on:
• Unraveling how immune cells protect residual tumor cells from elimination.
• Developing neoadjuvant therapeutic strategies that can eliminate MRD before curative treatments.
• Exploring immune-based and targeted approaches to sustain long-term remission and prevent recurrence.
Dissecting Tumor Heterogeneity and Immune Evasion in human HCC
HCC exhibits high inter- and intra-tumoral heterogeneity, making it resistant to standard therapies. This project aims to:
• Map spatial interactions between tumor subclones, macrophages, and other immune cells within the tumor microenvironment.
• Identify how tumor heterogeneity contributes to immune evasion and therapy resistance.
• Use single-cell and spatial transcriptomics to uncover novel therapeutic targets for disrupting these adaptive mechanisms.
