To investigate how cancer-microenvironment interactions drive metastasis and therapeutic resistance, we have adopted and developed a series of unique animal models. We also implement interdisciplinary approaches through collaborations with experts with expertise in microscopy, bioengineering, chemistry, integrated omics, and clinical oncology. Our ultimate goal is to identify effective therapies to conquer metastasis, ideally by leveraging our own immune system.
Breast cancer bone metastasis
Using a series of unique models, we discovered the initial colonization of disseminated cancer cells requires the microenvironment niche comprised of cells of the osteoblast lineage. The cancer-niche interaction is mediated by heterotypic adherens and gap junctions, which activates the mTOR and calcium pathways in cancer cells to drive progression from single cells to multi-cell micrometastases. The cancer-niche interactions also render cancer cells more stem-like and capable for further dissemination to other organs. These studies advanced our understanding of bone metastasis and revealed potential therapeutic targets.
Immuno-regulation of metastasis and diversity of tumor immune microenvironment
The immune system is the major defense against tumorigenesis and tumor progression. However, many tumors acquire the ability to blunt or even invert the functions of the immune system. We are interested in the question of how breast cancers evolve to alter the immune system both systemically and locally. In particular, we aim to delineate how this is happening in the complex tumor ecosystems that differ between patients. The questions we are trying to attack include: 1) how the systemic and local immune environment varies among tumors of diverse genetic/epigenetic background; 2) how different tumors and immune cells co-evolve to develop diverse ecosystems; and 3) how to identify and target immune cell types/functions that confer therapeutic vulnerability in a specific tumor ecosystem. Our ultimate goal is to identify therapies that could restore the normal functions of the immune system.