The Wnt5a-β-catenin Pathway Triggers a Metabolic Switch That Drives Indoleamine 2,3-dioxygenase Activity and Dendritic Cell Tolerization in the Melanoma Microenvironment.

We are interested in understanding the mechanisms that cancers have evolved to suppress the generation of tumor antigen-specific immune responses and how this knowledge can be exploited for the development of novel and more effective cancer immunotherapy strategies. This work involves the utilization of both autochthonous transgenic tumor model systems as well as clinical specimens to develop novel strategies to enhance the efficacy of immunotherapies while also developing predictive biomarkers to better guide the management of cancer patients with these agents. We strive to translate our understanding of the fundamental biochemical and metabolic pathways within the tumor microenvironment that are critical for driving immune evasion and resistance into early phase clinical trial testing.

Our work utilizes a variety of techniques and methodologies that span the breadth of basic biological research. This work integrates studies based on both 1) transgenic mouse tumor models that are monitored using bioluminescence and micro-CT imaging and 2) a variety of clinical specimens.

Our current areas of focus include:

1. Investigating mechanisms of adaptive or acquired immunotherapy resistance in cancer
2. Studying the relationship between EMT pathways and immunotherapy resistance.
3. Elucidating mechanisms of dendritic cell tolerization in the tumor microenvironment and how these processes may contribute to immunotherapy resistance
4. Development of novel pharmacologic and genetic strategies to overcome immunotherapy resistance
5. Investigating mechanisms contributing to select immunotherapy-associated toxicities