Our laboratory is focused on improving treatment outcomes in breast cancer (particularly triple-negative breast cancer) as well as in other solid tumors through translational approaches. To accomplish this, we integrate data from genomic and molecular profiling studies with molecular biology and signal transduction methodologies to identify altered pathways in cancer, the functional consequences of these alterations, and ways to directly target them in patients to improve clinical outcomes and survival. These efforts span in silico (publicly available databases), in vitro (cell culture), in vivo (mouse and human clinical studies) and in situ (histology) methods.

There are several primary focuses of the laboratory:

1) How do tumor cells evade the immune system in cancer, and how can we target these mechanisms?

We have a strong interest in the intersection between new immunotherapies and tumor cell signaling pathways. We have identified several molecular pathways that are hijacked by tumor cells in order to suppress antigen presentation, which is required for effective immunologic elimination of tumor cells. Pharmacological inhibition of these pathways can restore antigen presentation, and potentiate anti-tumor immunity. However, the mechanisms by which tumor cells evade the immune system are largely unknown. The goal of this focus is to identify these mechanisms and validate approaches to inhibit them for the benefit of patients.

2) What molecular features or biomarkers can identify patients most likely to benefit from immunotherapy?

Immunotherapies have the potential to transform cancer therapy, but not all patients respond, and these drugs are incredibly costly and not without their toxicities (see #3). Thus, identifying patients most likely to benefit from immunotherapy early on, or a priori, could be incredibly valuable in triaging patients unlikely to respond to other therapies from which they are more likely to derive benefit. The discovery of molecular markers of response to immunotherapies is a major focus of the laboratory. We recently identified competence in class-II antigen presentation as a major predictor of outcome in patients treated with anti-PD-1 therapy, and are now exploring the functionality of MHC-II expression as a mediator of anti-tumor immunity.

3) What causes autoimmune-like toxicities in patients treated with immunotherapy?

As mentioned above, immunotherapies have the potential to cause rare, but severe toxicities, sometimes resulting in treatment-related mortality. Understanding the mechanisms behind immunotherapy-induced autoimmunity and the molecular features of patients who exhibit them is critical area of need. Through high level molecular profiling of peripheral blood, tumors, and immune-related adverse event-affected organs, we hope to uncover hints as to why some patients exhibit these toxicities, and try to model these toxicities in the laboratory.