Research
Cancer-Associated Fibroblast (CAF) metabolism
The Zanivan Laboratory studies the biology of cancer-associated fibroblasts (CAFs) in breast and ovarian cancer with the overarching goal of finding intervention strategies to target CAFs effectively to combat cancer in patients. In particular, the lab studies how cell metabolism contributes to defining CAF phenotypes and functions, including via epigenetic regulation. The overarching goal is to exploit these mechanisms to develop new therapeutic strategies to induce the formation of an anti-tumor microenvironment (TME) to block tumor progression and leverage the long-term benefit of immunotherapies.
The lab also investigates how diet can influence CAF metabolism and its functions. We focus on modulating levels of amino acid relevant to the production of the tumor extracellular matrix. The overarching goal of this line of research is to develop dietary intervention strategies to maximize the formation of an anti-tumor TME or maintain an anti-tumor microenvironment to prevent cancer.
How CAFs regulate the immune-TME is an emerging field of research. An immunosuppressive TME is a major barrier to effective checkpoint blockade immunotherapy, and CAFs are key regulators of this process. However, our limited understanding of CAF biology has been a barrier to the rational development of effective therapeutics that oppose their immunosuppressive functions.
The Zanivan Lab will tackle this question, focusing on CAF metabolism. Topics of interest include:
- Targeting proline metabolism to prime tumors to or synergize with immunotherapy treatments
- Developing optimal therapeutic intervention, including genetic, pharmacological and dietary approaches
- Understanding how the metabolic pathways associated with specific subsets of CAFs modulate their phenotype and immunoregulatory functions
- Developing new therapeutic intervention strategies to prime to or synergize with immunotherapy treatments or other treatments with long-term benefits on patients in epithelial ovarian cancer
Mass Spectrometry-Based Proteomics
The Zanivan Lab also develops innovative mass spectrometry-based proteomics workflows tailored to study the tumor microenvironment and cell metabolism. Their current goal is to develop cutting-edge spatial proteomic workflows and combine them with other spatial technologies to study CAF metabolism and the underlying molecular mechanisms in situ in patient tissue samples. Their overarching goal is to identify new mechanisms of immunosuppression that can be therapeutically targeted, as well as biomarkers to accelerate therapeutic decisions.
Recent breakthroughs in mass spectrometry (MS) technology have dramatically advanced the proteomic field, such that MS proteomics has been considered the next massive investment opportunity in biomedical research. The newest MS technologies coupled to microscopy and image-based single-cell isolation by high-resolution laser-capture microdissection enable spatial proteomic analysis of tissue samples. This year, spatial proteomics has been chosen as method of the year for exploring and mapping biological complexity by the journal Nature Methods.
The newest MS proteomics technology has also enabled to achieve cost-effective high throughput analysis of clinical samples that may aid clinical decision-making and showed that single-cell proteomics is now achievable. The Zanivan Lab will take advantage of cutting-edge MS technologies to advance their research. Topics of interest include:
- Developing spatial proteomics workflows to study stroma-immune interactions
- Integrating spatial proteomics with other cutting-edge spatial technologies to study cell metabolism at the cellular level in tissue samples