During my training in the U.S., I focused on understanding the mechanisms driving adrenocortical carcinoma (ACC) aggressiveness and therapy resistance, including responses to immunotherapy. A major challenge in the field was the lack of a mouse model that could spontaneously develop ACC in an immune-competent environment—a critical tool for studying the disease.

To address this, I analyzed common genetic mutations in ACC patients and found that mutations in both the Wnt/β-catenin and p53 pathways were associated with more aggressive tumors and reduced patient survival. Working with Dr. Breault, I introduced these mutations into the adrenal cortex (ASCre/+::Trp53flox/flox::Ctnnb1flox(ex3)/+; BPCre), which led to the development of metastatic, hormone-producing ACC—the first genetically engineered model with these mutations that develops highly aggressive ACC. I also developed tumor-derived cell lines that can be used to generate allograft models of ACC.

This model faithfully replicates key molecular, hormonal, and cellular features of the disease, including glucocorticoid-producing tumors and lung metastases (Oncogene, 2020). It is the main animal tool used in my research and is now part of several collaborations investigating mechanisms of tumorigenesis and new therapeutic targets in ACC.

These models were critical to three recent studies in which I had the opportunity to collaborate with colleagues: (1) identifying a tissue-specific epigenetic vulnerability in ACC (Cancer Research, 2022); (2) demonstrating Dlk1 as a novel biomarker for predicting ACC malignancy (Cancer Communications, 2025); and (3) discovering that glutamine metabolism is a central metabolic dependency and therapeutic target in ACC (bioRxiv, 2025).