The fundamental and translational research of Fabrice Lucien-Matteoni, Ph.D., is focused on understanding the tumor-intrinsic mechanisms of immune evasion and resistance to cancer therapies. His work serves as a scientific foundation for the development of novel targeted therapies and immunotherapies for the treatment of human cancers. In addition, Dr. Lucien-Matteoni develops noninvasive blood and urine tests that can facilitate cancer detection and prediction of response to specific therapies for individual patients.
Dr. Lucien-Matteoni's work in the Department of Urology at Mayo Clinic addresses critical unmet clinical needs in the management of urologic cancers (prostate, bladder and kidney) and pediatric rhabdomyosarcoma. His transformative research is multidisciplinary and involves surgeons, oncologists, pathologists, radiation oncologists and the biopharmaceutical industry to accelerate the bench-to-bedside translation of discoveries. Dr. Lucien-Matteoni's research covers multiple disciplines including molecular and cellular biology, cancer immunology, tumor metabolism, human-subject research, bioinformatics, and data science.
- Elucidating the cancer surfaceome to identify molecular determinants of immune evasion and resistance to therapy. To escape the immune system, cancer cells carry proteins on their surface that communicate negative signals to immune cells. These cancer-associated surface proteins are called the cancer surfaceome. Dissecting the mechanisms used by this cancer surfaceome to evade antitumor immunity offers opportunities for the development of novel therapeutics. Cell surface proteins are ideal targets for anticancer therapies, as their accessible extracellular domain makes any pharmacological intervention more effective. The cancer surfaceome also provides an alternative strategy to treat tumors with undruggable oncogenic alterations. Dr. Lucien-Matteoni's lab uses advanced proteomic methodologies, functional assays and animal models to characterize the identity and function of the cancer surfaceome.
- Dissecting the roles of tumor-derived extracellular vesicles (EVs) in tumor progression and response to anti-cancer therapies. EVs are microscopic particles (30 nanometers to 2 micrometers) released by all cells, including tumor cells. They contain molecular cargo such as DNA, RNA, proteins and metabolites that mirror their parent cells. While they have been originally described as "garbage bags" to remove cellular waste products, they also can serve as vehicles of intercellular communication. Importantly, tumor cells use EVs to generate an immunosuppressive microenvironment and resistance to therapies such as chemotherapy and radiation therapy, altogether supporting tumor progression. Dr. Lucien-Matteoni's lab uses nanotechnology and genetically engineered tumor models to understand the multifaceted role of tumor-derived EVs and develop therapeutic approaches to inhibit their function.
- Developing extracellular vesicle-based liquid biopsies for the management of urologic cancers. Obtaining a tissue biopsy of suitable quality from metastases is technically challenging, cannot be performed serially and does not capture intertumor molecular heterogeneity. To overcome this, Dr. Lucien-Matteoni's team explores the clinical value of tumor-derived EVs (tdEVs) as noninvasive cancer biomarkers. The lab has developed unique expertise in isolating and characterizing tdEVs using immunocapture methods and advanced flow cytometry. Dr. Lucien-Matteoni leads the biobanking of blood and urine from hundreds of patients with urologic cancers to evaluate the performance of tdEVs in cancer detection, prognostication and prediction of treatment response.
- Targeting tumor metabolism to tackle metastasis formation and drug resistance. The deregulation of cellular metabolism, known as metabolic plasticity, is a hallmark of cancer. It helps tumor cells sustain proliferation, resist cell death, avoid immune destruction and support metastasis. Dr. Lucien-Matteoni's work sheds light on the role of intracellular pH in metastasis formation and drug resistance. He developed several methods to monitor intracellular pH in real-time using fluorescence microscopy, and discovered the pH regulators NHE1 and NHE6 as two promising targets for anti-cancer therapies. A better understanding of the tumor metabolic microenvironment is needed to identify druggable molecular vulnerabilities that can help improve human cancer treatments.
Significance to patient care
Efforts by Dr. Lucien-Matteoni and his team are directed toward developing minimally invasive strategies for improving detection and monitoring treatment response in genitourinary cancers. In addition, a better understanding of tumor-intrinsic mechanisms of immune evasion and tumor progression paves the way for developing new therapeutic strategies and overcoming tumor resistance to conventional therapies.
- Excellence Through Teamwork Award, Mayo Clinic, 2022.
- Board member, Blood Task Force and Urine Task Force, International Society for Extracellular Vesicles, 2020-present.
- Member, American Urological Association, 2017-present.
- Member, American Association for Cancer Research, 2016-present.