Patrizia Mondello, M.D., Ph.D., M.Sc., a physician-scientist in Mayo Clinic's Department of Hematology, is a recipient of the annual 2023 Gerstner Family Career Development Award from the Mayo Clinic Center for Individualized Medicine. The competitive awards advance innovative research to predict, prevent, treat, and cure diseases using individualized medicine. 

Inspired by a 20-year-old woman named Anna who died from an aggressive lymphoma, Dr. Mondello and her team are working on epigenetic precision therapy. This individualized treatment strategy aims to halt tumor development in follicular lymphoma, a blood cancer of the immune cells. A majority of people with follicular lymphoma have a good prognosis, but for the 20% of patients who experience an early relapse, their disease becomes increasingly resistant to therapy.

“The day before dying, Anna asked me to please find a cure to help her,” Dr. Mondello recalls. “Her words from more than 10 years ago continue to resonate in me.”

Recent research showed that when a gene called IRF4 is overexpressed, it disrupts key biological pathways, allowing lymphoma cells to proliferate and hide from the body’s immune system.

When Dr. Mondello and her team genetically silenced the IRF4 gene, it halted lymphoma growth and ultimately enabled the T cells of the immune system to recognize and kill lymphoma cells.

For this study, Dr. Mondello and her team will use CRISPR gene-editing along with genetically modified mouse models to understand how lymphomas with increased expression of IRF4 work at the molecular level. They will investigate how IRF4 controls the interaction between lymphoma B cells and the immune cells called T cells. They will also explore how IRF4 dictates the maturation stage of B cells — a disruption that makes the disease more aggressive.

Dr. Mondello says by understanding the mechanisms of IRF4 function, she hopes to identify new precision therapies that will ultimately reduce the need for chemotherapy, cause fewer adverse events and improve outcomes for more patients.

The Gerstner Family Career Development Awards are benefactor-sponsored to promote a specialized workforce for individualized medicine discovery, translation, and application. Made possible by a grant from the Louis V. Gerstner, Jr. Fund at Vanguard Charitable, the awards provide important seed money for early-stage investigators interested in launching a career in individualized medicine.

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