Patrizia Mondello, M.D., Ph.D.

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SUMMARY

Patrizia Mondello, M.D., Ph.D., researches the role of epigenetic alterations in B-cell malignancies and the impact on the tumor microenvironment. She combines genomic, epigenomic and transcriptomic profiling approaches to patients with lymphoma and genetically engineered lymphoma cell lines with transgenic mouse models.

Dr. Mondello's team strives to identify and functionally characterize recurrent genetic lesions affecting chromatin modifiers and transcription factors. She seeks to determine the role of these genetic alterations in reprogramming B cells to undergo malignant transformation and modulate the tumor immune crosstalk. Ultimately, the role of this genetic information may develop specific and potent therapeutic strategies.

Focus areas

• Crosstalk between malignant B cells and the tumor microenvironment in B-cell lymphoma. Dr. Mondello identified IRF4 as a critical regulator of immune signaling in the germinal center B cells. Dr. Mondello strives to elucidate the mechanisms by which malignant B cells, differently expressing IRF4, may reshape the lymphoma tumor microenvironment and define the immune phenotype associated with IRF4 signature.
• Transcription factors orchestrate alternate B-cell fates and dysregulation promotes lymphomagenesis. Dr. Mondello's preliminary work identified an inverse correlation between IRF4 and BACH2 in human lymphoma and murine germinal center B cells. She examines their antagonistic function in controlling the exit of B cells from the germinal center and clarifies whether and how the subversion of their balance promotes an aggressive form of lymphoma.
• Cell-of-origin and immune microenvironment of FL3B. FL3B is a rare subtype of follicular lymphoma. Preliminary work from Dr. Mondello's team defined a clinical and phenotypic distinction between two FL3B subpopulations. Dr. Mondello seeks to uncover the distinct molecular and immune features of FL3B. These features of FL3B may provide the rationale for precision medicine to restore antitumor immunity in the unfavorable category of patients with lymphoma.
• Intrafollicular CD4+ memory T cells in follicular lymphoma. Prior work from Dr. Mondello's team demonstrated the prognostic value of CD4+ memory T cells, which play a critical role in immune surveillance. Her team developed a bio-clinical risk model, termed BioFLIPI, that offers improved risk stratification in follicular lymphoma. Dr. Mondello now plans to determine whether the lack of CD4+ memory T cells is determined by altered transcriptional programs in malignant B cells, if it is associated with a broad immune dysfunction in the tumor microenvironment and may it favor transformation to an aggressive lymphoma.
• Cooperations in Waldenstrom macroglobulinemia and the tumor microenvironment. Preliminary work from Dr. Mondello's team identified two putative major oncogenic cooperations in Waldenstrom macroglobulinemia. Dr. Mondello now seeks to define the biologic impact of these alterations in Waldenstrom macroglobulinemia and uncover how they may reprogram B cells and influence changes in the tumor microenvironment.

Significance to patient care

Most B-cell lymphomas are caused by changes in transcription factors and chromatin modifier genes. Transcription factors affect genetic information. Dr. Mondello's research may provide unique biological insights into the unusual epigenetic mechanisms driving the growth and development of lymphomas and the communication between B and T cells. Dr. Mondello's work may lead to more effective treatments for B-cell lymphomas.

Professional highlights

• K08 Mentored Clinical Scientist Research Career Development Award, National Institutes of Health and National Cancer Institute, 2024-2029.
• American Society of Hematology:
  • Junior Faculty Scholar Award, 2024-2026.
  • Translational Research Training in Hematology scholar, 2023.
  • Abstract Achievement Award, 2016, 2019, 2020, 2022.
• Clinical Investigator Career Development Award, Lymphoma Research Foundation, 2023-2026.
• Immune Aging Award, for “Clonal Plasma Cell Disorders Drive Chronic Immune Activation Leading to Accelerated Biological Aging,” Department of Immunology and Robert and Arlene Kogod Center on Aging, Mayo Clinic, 2024.
• Young Investigator Award, Society of Hematologic Oncology, 2022-2023.
• American Society of Clinical Oncology:
  • Young Investigator Award, 2021.
  • Merit Award, 2020.
• Under 40 in Hematology Award, Italian Society of Hematology, 2021.
• Young Investigator Award, the Paola Campese Award for Research in Hematologic Malignancies, Italian Scientists and Scholars in North America Foundation, 2020.