Patrizia Mondello

Patrizia Mondello is a physician-scientist focusing on the biology and therapeutic targeting of B-cell lymphoma. She is currently an Advanced Oncology Fellow at Memorial Sloan Kettering Cancer Center (MSKCC) entering the second and final year of sub-specialization in lymphoid malignancies. Her clinical training and five years of postdoctoral research fellowship at MSKCC and Weill CornellMedical College have provided her with a unique set of skills and extensive expertise in B-cell lymphomas. The direct experience with patients has increased her curiosity to answer clinically relevant questions that are significant for improving the treatment of lymphoma. As a physician, she treats oncologic patients using standard and experimental therapies. As a scientist, she translates basic mechanisms into biomedically impactful findings. her fondness for both clinical and basic science has solidified her decision to pursue a career as a translational oncologist who is able to bring discoveries from the bench to the bedside. She trained in Medical Oncology at the University of Messina in Italy and was certified as an oncologist with the highest honors. Given her interest in the molecular mechanisms underlying cancer development, she decided to enroll in a PhD program in Cellular Biology and Experimental Medicine that she developed at MSKCC under the mentorship of Dr. Anas Younes, a leading translational researcher in the experimental lymphoma field. In Dr.Younes’ lab she has worked for three years on the development of novel targeted therapies aimed at disrupting well-defined oncogenic signaling pathways, including PI3K, BCL2 and NF-kB. My first work on CUDC-907, a dual PI3K and HDAC inhibitor (Mondello et al, Oncotarget 2017), helped provide data for FDA approval for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). She had the opportunity to give an oral presentation based on this work at the 2016 ASH Annual meeting and earned the 2016 ASH Abstract Achievement Award. She also discovered that histone deacetylase inhibition could downregulate expression of a mutated form of MYD88, a signaling adaptor that is frequently mutated in patients with B-cell lymphoma. She showed that this effect was dependent on transcriptional regulation of MYD88 through STAT3 and could enhance ibrutinib efficacy in MYD88 mutant cells (Mondello et al, JCI Insight 2017). This and two subsequent works (Liu Y* and Mondello P*, PNAS 2018; Derenzini E, Mondello P, et al, Cell Reports 2018) provided the mechanistic rationale for the development of ongoing clinical trials at MSKCC (NCT03939182, NCT01742988). To further build on her interest in lymphoma epigenetics, she pursued postdoctoral studies at Weill Cornell Medical College in the laboratory of Dr. Ari Melnick, a world-renowned expert in transcription and epigenetics. The focus of her postdoctoral research was aberrant epigenetic programming and development of precision guided therapies in B-cell lymphoma. Specifically, she explored the role of selective HDAC3 inhibitors in restoring antigen presentation molecules in lymphoma cells, enabling T-cells to recognize and kill them, especially in the presence of CREBBP mutations. This work led to a first-author paper in Cancer Discovery, and set the stage for the clinical development of this small molecule. She was also awarded the NIH/NCI Hemsley scholarship following this publication. She then enhanced her research skills related to cancer immunotherapy while studying the role of tumor-immune interactions as a research fellow at Mayo Clinic in the laboratory andclinic of Dr. Stephen Ansell, relevant investigator of immunotherapy and immune surveillance. She discovered that the expression of intrafollicular memory CD4+ T-cells is an independent predictor of outcome in follicular lymphoma (FL) and established a new risk model, termed BioFLIPI, that incorporates biological and clinical features to improve risk stratification for these patients. This work was selected as oral presentation at the 2019 ASH Annual meeting and recognized with the 2019 ASH Abstract Achievement Award and the 2020 ASCO Merit Award.

More recently, she has returned to MSKCC for further clinical training as an Advanced Oncology Fellow under the mentorship of Dr. Andrew Zelenetz, an internationally recognized leader in the lymphoid malignancies. Having spent the last year treating patients with Dr. Younes and Dr. Zelenetz, she has quickly honed her expertise in the treatment of B-cell lymphomas. She designed a clinical trial investigating the combination of HDAC3 inhibitors and venetoclax (a BCL2 inhibitor) in patients with FL and DLBCL based on her own preclinical data. She has had the unique opportunity to spearhead a multicenter study comparing the efficacy of R-CHOP vs R-Bendamustine in FL patients with high SUV at the baseline PET. Additionally, she has been awarded the NIH/NCI MSK Lymphoma SPORE Career Enhancement Award and led a major research effort between the MSK and Mayo Clinic Lymphoma SPOREs. This project will characterize the genetic landscape and microenvironment of the largely unknown FL3B, and ultimately lead to novel rationally designed clinical trials for patients with this aggressive lymphoma subset, helping to address an unmet medical need. Moreover, she was recently awarded the NIH/NCI K30 Clinical Research Methodology Curriculum Award and has pursued additional funding opportunities including the ASCO Young Investigator Award and the Lymphoma Scientific Research Mentoring Program by Lymphoma Research Foundation. Her career goal is to become an independent investigator in a leading academicresearch institution in the US where she can run an independent laboratory and maintain clinical activities as a medical oncologist. Her prior experience and current training will provide me with a solid foundation to reach her purpose of accelerating the translation of my scientific discoveries into novel treatment strategies to improve the cure rate of patients with B-cell lymphomas.