Newton-Abraham Lecture 2023
Professor Massimo Loda, Newton-Abraham Visiting Professor at Oxford University
Wednesday, 20 September 2023, 5pm to 6pm
Tsuzuki Lecture Theatre, St Anne's College, 56 Woodstock Rd, Oxford OX2 6HS
'Lipids in prostate cancer pathobiology: friends and foes'
Professor Massimo Loda, the David D. Thompson Professor and Chairman of Pathology and Laboratory Medicine at Weill Cornell Medicine and Pathologist-in-Chief in the New York-Presbyterian-Weill Cornell Campus, will give the 2023 Newton-Abraham Lecture on Wednesday 20 September at 5pm.
The lecture will be followed by a drinks reception in the foyer of the Ruth Deech Building.
Booking is required and admission is free. Please register by Friday 15 September.
Professor Massimo Loda is the David D. Thompson Professor and Chairman of Pathology and Laboratory Medicine at Weill Cornell Medicine; and Pathologist-in-Chief in the New York-Presbyterian-Weill Cornell Campus. For many years, he has served as a Senior Staff Pathologist at Brigham and Women’s Hospital, and Chair of the Department of Oncologic Pathology at Dana-Farber Cancer Institute. Furthermore, he is Professor Emeritus of Harvard Medical School and Newton-Abraham Professor at the University of Oxford, Lincoln College, UK. Professor Loda directed molecular pathology laboratories in various institutions and served as interim director of molecular pathology at Weill Cornell Medicine-Presbyterian Hospital. He has worked as a physician-scientist, performing clinical work as a genito-urinary pathologist as well as a molecular pathologist. For years, his laboratory has focused on metabolic alterations in prostate tumorigenesis, with specific interest in lipid metabolism and its regulation. This has lead to the identification of potential vulnerabilities in the metabolic reprogramming of lipid synthesis that occurs in tumors in general and in prostate cancer in particular. Clinical trials with inhibitors of the rate limiting Fatty Acid Synthase enzyme are currently underway. His approach is multidisciplinary, utilizing cell lines, orthotopic tumor xenograft, genetically engineered murine models, and human tumors.
Education Honours and Awards
Professor Massimo Loda was a medical student at the University of Witwatersrand in Johannesburg, South Africa and completed his medical degree and residency in Surgery at the University of Milan. Professor Loda also completed a residency in anatomic pathology at Deaconess Hospital, Harvard Medical School. His post- doctoral fellowship at the New England Medical Center at Tufts University focused on molecular pathology, a nascent discipline at the time. He received the Barr-Weaver Investigator award from Dana Farber Cancer Institute in 1998 and the Donald S. Coffee Physician-Scientist Award from the Prostate Cancer Foundation in 2003. He also received knighthood from the Italian Government in 2015 and was accepted as member of the Association of American Physicians that same year. He became the chair of the Pathology Task Force at the American Association of Cancer Research (AACR) in 2018. He was nominated the Newton Abraham Visiting Professor at the University of Oxford-Lincoln College, commencing in 2021. This year he has been awarded the Professorship in Network Oncology and Precision Medicine from the University of Rome, the William O. Russell Award from MD Anderson Cancer Center, Houston, TX, the AACR Team Science Award and the Society for Basic Urologic Research (SBUR) Meritorious Achievement Award.
Contribution to Science
Metabolism and prostate cancer. Genetic alterations in cancer define specific metabolic pathways that support their survival and growth. Thus, simultaneous targeting of selected metabolic enzymes and “driving” oncogenes may be cancer cell-selective. Dr. Loda discovered that USP2a stabilizes fatty acid synthase (FASN) by preventing its degradation and showed that FASN is a “metabolic oncogene”. He further demonstrated that USP2a behaves as an oncogene in prostate cancer and that it enhances c-Myc expression via the modulation of specific subsets of microRNAs. The Loda lab also showed that USP2a localizes to early endosomes antagonizing EGFR endocytosis. This could be exploited therapeutically in cancers over-expressing EGFR. Significant interactions between body mass index, FASN polymorphisms and FASN expression suggest FASN as a potential link between obesity and poor prostate cancer outcome. We found that both the energy sensor AMPK, a master regulator of metabolism and lipogenesis, and FASN, the rate-limiting enzyme for de novo lipogenesis characteristic of many tumors, represent ideal targets in prostate cancer. Inhibition of lipogenesis results in downregulation of both the androgen receptor and its ligand-independent V7 splice variant, and this is actively being exploited therapeutically. As mentioned above, clinical trials are ongoing with inhibitors of this enzyme.
Cell cycle regulation in cancer. Professor Loda has been interested in the dissection of the pathways leading to altered cell cycle regulation in human solid tumors. He was the first to discover a tumor-specific proteolytic mechanism targeting p27 in colon tumors and establishing the loss of this cyclin-dependent kinase inhibitor as a powerful prognostic maker in many human cancers. Investigating ties between cell cycle control and metabolism, he showed that fatty acid synthesis is required at the G2/M transition and represents a novel “lipogenic checkpoint” and may be therapeutically exploited with FASN inhibitors or AMPK activators.
Methods in molecular pathology to classify prostate cancer. He has developed molecular pathology techniques such as ex vivo organotypic cultures, multiparametric in situ analysis, advances in image analysis, novel algorithms used in digital pathology, metabolic profiling in formalin-fixed, paraffin-embedded tissue, discovered of p63 as a diagnostic marker in prostate cancer, and contributed to the molecular classification of prostate cancer as co-leader of the Prostate TCGA Consortium. He is currently working on the molecular landscape of tumor stroma in prostate cancer by single cell RNASeq.