Metabolic Alterations in Prostate Tumorigenesis

The Loda laboratory has been focused on understanding the mechanisms responsible for metabolic rewiring in prostate tumorigenesis, with a specific interest in lipid metabolism and its regulation. The ultimate goal is to identify metabolic vulnerabilities that can be targeted therapeutically. Our approach is multidisciplinary, utilizing cell lines, orthotopic tumor xenograft, genetically engineered murine models and human tumors.

We have developed, pioneered and disseminated several techniques in molecular pathology, including multiplexed immunohistochemistry and in situ hybridization, ex vivo human tumor organotypic culture method to investigate antitumoral pharmacological properties that preserves the original cancer microenvironment. The landscape and related functional significance of genomic alterations in prostate cancer is studied in large, international cohorts such as the Prostate TCGA Consortium and the Pan Prostate Cancer Group that Dr. Loda co-leads.

The stroma is recognized as an important contributor in the process of carcinogenesis, and a driver of cancer progression. Experimental models demonstrate that altered stromal cells can induce tumor formation in non-cancerous prostate epithelial cells. It is also clear that the stroma morphologically and functionally changes in the presence of cancer. Despite the overwhelming evidence for the importance of the microenvironment in tumor progression, there is limited knowledge on its cellular composition and on how stromal cells signal to epithelial tumor cells, modifying their functional behavior. The Loda lab aims to construct a precise molecular and morphologic stromal map using laser capture microdissection, single cell RNASeq and multiplex immunofluorescence, in order to gain mechanistic insights as to the interaction between tumor cells and the stromal microenvironment that surrounds it.

Active Projects

• Pharmacologic inhibition of lipogenesis as therapeutic option for castration resistant prostate cancer
• Lipid Elongation via ELOVL5: A Novel Target for Advanced Prostate Cancer
• Functional atlas of mouse and human prostate cancer mesenchyme
• The role of TMPRSS2_ERG fusions in modulating tumor microenvironment in prostate cancer
• Metabolism rewiring by FASN inhibition alters cancer microenvironment
• The relative contribution of endogenous vs. exogenous lipids in prostate cancer
• Integrative genomics, transcriptomics, metabolomics, and histopathology studies in large prostate cancer cohorts
• Metabolomics of prostate cancer Gleason score in tumor tissue and serum
• Highly multiplexed spatial transcriptomics and proteomics