Explore Tumor Microenvironment and Metastasis

The lab may focus on studying how the tumor interacts with its surrounding microenvironment, including immune cells, blood vessels, neurons, and stromal components. This knowledge is crucial for identifying factors that promote tumor growth and metastasis, providing insights into how to disrupt these processes therapeutically.

Improve Therapeutic Strategies

Understanding the spatial pathology of pancreatic diseases allows for the identification of potential therapeutic targets, such as specific cell types, pathways, or tumor microenvironment features. The lab's goal is to inform people of treatment approaches that are more personalized and effective, based on the precise location and structure of disease processes.
 

Enhance Diagnostic Tools

The lab strives to develop and refine diagnostic techniques that can detect early-stage diseases by analyzing the spatial organization of tissues. This could involve the use of advanced imaging technologies, such as 3D reconstructions, to provide a more accurate diagnosis and identify key biomarkers associated with pancreatic disorders.

Identify Disease Mechanisms

By mapping the spatial patterns of diseases such as pancreatic cancer, and chronic pancreatitis the lab aims to uncover the underlying mechanisms of disease development and progression. This includes studying how tumor cells, inflammatory cells, or fibrosis are spatially organized and interact with other cells and tissues.

Advanced Preclinical Models for Therapeutic Discovery and Validation

To bridge discovery and clinical benefit, the lab develops and uses patient-derived organoids (PDOs). These 3D "mini-tumors" grown from a patient's own tumor tissue, overcome the limitations of traditional 2D cell lines. PDOs offer high fidelity, recapitulating the genetics, histology, and heterogeneity of the original tumor, and can be established with high success rates from small biopsy samples.

Interrogating Intratumoral Heterogeneity and Therapeutic Resistance

Tumor evolution, driven by intratumor heterogeneity (ITH) and phenotypic plasticity, is a primary cause of therapeutic failure. The Bailey Laboratory investigates the genetic and non-genetic mechanisms sustaining this diversity. Recent work from the Bailey and Corbo labs, published in Nature, has identified extrachromosomal DNA (ecDNA) as a major source of genomic heterogeneity and adaptability in PDAC. ecDNAs are small, circular DNA elements that exist outside of the chromosomes and can carry key oncogenes.

Developing a Spatial Omics Atlas of Pancreatic Cancer

The Bailey laboratory is using spatial omics technologies to build a high-resolution atlas of pancreatic cancer, conceptualizing the tumor as a pathological organ. These methods integrate molecular profiling with spatial tissue context, allowing for the analysis of gene expression, protein interactions, and metabolic states within their original architectural framework.

José Mário Leite

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