Summary
This project aims to understand breast cancer metastasis by investigating the cellular topography and function of the tumor microenvironment, focusing on glycan-dependent cell-cell and cell-extracellular matrix interactions and ECM remodeling.
What they want
The work involves using spatial transcriptomics, MIBI-TOF, and MALDI mass spectrometry on spatially-coregistered serial sections from breast cancer tissue blocks. The goal is to construct comprehensive single-cell maps, identify glycan-dependent interactions, map tumor and stromal cells, analyze immune evasion mechanisms involving tumor sialoglycans and macrophage-bound SIGLECs, and determine how collagen structure and function shift with enzyme activity (prolyl and lysyl hydroxylases) to promote metastasis. The clinical significance of these findings will be assessed against metastatic risk, stage, and IC subtype.
Deliverables
- Identification of glycan-dependent, cell-cell, and cell-ECM interactions that shift the TME toward tumor permissive states
- Comprehensive single-cell maps of tissue samples
- Mapping and enumeration of lineage and major functional subsets of tumor and stromal cells
- Identification of potential mechanisms of immune evasion involving tumor sialoglycans and macrophage-bound SIGLECs
- Correlation of spatial enrichment features with spatial transcriptomics data to identify regulatory glycosyltransferases
- Identification of how collagen type, hydroxylation, and crosslinking shift in coordination with neighboring cell populations
- Understanding how prolyl and lysyl hydroxylases drive structural changes in the ECM that promote BC metastasis
- Assessment of the clinical significance of extracted cellular and molecular definitions of ECM remodeling with respect to metastatic risk, stage, and IC subtype
Technical requirements
- Spatial transcriptomics
- MIBI-TOF
- MALDI mass spectrometry
- Spatially-coregistered serial sections from tissue blocks
- De novo proteomic and transcriptomic data analysis
- De novo imaging of tissue glycans
- Analysis of collagen type, hydroxylation, and crosslinking
- Focus on prolyl and lysyl hydroxylases activity
