Summary

The National Cancer Institute awarded a $178,000 Project Grant under the Cancer Biology Research program (CFDA 93.396) to Boston Medical Center Corporation on June 11, 2026, with a completion date of May 31, 2028. This research project aims to develop a cost-effective, scalable methodology to decode the tumor microenvironment (TME) in triple-negative breast cancer (TNBC) by integrating advanced spatial sequencing technologies including spatial Assay for Transposase-Accessible Chromatin with sequencing (ATAC-seq), spatial in situ transcriptomics (Xenium), and single-nucleus epigenetic multiome sequencing. The primary deliverable is the creation of a comprehensive, patient-specific spatial regulatory atlas of TNBC that maps gene regulatory networks within intact tissue samples obtained from core-needle biopsies.

The research is structured in two main aims: Aim 1 focuses on establishing an optimized multi-modal workflow that maximizes molecular insights from limited biopsy material through tissue-preserving and multiplexed sequencing approaches, leveraging patient-specific genetic variation for data deconvolution; Aim 2 involves developing a computational framework to integrate these multi-layered datasets and identify key regulatory chromatin elements and transcriptional programs associated with TNBC progression, immune infiltration, and therapy resistance. The anticipated products will provide fundamental insights into epigenetic plasticity and spatial organization within the TNBC microenvironment, addressing critical knowledge gaps in intra-tumor heterogeneity and mechanisms underlying immune evasion and therapeutic resistance.