Kelsey Gallant

Program: Molecular Genetics and Genomics

Current advisor: Li Ding, PhD

Undergraduate university: Spelman College, 2018

Enrollment year: 2021

Research summary
Determinants of Therapeutic Response and Resistance Across Tumor Evolution, Microenvironmental Coupling, and Senescence in Breast Cancer

The goal of my research is to determine how tumor-microenvironment architecture and subclonal evolution jointly govern therapeutic response and resistance, using breast cancer, spanning triple-negative and luminal disease, as a primary model for high-heterogeneity solid tumors. This work is premised on the hypothesis that treatment response is a relational property of how tumor cell states and their local microenvironmental niches are coupled. Embedded within correlative studies of neoadjuvant chemo-immunotherapy and chemo-endocrine therapy, a central aim is to define the mechanisms that drive residual disease. By integrating single-nucleus RNA sequencing (snRNA-seq), spatial transcriptomics and proteomics, immunopeptidomics, and digital pathology across longitudinal pretreatment, on-treatment, and surgical timepoints, this work examines tumor-stromal-immune organization that distinguishes response from resistance is established and remodeled under therapy. Pairing these data with whole-exome sequencing links somatic and germline variants and subclonal architecture to the phenotypic plasticity and microenvironmental remodeling that shape tumor dynamics, distinguishing genetically selected from non-genetically adapted resistance. These findings are extended across a cross-sectional cohort of over 800 patients to test their generality, with the goal of identifying prognostic markers, genomic vulnerabilities, and candidate therapeutic targets.
A complementary line of work examines cellular senescence, a state of stable cell-cycle arrest, as a determinant of breast cancer outcomes, comparing chemotherapy-treated and treatment-naive tumors. These analyses suggest that chemotherapy-induced senescence reshapes the tumor microenvironment, nominating senescence-associated changes as candidate prognostic biomarkers and therapeutic targets. Across these efforts, I integrate multimodal single-cell, spatial, genomic, and histologic data to connect tumor-intrinsic genetic evolution and phenotypic plasticity with the microenvironmental organization that determines treatment outcome. Collectively, this research seeks to define the genomic and microenvironmental determinants of therapeutic response and to advance more precisely tailored treatment strategies for high-heterogeneity solid tumors.

Graduate publications