Spatiotemporal mapping of tumor microenvironment evolution

The National Cancer Institute awarded Whitehead Institute for Biomedical Research $141,750 on July 7, 2026, under the Cancer Research Manpower program (CFDA 93.398) to support spatiotemporal mapping of tumor microenvironment evolution through development and application of PETRACER, a prime editing-based evolving lineage tracing system that enables simultaneous profiling of cell state and lineage with spatial context.

The recipient will map tumor-specific T cell recruitment and differentiation dynamics during tumor progression and perturb candidate regulators to uncover molecular mechanisms driving differences in T cell function and persistence in tumors. During the K99 mentored phase, the principal investigator will gain advanced training in in vivo lineage tracing, genetic perturbations, and spatial profiling from experts in CRISPR-based genomic technologies, genetically-engineered mouse models, and imaging. During the subsequent R00 independent phase, the work will expand to study how perturbations alter T cell lineage dynamics and how the broader tumor microenvironment changes during cancer progression and therapy.

The award supports research at Whitehead Institute in Cambridge, Massachusetts, with a period of performance through June 30, 2028. This assistance type is a project grant under the Cancer Research Manpower program, which provides biomedical training opportunities for individuals pursuing careers in basic, clinical, and prevention research important to the National Cancer Program.

Abstract

Cancer progression and therapeutic response are strongly influenced by the immune system, particularly the behavior of t cells within the tumor microenvironment. Despite the success of immunotherapies such as immune checkpoint blockade, clinical responses remain variable due to incomplete understanding of the dynamic, context-dependent behavior of immune cells. A major GAP exists in our ability to resolve the spatiotemporal lineage and phenotypic dynamics of tumor-infiltrating immune cells in vivo, which limits our ability to identify key windows and mechanisms for therapeutic intervention. To address this, i have developed petracer, a novel prime editing-based evolving lineage tracing system that enables simultaneous profiling of cell state and lineage with spatial context. This proposal aims to apply petracer to dissect the lineage, differentiation, and migration dynamics of immune cells during cancer progression. During the K99 mentored phase, i will map tumor-specific t cell recruitment and differentiation dynamics during tumor progression and perturb candidate regulators to uncover molecular mechanisms that drive differences in t cell function and persistence in tumors. Through this work, i will gain advanced training in in vivo lineage tracing, genetic perturbations, and spatial profiling from experts in crispr-based genomic technologies, genetically-engineered mouse models, and imaging. This training will complement my background in genomics and cancer immunology and prepare me to launch an innovative independent research program. In the R00 independent phase, i will expand this work to study how perturbations alter t cell lineage dynamics and how the broader tumor microenvironment changes during cancer progression and therapy, integrating tools and insights developed during the mentored phase. The transition will mark the establishment of my independent research group focused on understanding immune responses in cancer to inform rationale therapeutic strategies. Together, this proposal will uncover key principles of immune cell plasticity and tumor microenvironment dynamics, while equipping me with the skills, data, and models needed to lead an impactful independent lab at the intersection of cancer immunology and systems biology. This project involves the use of animal models in order to study the complex interactions between cancer cells and the surrounding microenvironment over time, which cannot be adequately modeled using in vitro systems.