Michele Anderson
PhD
Research Interests
Our laboratory studies how transcriptional regulatory networks control cell fate decisions during development and regeneration. We are particularly interested in how transcription factors interact with extracellular signals and chromatin state to establish developmental identity, restrict alternative cell fates, and enable cells to respond to changing physiological environments.
T cell development provides our primary model for investigating these questions. Our work focuses on the E protein transcription factor HEB (Tcf12) and its two isoforms, HEBAlt and HEBCan. We discovered HEBAlt and have shown that it performs functions distinct from HEBCan during early T cell development, including suppression of alternative lineage choices and regulation of T-lineage genes. We are now investigating how HEBAlt and HEBCan cooperate with other transcriptional regulators and developmental signals to control T-lineage commitment and the subsequent choice between αβ and γδ T cell fates. Using complementary genetic models together with transcriptomic, chromatin-accessibility and transcription-factor occupancy approaches, we aim to understand how regulatory networks are reorganized as cells transition between developmental states.
A broader goal of our research is to identify general principles governing developmental transitions and cellular plasticity. We are integrating gene expression and chromatin data to investigate how regulatory-element architecture contributes to the establishment, maintenance and redirection of developmental trajectories. We are also extending these concepts to adult mesenchymal progenitor cells, asking how transcriptional and chromatin regulatory mechanisms control alternative cell-fate choices during homeostasis and tissue regeneration.
Our studies of γδ T cell development have additionally led us to investigate how immune signals influence skeletal muscle regeneration. HEB-dependent developmental pathways regulate the generation of IL-17-producing γδ T cells, providing unique genetic models for examining the consequences of altered early IL-17 responses following tissue injury. We are investigating how IL-17-dependent signals are interpreted by muscle stem cells and stromal populations and how the timing and duration of inflammatory signals influence the transition from injury to tissue repair.
Across these systems, our central question is: how does a cell interpret its regulatory environment to decide what it will become?
Selected Publications
https://doi.org/10.7554/elife.109197
https://doi.org/10.1080/10985549.2025.2505730
https://doi.org/10.3389/fimmu.2022.848577
https://doi.org/10.1016/j.celrep.2021.109227
https://doi.org/10.1038/s41467-017-02225-5
https://doi.org/10.1016/j.stemcr.2019.11.003
https://doi.org/10.1016/j.stemcr.2017.07.011