Indiana University School of Medicine – Bloomington
Mechanisms of Cell–Microenvironmental Interactions in Cancer
We use quantitative, high-resolution imaging in 3D culture and zebrafish avatar models to ask how the tissue microenvironment drives cancer cell plasticity — and how that plasticity enables survival, adaptation, and therapy resistance.
Ewing Sarcoma cells display dynamics of active PI3K signaling organization
Research
Cancer cell plasticity is a key driver of disease progression, enabling metastasis and resistance to therapy — yet the mechanisms by which cancer cells sense and adapt to external cues remain largely unknown. This gap is especially critical in pediatric cancers, where a low mutational burden beyond a single driver oncogene often contrasts sharply with the variability seen in patient outcomes, pointing to non-genetic, microenvironment-driven mechanisms of adaptation.
Our work centers on Ewing Sarcoma (EwS), a pediatric cancer of bone and soft tissue, as a prototype for studying these questions. Traditional multi-omics approaches capture transcriptional states but often miss the cell-biological processes — membrane dynamics, cytoskeletal reorganization, spatial compartmentalization of signaling — that actually drive cell function. We address this by developing and applying quantitative live-imaging approaches that resolve cancer cell behavior directly, in physiologically relevant contexts.
High-resolution, high-throughput live imaging of human cancer cells xenografted into distinct tissue microenvironments in a living vertebrate.
Engineered extracellular matrix environments to dissect how specific cell–ECM interactions shape cell state and signaling.
Custom analytical pipelines that turn subcellular imaging data into quantitative, morphology- and signaling-based readouts of cell state.
We are asking how chromatin state contributes to Ewing Sarcoma plasticity, beginning with how EWSR1:FLI1 (EF1) activity differs across microenvironments. Live imaging of histones and histone acetylation markers lets us follow nuclear changes as cells shift between environments. Building on this, we are designing transcriptional reporters of EF1 targets to visualize EF1 activity states in vivo, in zebrafish, across different tissue contexts.
Changes in matrix composition and density alter cell shape, which shifts the polarization of Rac and with it the balance between cell migration and proliferation — a balance relevant to Ewing Sarcoma progression. We are perturbing Rac and Dia to dissect this pathway, defining the cytoskeletal regulators that translate ECM cues into cell state.
We are profiling differences in membrane composition between CD99-high and CD99-low Ewing Sarcoma states, using membrane dyes followed by lipidomics. Differences we identify are genetically perturbed to test their effect on cell phenotype, nominating membrane-regulating pathways that could be targeted therapeutically.
EwS cells form pseudorosettes — radially organized architectures seen clinically and in development — but only in specific tissue microenvironments, such as the zebrafish hindbrain ventricle. We are identifying the adhesion molecules that drive this tissue-specific self-organization, combining mosaic cell labeling with long-term light-sheet imaging to resolve their functional roles.
Together, these projects will define how microenvironmental cues orchestrate cell state transitions in cancer — building a foundation that extends beyond Ewing Sarcoma, and toward zebrafish patient-derived avatars for precision, context-aware cancer therapy.
People
Principal Investigator · Assistant Professor
The Segal Lab is opening at Indiana University School of Medicine – Bloomington in 2026. We are actively recruiting our founding lab members — see Join Us for opportunities.
Join Us
We are building our founding team and welcome inquiries from prospective graduate students, postdoctoral fellows, research associates, and undergraduate researchers who are excited about quantitative imaging, cancer cell biology, and in vivo model systems.
Publications
For a complete publication list, see Google Scholar or PubMed.
News
Welcome to the Segal Lab! We are opening our doors at Indiana University School of Medicine – Bloomington and recruiting our founding team.
Contact
Prospective students, postdocs, and collaborators are welcome to reach out directly.