University of Colorado School of Medicine

Dahl Lab

Using chromatin dynamics to better understand and treat pediatric brain cancers

One tissue section shown two ways at once: an H and E stain in pink and purple at the lower left gives way across a diagonal to a spatial transcriptomic map of the same section, in violet and orange, at the upper right.

About the lab

We study the biology of brain tumors in children, with the goal of finding better ways to treat them.

Our focus is on chromatin — the structure that packages DNA inside a cell and controls which genes get switched on. Childhood brain tumors are unusual in how heavily they depend on this machinery, and we think that dependence is also a weakness worth exploiting. We look at tumors one cell at a time to understand how they are organized, how they change under treatment, and where they might be vulnerable.

The point of the work is not the mechanism alone. Each of these questions is chosen because it might nominate a new target, a target that could become a therapy, tested in our models and, eventually, in trials for the children we treat.

Deconstructing tumors, cell by cell

Our lab uses advanced single-cell techniques to understand the biology underlying pediatric brain tumors. Where do they come from during brain development? How do they evolve under pressure from treatment? And how do they develop resistance to the therapies we use?

Learn more about single-cell work
Single-cell embedding of matched primary and recurrent tumours: many discrete islands of points, each colour a different patient sample, separated by open space.

The wiring and rewiring of tumor circuits

Cancer cells rely on complex epigenetic mechanisms to sustain and adapt their core transcriptional circuits. We use cutting-edge chromatin techniques to better understand these relationships and dependencies, and to look for new ways to disrupt them.

Learn more about chromatin and transcription
Multipanel genomics figure: a triangular Hi-C contact map across the MYC and PVT1 region, with called interactions circled, above stacked tracks for H3K4me1, H3K27ac, Myc binding and RNA-seq in control and treated conditions.

Discovery in a dish

We use both normal and cancer cells to model tumor biology, interactions with the microenvironment, and effects of treatment. How do cancer cells respond to disruptions of their core transcriptional circuits? Do dependencies exist that allow us to effectively kill tumor cells while sparing normal ones?

Learn more about our cell models
Fluorescence microscopy field showing dense green-labelled cells crossed by streaming red-labelled processes.
Second fluorescence microscopy field of the same preparation, shown smaller for comparison.

Modeling the next generation of therapy

We use sophisticated animal models to test promising cancer treatments. From intracranial drug infusions to CT-guided conformal radiation to volumetric MRIs, we use the most advanced techniques in neuro-oncology to prioritize new agents for clinical trials.

Learn more about preclinical therapy
Two images meeting at a gold line inside a circle. Above, a sagittal MRI of a mouse head showing bright lesions within the brain. Below, a CT section of the same anatomy with the radiation treatment volume shaded solid green.

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