Todd Waldman
Georgetown University, DC·Genetics
Glioblastoma multiforme (GBM) is the most common and deadliest tumor that starts in the brain. Many glioblastomas carry mutations that disable cohesin.
- Fields
Genetics
Biology
Biochemistry
- Topics
glioblastoma multiforme
brain tumor
cohesin
- Grants
- 1 known grant, through Jul 2027
What they work on
- Determine how STAG2-regulated chromatin loops, especially those anchored by CTCF and H3K27me3, control nearby gene expression in glioblastoma cells and tumors, using Hi-C, RNA-seq and the HiCorr/DeepLoop loop-detection pipelines.
- Compare gene-edited glioblastoma cells with repaired versus mutant STAG2 to test how this cohesin subunit sets the size and strength of individual DNA loops.
- Define how STAG2 loss increases Polycomb Group (PcG)-mediated chromatin looping and gene silencing, and how this links to the sensitivity of STAG2-mutant glioblastoma cells to PcG inhibitors.
More about the research
Cohesin is a ring of proteins that helps fold DNA into loops in 3D space. These loops connect enhancers, DNA switches that control genes, to the genes they control. STAG2 is the cohesin part mutated most often, accounting for more than half of cohesin mutations in GBM. However, no one knows how losing STAG2 helps tumors grow. This project, run jointly with the Jin lab, tests whether STAG2 mutations rewire DNA folding and gene silencing to drive GBM.
Why it matters
Patients with glioblastoma, the deadliest brain tumor, have few effective options. Explaining how STAG2 mutations change DNA folding and Polycomb gene silencing could show how cohesin-mutant tumors might be targeted therapeutically. The early observation that STAG2-mutant cells are sensitive to Polycomb inhibitors in culture suggests one possible direction.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Gilbert Rahme
Stony Brook University, NY·Genetics·Early-career
Model glioma-associated epigenetic changes in oligodendrocyte progenitor cells by disrupting the CTCF insulator near the PDGFRA growth gene and silencing the CDKN2A tumor suppressor.
Marcus Clark
University of Chicago, IL·Microbiology & Immunology
Define BRWD1's functions in germinal center B cells and test whether they depend on its conversion of static cohesin to dynamic, DNA-looping cohesin, using Brwd1 deletion.
Uttiya Basu
Columbia University, NY·Microbiology & Immunology
Test whether B cell development can be rescued in RNA exosome-deficient mice, and whether VDJ-carRNAs, chromatin-associated RNAs from the IgH locus, control VDJ recombination efficiency by the RAG enzymes.
The school
Georgetown University: 14 labs on PI Pages, $377M a year on research, 206 research doctorates a year.
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