April M. Weissmiller
Middle Tennessee State University, TN·Biochemistry
Many cancers are driven by MYC proteins, master switches that turn thousands of genes on or off. MYC itself has resisted decades of drug-making efforts because its shape offers no good pocket for a small molecule to grab.
- Fields
Biochemistry
Genetics
Pharmacology
- Topics
MYCN amplification
neuroblastoma
pediatric cancer
- Grants
- 2 known grants, through Jun 2028
What they work on
- Map which genes are bound and regulated by N-MYC and its partner proteins WDR5 and G9a in MYCN-amplified neuroblastoma cells, using genetic, genomic, and chemical-biology approaches to see how combined inhibition reshapes N-MYC-driven transcription.
- Test whether a single molecule can inhibit both WDR5 and G9a by using computationally driven drug discovery to identify and screen candidate dual inhibitors.
- Compare the effects of blocking WDR5 and G9a alone, in combination, or simultaneously on N-MYC function, to judge dual inhibition as a therapeutic strategy in neuroblastoma.
- Determine how MYC and the SWI/SNF chromatin remodeling complex jointly control genomic activity in diverse cancer cell lines lacking BRG1, the subunit encoded by SMARCA4, using genetic and genomic approaches.
- Test the hypothesis that BRG1 tempers MYC function across the genome, extending the lab's finding that the related SNF5 subunit directly antagonizes MYC at chromatin.
More about the research
An alternative strategy is to go after MYC's partner proteins instead: the helper molecules MYC recruits to reach specific genes. Work in this lab asks which partners matter in which cancers, how they reshape gene activity, and whether blocking them can shut MYC down. Two projects pursue this question in different tumor settings, one in a childhood cancer driven by extra copies of a MYC gene, the other in adult cancers that have lost part of a machine that repositions DNA packaging.
Why it matters
High-risk neuroblastoma with extra MYCN copies carries poor survival for young children even after aggressive therapy, and roughly one in five of all cancers carries a damaged SWI/SNF subunit. By testing whether MYC's helper proteins WDR5 and G9a can be blocked at once, this work could point toward a drug strategy for these children. The SWI/SNF studies could identify mechanisms that sustain SMARCA4-mutant tumors and suggest where to intervene.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Hamilton Hodges
Baylor College of Medicine, TX·Biochemistry
Determine how cellular signals influence which binding partners SWI/SNF chromatin remodelers (cBAF, PBAF, GBAF) select, using rapid perturbations in living cells with epigenomic and proteomic readouts.
Jiang Wu
University of Texas Southwestern Medical Center, TX·Neuroscience
Determine how phosphorylation of BRG1, a chromatin remodeling protein, triggered by neuronal activity primes enhancers of activity-regulated genes by setting up a cohesin-dependent folding of chromosomes in 3D.
Pin-Xian Xu
Icahn School of Medicine at Mount Sinai, NY·Genetics
Test whether removing Brg1, part of the Brg1-BAF chromatin remodeling complex, from Eya1-expressing inner ear progenitors at different stages closes off enhancers that guide sensory and neuronal fate.
The school
Middle Tennessee State University: 2 labs on PI Pages, $9M a year on research, 80 research doctorates a year.
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