PIPages
Labs

Hamilton Hodges

Baylor College of Medicine, TX·Biochemistry

Every cell has to decide which genes to switch on, and part of that decision depends on how tightly DNA is packed. SWI/SNF complexes are protein machines that use energy from ATP to loosen packed DNA (chromatin) so genes can be read.

Fields

Biochemistry

Genetics

Pharmacology

Topics

chromatin remodeling

BAF complex

neuroblastoma

Grants
2 known grants, through Apr 2030

What they work on

  1. 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.
  2. Identify the pathways that steer SWI/SNF complexes to particular regions inside the nucleus, using fast-acting chemical biology tools and live-cell microscopy.
  3. Define how SWI/SNF complexes coordinate with other chromatin regulators through non-catalytic interactions, meaning physical contacts rather than enzyme activity.
  4. Map how inhibiting SWI/SNF changes DNA accessibility, transcription and cell death at specific cell-cycle stages in neuroblastoma cells, after fast-acting inactivation of the SMARCA4 engine.
  5. Identify how SWI/SNF inhibition causes replication stress (trouble copying DNA) and cell-cycle deregulation that kill neuroblastoma cells near the G1-S boundary.
  6. Find synergistic combinations of clinical neuroblastoma drugs and SWI/SNF inhibitors in 2D cells and 3D spheroids, screening out those toxic to human neural crest cells and neurons, then validate them in an immune-competent mouse model.

More about the research

When these machines are misregulated they can drive disease, including childhood cancer. The lab studies both how cells control SWI/SNF activity in normal biology and whether blocking it can treat neuroblastoma.

Why it matters

Children with high-risk neuroblastoma have about a 50% five-year survival rate, and current intensive therapy can cause hearing loss, nerve damage and other lasting harm. Identifying drug combinations that exploit tumor dependence on SWI/SNF, while sparing normal neurons, could support clinical trials of more effective and less toxic treatments. More broadly, learning how cells control SWI/SNF may open new ways to steer gene expression in healthy and diseased cells.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Novel cellular regulatory mechanisms governing SWI/SNF activity

NIH · Aug 2020 – Apr 2030

Mechanisms and small-molecule targeting of SWI/SNF activity in neuroblastoma

NIH · Jul 2022 – Jun 2027

Closest labs

April M. Weissmiller

Middle Tennessee State University, TN·Biochemistry

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.

Shinya Watanabe

University of Massachusetts Chan Medical School, MA·Biochemistry

Define the roles of brain- and heart-specific DPF1 and DPF3 in the cBAF remodeling complex by rebuilding cBAF with DPF1, DPF2, DPF3 or no DPF protein and comparing nucleosome binding, sliding and ATPase activity.

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

Baylor College of Medicine: 38 labs on PI Pages, $881M a year on research, 115 research doctorates a year.

More about Baylor College of Medicine

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