Matthew Waitkus
Duke University, NC·Medicine & Clinical Research
Some brain tumors stay alive and keep dividing by using an unusual trick to protect the ends of their chromosomes. They also tend to escape the immune system.
- Fields
Medicine & Clinical Research
Microbiology & Immunology
Genetics
- Topics
glioma
IDH-mutant astrocytoma
brain tumors
- Grants
- 2 known grants, through Mar 2031
What they work on
- Define how SMARCAL1, a helicase that restarts stalled DNA copying, limits ALT telomere synthesis, replication stress and genomic instability in IDH-mutant astrocytoma cells, using inducible SMARCAL1 depletion.
- Test whether targeting SMARCAL1 combined with vorasidenib, an FDA-approved IDH inhibitor, slows tumors and stimulates anti-tumor immunity in glioma models with intact immune systems.
- Determine how loss of ATRX, a DNA-packaging protein, switches on type I interferon and other inflammatory signaling inside glioma cells.
- Test whether ATRX loss and the partner IDH1 R132H mutation shape anti-tumor immunity and response to dsRNA agonists, virus-mimicking immune drugs, in preclinical mouse glioma models.
- Determine whether dsRNA-based therapies trigger inflammatory activation in lower-grade gliomas.
More about the research
Both problems help explain why these tumors keep coming back after surgery, radiation and chemotherapy. This work studies IDH-mutant astrocytomas and related gliomas, which are incurable brain tumors. These tumors often carry mutations in three genes: IDH1, ATRX and TP53. The two projects ask how ATRX loss changes tumor biology, and how those changes could be turned into treatments. One project targets how the tumors maintain their chromosome ends. The other targets how they interact with the body's built-in, fast-acting immune defenses.
Why it matters
Patients with IDH-mutant astrocytomas and other gliomas usually relapse, and no approved therapy targets ALT. These projects could identify SMARCAL1 as a treatment target for ALT-positive brain tumors and other ALT-positive cancers. They could also support combining SMARCAL1 targeting with vorasidenib, or using dsRNA-based immune agonists for ATRX-mutant gliomas. Both strategies may turn the tumors' own weaknesses into ways of triggering anti-tumor immunity.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Charles Reynolds
Texas Tech University Health Sciences Center, TX·Medicine & Clinical Research
Test whether telomere dysfunction drives high ATM kinase activation, a DNA-damage alarm signal, across ALT+ cancers of many types, using patient-derived cell lines and mouse xenografts compared with telomerase+ models.
Alexander Stegh
Washington University in St Louis, MO·Pharmacology
Determine the cellular, epigenomic, and metabolic mechanisms by which wild-type IDH1 keeps tumor-associated myeloid cells immunosuppressive, using mice in which the enzyme is switched on or deleted only in myeloid cells via tamoxifen-induced LysM-creERT2 recombination.
Kwok Kin Wong
New York University, NY·Medicine & Clinical Research
Determine how co-mutations such as MYC, KMT2D, STK11 and PTEN change SCLC plasticity (cells' ability to switch identity) and transcriptional subtypes, using new mouse models built on TP53/RB1-mutant SCLC.
The school
Duke University: 61 labs on PI Pages, $1.6B a year on research, 417 research doctorates a year.
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