Charles Reynolds
Texas Tech University Health Sciences Center, TX·Medicine & Clinical Research
Cancer cells must keep rebuilding telomeres, the protective DNA caps at the ends of chromosomes, or they stop dividing. Most cancers do this with telomerase, an enzyme that adds telomere repeats.
- Fields
Medicine & Clinical Research
Pharmacology
Genetics
- Topics
telomeres
telomerase
C-circle assay
- Grants
- 2 known grants, through Aug 2027
What they work on
- 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.
- Determine whether the ATM inhibitor AZD1390 or the p53-restoring drug APR-246, combined with irinotecan chemotherapy, kills ALT+ cancer models more effectively than telomerase+ models, and whether AZD1390 reverses irinotecan resistance.
- Test the hypothesis that ALT+ cancers tolerate ATM activation because p53 is broken, and that p53 restored by APR-246 is switched on by ATM, making ALT+ cells selectively vulnerable.
- Define how tissue collection, storage, sample amount and nucleic acid quality affect TERT mRNA qPCR and the C-circle PCR assay used to classify tumors by how they maintain telomeres.
- Develop and validate a plasma C-circle assay that detects ALT cancers from tumor DNA circulating in the blood, and complete CAP/CLIA certification studies so both assays can be used in clinical labs.
More about the research
A minority use a backup route called Alternative Lengthening of Telomeres (ALT), which copies telomere DNA by recombination, a DNA-swapping repair process. ALT-positive (ALT+) cancers tend to resist chemotherapy and have poor outcomes. The two projects here aim to find which tumors use ALT and to find drugs that exploit ALT's weak points.
Why it matters
Patients with ALT+ cancers, including children with neuroblastoma or sarcomas and adults with breast, colon or soft-tissue cancers, often respond poorly to standard chemotherapy. Certified tissue and blood tests could identify these patients and predict their outcomes. These tests could also serve as companion diagnostics to match them to drugs such as ATM inhibitors or p53 activators. The drug results could inform clinical trials that enroll patients by ALT status across many cancer types.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Matthew Waitkus
Duke University, NC·Medicine & Clinical Research
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.
Carl Gregory
Texas A&M University-College Station, TX·Medicine & Clinical Research
Measure how cDkkMo, a dog-specific antisense morpholino that blocks production of the Wnt-inhibitor protein Dkk-1, affects growth, survival and stress resistance of canine osteosarcoma cell lines and canine patient-derived xenografts.
Xinbin Chen
University of California-Davis, CA·Biochemistry
Determine how CDK4/6 enzymes, the RNA-binding protein RBM38 and the protein-synthesis factor eIF4G together boost mutant p53 production, and whether CDK4/6 inhibitors suppress triple-negative breast cancers partly by lowering mutant p53.
The school
Texas Tech University Health Sciences Center: 2 labs on PI Pages, $53M a year on research, 128 research doctorates a year.
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