Research
Our research interests include DNA repair, cancer therapy, tumor hypoxia, and gene editing for gene therapy.
DNA Repair: Novel pathways that regulate the DNA damage response.
We have discovered that the oncometabolite, 2-hydroxyglutarate, generated by neomorphic IDH mutations in gliomas and other malignancies suppresses homologous recombination and confers PARP inhibitor sensitivity, identifying a new approach to treat these malignancies.
Cancer Therapy: Novel DNA repair inhibitors
There has been a surge of interest in DNA repair pathways as potential targets for cancer therapy strategies, not only to potentiate existing cancer therapies such as radiation and DNA damaging chemotherapy but also to take advantage of the frequent DNA repair abnormalities in human cancer cells to achieve synthetic lethality and consequent therapeutic gain.
Hypoxia: Impact on genetic instability, DNA repair, gene silencing, and therapeutic resistance.
We hypothesized that that acquired genetic instability in cancer cells may arise from the dysregulation of critical DNA repair pathways due to cell stresses within the tumor microenvironment such as hypoxia.
Gene editing: Triplex DNA provokes DNA repair and stimulates site-specific gene editing.
From an interest in studying cellular DNA repair and recombination pathways, we recognized the utility of DNA triple helix formation as a mechanism for the site-specific introduction of DNA damage in mammalian cells.
Links to Protocols
Strain Information
Strains: BHB2688 and NM759
Contact: Denise Hegan
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Research Funding
- NIH: R35 CA197574. Novel DNA Repair Inhibitors for Cancer Therapy
- NIH: R01 ES005775. Hypoxia, DNA Repair, and Gene Silencing
- NIH: UG3 HL147352. Poly(amine-co-ester)s for Targeted Delivery In Vivo of Gene Editing Agents to Bone Marrow and Lung
- NIH: R01 HL139756. Nonenzymatic Gene Editing in Treatment of Heredity Spherocytosis
- NIH: U01 AI145965. PNA Nanoparticles for Gene Editing In Vivo
- Cystic Fibrosis Foundation. Collaborative Research Grant. Targeted Correction of W1282X-CFTR