The Daniel Higginson Lab

The Higginson lab focuses on alternative DNA double strand break repair pathways that become particularly important in tumors deficient in homologous recombination (e.g. BRCA1 or BRCA2 mutant tumors) and in tumors relatively deficient in non-homologous end-joining (e.g. HPV-associated tumors). These alternative pathways include alternative end-joining and single strand annealing. We employ advanced genome editing approaches to measure the full spectrum of repair events at a double strand break to quantify the use of both standard and alternative repair pathways. This approach allows for study of pathway tradeoffs that occur in the context of cancer-specific genetic alterations or when DNA damage response inhibitors (DDRi) are used. We seek to understand these pathways better in order to improve the therapeutic response to radiation and other DNA-damaging agents by finding rational combinations of DDRi to use in combination with radiation and matched to tumor-specific repair deficiencies.

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