Memorial Hospital Research Laboratories
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.
Moore G, Majumdar R, Powell SN, Khan AJ, Weinhold N, Yin S, Higginson DS. Templated insertions are associated specifically with BRCA2 deficiency and overall survival in advanced ovarian cancer. Mol Cancer Res. 2022 Jul 6;20(7):1061-1070.
Hussain SS, Majumdar R, Moore GM, Narang H, Buechelmaier ES, Bazil MJ, Ravindran PT, Leeman JE, Li Y, Jalan M, Anderson KS, Farina A, Soni R, Mohibullah N, Hamzic E, Rong-Mullins X, Sifuentes C, Damerla RR, Viale A, Powell SN, Higginson DS. Measuring nonhomologous end-joining, homologous recombination and alternative end-joining simultaneously at an endogenous locus in any transfectable human cell. Nucleic Acids Res. 2021 Jul 21;49(13):e74.
Jonathan E Leeman, Yi Li, Andrew Bell, Suleman S Hussain, Rahul Majumdar, Xiaoqing Rong-Mullins, Pedro Blecua, Rama Damerla, Himanshi Narang, Pavithran T Ravindran, Nancy Y Lee, Nadeem Riaz, Simon N Powell, Daniel S Higginson. Human papillomavirus 16 promotes microhomology-mediated end-joining. Proc Natl Acad Sci USA. 2019 Oct 22; 116(43) 21573-21579.
Daniel S. Higginson, MD
- Physician-scientist Daniel Higginson studies a double-strand break repair pathway known as microhomology-mediated end joining, with the overall goal of improving the understanding of radiation treatment and providing insight into therapies for cancers deficient in homologous recombination.
- MD, Johns Hopkins University School of Medicine
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Daniel S. Higginson discloses the following relationships and financial interests:
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