Faculty Summaries
Neil Johnson, PhD
Neil Johnson, PhD
Member & Assistant Professor
neil.johnson@fccc.edu
Office Phone: 215-728-7016
Fax: 215-728-3616
Office: W446
  • Investigate determinants of homologous recombination proficiency in cancer cells
    Clinical mutations in the BRCA1 gene.
    Figure 1. Clinical mutations in the BRCA1 gene.

    Our current research suggests that a subgroup of tumors that contain mutations in essential DNA repair genes retain the ability to repair DNA and are consequently resistant to DNA damaging chemotherapies or PARP inhibitors. We are investigating factors that enable cancer cells that contain BRCA1 mutations to carry out homologous recombination DNA repair and survive chemotherapy. We are examining the ability of mutant BRCA1 proteins to contribute to homologous recombination in cancer cells. Moreover, we are investigating the influence of the cellular background on DNA damaging agent and PARP inhibitor sensitivity. We have recently screened the hORFeome V8.1 Expression Library generated by the Broad Institute (Harvard/MIT) to identify proteins that influence HR and PARP inhibitor sensitivity. The library is a genome-scale ORFeome collection in a lentiviral vector (16172 distinct ORFs mapping to 13833 genes). We aim to determine the potential of hits to serve as biomarkers for DNA damaging chemotherapy or PARP inhibitor sensitivity in patient tumors and determine whether they can serve as biomarkers for response in predictive clinical trials.

  • Investigate mechanisms of acquired resistance to DNA repair inhibitors
    The BRCA1 protein forms multiple protein complexes
    Figure 2. The BRCA1 protein forms multiple protein complexes.

    Despite substantial response rates of BRCA1 and BRCA2 mutant cancers to PARP inhibitor treatment, many patients fail to respond to treatment; additionally, patients that demonstrate initial responses ultimately acquire drug resistant tumors. We are interested in identifying mechanisms by which cancer cells adapt so that they can survive after treatment with DNA damaging agents or DNA repair inhibitors. We are utilizing PARP inhibitor-sensitive cancer cell lines to derive resistant sub-clones. Upon determining drug resistance mechanisms, we will examine PARP inhibitor or cisplatin sensitive and resistant human tumor biopsies for correlation to our preclinical data.

  • Identify small molecules that abrogate DNA repair pathways in cancer cells

    We are measuring the ability of compounds currently used in clinical studies or in preclinical development to abrogate DNA repair pathways. Additionally, we are screening small molecule libraries to identify novel compounds that block repair of DNA breaks. We will investigate the impact of the compounds on HR protein levels and ability to be recruited to sites of DNA damage by foci formation assays. Our goal is to develop novel compounds for in vivo use and eventual clinical applications.