My research focuses on how cells respond to stresses such as heat and radiation. My laboratory was one of the first to demonstrate the role of heat shock protein 70 (Hsp70) in permanent heat resistance and in transient thermal tolerance in mammalian cells. In studying heat shock regulation and DNA damage repair, we were also one of the first groups to establish a full complement of knockout mice of the DNA-PK repair complex: Ku70, Ku80, and DNA-PKcs. Recognizing the opportunity to target the DNA repair process for enhancing radiation response, we developed a gene therapy approach using molecular vectors of anti-Ku70 and dominant negative Ku70, demonstrating that delivering antisense Ku70 into the tumor enhances the response to radiation treatment.
Given the negative impact of tumor hypoxia on cancer radiotherapy and the expertise at Memorial Sloan-Kettering for imaging tumor hypoxia, we have further refined our gene therapy strategy to use hypoxia image guidance to target the most radio-resistant cells in the tumor.
Currently, my laboratory is using a novel tumor model to study hypoxia-induced global transcriptional response and investigating the application of the in vivo hypoxia gene signature as a prognostic tool for treatment outcome of cancer therapy.