MD
Distinguished Professor, Medicine-Gastroenterology
UNC-Chapel Hill
Immunology
Area of Interest
My research involves the study of EGFR family members, particularly their role in breast cancer pathogenesis and response to radiotherapy. One project investigates HER4. This relatively little-studied member of the EGFR family can mediate antiproliferative and differentiation effects in human breast cancer cells. In this context, HER4 may confer a favorable prognostic influence, and may be a tumor-suppressor target.
Another project investigates the effect of a newly developed EGFR/HER2 tyrosine kinase inhibitor. We have demonstrated that GW572016 represses tumor cell proliferation and radiosensitizes EGFR over-expressing breast cancer cells. Preclinical studies are underway and clinical radiosensitzation trials are being developed for recurrent breast cancer. We also have an ongoing clinical trial to determine the feasibility and efficacy of radiosensitizing locally advanced breast cancer using the HER2 inhibitor, Herceptin.
In order to better understand mechanisms of breast cancer radioresistance, we have developed a series of radioresistant breast cancer cell lines. A new project involves the establishment of human breast cancer xenografts in SCID mice, allowing us to develop new models of breast cancer radioresistance from radioresitant recurrent human tumors. We will use these xenografts to study mechanisms of radioresitance and novel radisosensitization approaches.
Finally, to better understand radiation responses in clinically relevant scenarios, we are studying the effect of a single dose of radiation on normal breast and tumor tissue, in the context of a single-dose intraoperative protocol. In this trial, patients with low-risk breast cancer are treated with a single dose of intraoperative radiotherapy to determine the feasibility of conveniently-delivered, partial breast radiotherapy.
