The research of John R. Hawse IV, Ph.D., focuses on two highly prevalent diseases: breast cancer and osteoporosis. Both of these diseases primarily affect women, and in many cases involve the functions of estrogen and estrogen receptors in mediating disease progression.
Dr. Hawse's group utilizes a wide variety of molecular biology and biochemistry techniques to address the roles of specific genes and treatment regimens in mediating the development, progression and therapeutic responsiveness of these diseases.
Dr. Hawse's research has been funded by the National Institutes of Health, Susan G. Komen for the Cure and Mayo Clinic.
Breast cancer. Dr. Hawse and his group are currently analyzing the anti-estrogenic properties of endoxifen, a tamoxifen metabolite.
Clinical studies have demonstrated that endoxifen concentrations are a key determinant for the efficacy of tamoxifen therapy, and Dr. Hawse's work has shown that the effects of endoxifen are different from those of other anti-estrogenic drugs and are primarily responsible for the beneficial outcomes observed in women receiving tamoxifen therapy.
Additionally, Dr. Hawse's group has begun to elucidate the expression patterns of a second estrogen receptor isoform, ERβ, in breast cancer. They have shown that a proportion of patients whose breast tumors are considered to be endocrine insensitive due to loss of ERα actually express ERβ.
This discovery opens the door for treating such patients with hormone-based therapies instead of chemotherapy. His ongoing work and future studies aim to further elucidate endoxifen's mechanism of action and determine the role of ERβ in mediating breast cancer progression and response to therapy.
Osteoporosis. Dr. Hawse's group is currently examining the role of TGFβ inducible early gene-1 (TIEG) in mediating the anabolic effects of estrogen in this tissue as well as its role in bone maintenance and turnover.
His team has demonstrated that loss of TIEG expression in mice results in an osteoporotic phenotype only in female mice, with no changes in bone strength, structure or microarchitecture observed in male animals.
More recently, they have implicated a critical role for TIEG in mediating the downstream effects of estrogen and Wnt signaling in bone. Future studies seek to determine the contribution of osteoblasts, osteoclasts and osteocytes in the gender-specific bone phenotype of TIEG knockout mice to further describe the actions of TIEG in bone.
Actions of endoxifen on the skeleton. A third project relating to both breast cancer and osteoporosis involves the actions of endoxifen on the skeleton. Currently, phase I trials examining the utility of endoxifen as a novel breast cancer therapy are ongoing at Mayo Clinic and the National Cancer Institute.
For these reasons, it is critical to define the potential side effects of this drug on other target tissues, including the skeleton. Interestingly, Dr. Hawse's team has demonstrated that endoxifen protects against bone loss following estrogen depletion in mice.
Ongoing studies seek to further elucidate the effects of endoxifen on bone and determine if endoxifen might serve as a novel therapeutic for the treatment of osteoporosis.
Significance to patient care
Dr. Hawse's research will aid in the understanding of the development and progression of breast cancer and osteoporosis. His group's efforts to identify and develop targeted drug therapies to treat both of these conditions have the potential to impact hundreds of thousands of women each year.