Laura Wright, Ph.D.
980 W. Walnut St.
Walther Hall R3 Room C122
Indianapolis, IN 46202
Phone: (317) 278-7785
Fax: (317) 278-2912
Research Program Membership
Assistant Research Professor of Medicine
Department of Medicine
Division of Endocrinology
IU School of Medicine
Current research objectives 1) Determine the effects of radiation therapy on bone and cancer progression in the skeleton. Patients undergoing radiation therapy for cancer are at increased risk of musculoskeletal complications including bone loss and fracture. An overarching goal of my work is to evaluate the cellular mechanism(s) of radiation-induced bone loss and to determine the effects of radiation exposure on the development and progression of prostate cancer bone metastases. My findings indicate that radiation exposure can have direct effects on multiple bone cells (osteoclasts, osteoblasts and osteocytes) and that radiation-induced bone loss may be partially driven by systemic factors, including osteoclastogenic cytokines. Further studies are underway to determine the relative contribution of inflammatory cytokines on short- and long-term radiation-induced bone loss, as well as the role that radiation-induced bone loss may play in the progression of cancer bone metastases. These studies emphasize the sensitivity of the musculoskeletal system to radiation, and may be useful in developing therapeutics that can prevent musculoskeletal weakness in cancer patients following radiation exposure. 2) Prevent life-threatening osteolytic breast cancer bone metastases in cancer patients. Of women with advanced breast cancer, it is estimated that up to 80% will present with clinically evident bone metastases for which there is currently no cure. My preclinical work is focused on evaluating the relative effects of two widely used anti-E2 therapies (aromatase inhibitors and selective estrogen receptor modulators) on bone loss and the progression of breast cancer bone metastases. Information obtained from my studies could help guide the selection of adjuvant therapeutics for breast cancer patients and survivors, with emphasis on the importance of maintaining bone in order to prevent cancer recurrence, cancer cell homing to sites in the skeleton, and/or muscle weakness associated with anti-E2 therapeutics. Understanding the role that high bone turnover plays in facilitating cancer metastasis to distant sites could also have applications for other types of breast cancer therapeutics that are known to have adverse effects on bone (e.g., radiation therapy, glucocorticoids). 3) Improve muscle function and endocrine therapy compliance in cancer patients. Adjuvant hormone therapies are associated with muscle weakness and joint pain in cancer patients. The mechanism(s) of androgen and estrogen deprivation-induced muscle dysfunction have not been identified, although sex steroid deficiency is associated with increased inflammation and oxidative stress. The ryanodine receptor (RyR1), a calcium release channel on the sarcoplasmic reticulum, is required for muscle excitation-contraction coupling. Pathological oxidation-dependent depletion of the stabilizing subunit calstabin from RyR1 results in leaky channels and impaired muscle function. I am currently evaluating the effects of sex steroid deprivation on RyR1-calstabin stability and skeletal muscle contractility. My aim is to determine whether pharmacological stabilization of the RyR1 channel might ameliorate muscle weakness in breast and prostate cancer patients treated with adjuvant hormone therapy. Long-term research and career objectives Beyond the completion of my Department of Defense Breast Cancer Award, I hope to continue to elucidate the short- and long-term effects of cancer therapies on the musculoskeletal system and tumor microenvironment. In the future, I am interested in pursuing the role of obesity and bone marrow adipose tissue on breast and prostate cancer metastases.
Post-doctoral Fellowship - Indiana University, Indianapolis, IN 2015
Ph.D. - University of Arizona, Tucson, AZ 2012
M.S. - University of Arizona, Tucson, AZ 2007