Thomas L McCarthy PhD
Departments & OrganizationsMacMillan Center
Yale Core Center for Musculoskeletal Disorders
Surgery: Plastic & Reconstructive Surgery
BiographyMy laboratory in collaboration with Dr. Centrella is interested in the expression and control of IGF-I and TGF-beta activity by osteoblasts. Using molecular dissection of promoters we have discovered key cis- and trans-acting regulatory elements that control IGF-I expression, as well as the three key types of TGF-beta receptors. Additional studies examine the influence of steroid hormones on growth factor expression and activity, and these include studies that examine how steroid hormones interact with protein kinase mediated gene activation. Sex steroids play a critical role in the maintenance of skeletal integrity, and we have found that they function as co-modulators of kinase mediated regulation of growth factor expression or activity.
Our recent studies demonstrate that osteoblasts are able to alter native and synthetic sex steroid structure and therefore activity through the expression of endogenous oxidative and reductive enzymes. We recently published a surprising discovery that aging osteoblast cultures produce and release a potent selective estrogen receptor modulator, and we are currently in the process of identifying its molecular structure. Together with Dr. Centrella we are also studying Wnt pathway activation by growth factors and steroid hormones. Our goal is to understand regulators of osteoblast activity so that we and others may apply our findings to the development of potential therapeutics to enhance skeletal healing in patients and to improve skeletal integrity in our ever accumulating aging population.