Clifford W. Mason, Ph.D.
Department of Obstetrics and Gynecology
Ph.D., University of Maryland School of Pharmacy, 2008
Postdoctoral, University of Maryland, 2008-2009
Postdoctoral, University of Kansas Medical Center, 2009-2010
Regulation of Drug Transport
The core of this research focuses on the pathopharmacology of the maternal-placental-fetal unit. Intrauterine infection is a major threat to mother and baby. It is associated with more than 50% of women who deliver prematurely and is implicated in fetal / neonatal neurological and respiratory damage. Our data indicate there are changes in drug transport proteins in placenta of women with infection and associated chorioamnionitis. Changes in placental transporters could result in altered fetal drug exposure leading to therapeutic insufficiency or drug toxicity. Our research addresses three core questions. First, how do pathophysiological responses to infection affect placental drug transporters? Second, do pathological changes in transporter expression levels correlate with placental drug transfer, and therapeutic outcome? Finally, what are the regulatory pathways that drive transporter expression and can pharmacoresistance to drugs be overcome by targeted inhibition of proteins within these pathways? The results will help predict how pathophysiological responses to infection during pregnancy alter placental transfer and therapeutic efficacy of drugs.
Mechanisms of Smooth Muscle Contractility
Changes in intracellular calcium and its relationship with contractile proteins within the myometrium have important functional consequences as they determine contractility and its regulation. Much of calcium signaling is mediated through calmodulin. There exist a number of endogenous proteins that help regulate calcium-calmodulin dependent processes through their interaction with calmodulin. Our interest lies in the functional expression of these calmodulin-binding proteins in myometrium during pregnancy. We believe that changes in their expression in smooth muscle cells could contribute to altered contractility and thus abnormal labor. We use a various molecular biology and cellular imaging techniques in both immortalized and human primary myometrial smooth muscle cells to delineate the function of these proteins and their implications in abnormal contractility.
Mason CW, Buhimschi IA, Buhimschi C, Dong Y, Weiner CP, Swaan PW. ABC placental transporter expression as a function of pregnancy condition. Drug Metabolism and Disposition 2011;39:1000-7.
Weiner CP, Mason CW, Dong Y, Buhimschi IA, Swaan PW, Buhimschi C. Human effector / initiator gene sets that regulate myometrial contractility during term and preterm labor. American Journal of Obstetrics and Gynecology 2010;202:474 e471-420.
Coowanitwong I, Keay SK, Natarajan K, Garimella TS, Mason CW, Grkovic D, Bauer KS. Toxicokinetic study of recombinant human heparin-binding epidermal growth factor-like growth factor (rhHB-EGF) in female sprague dawley rats. Pharmaceutical Research 2008;25:542-550.
Mason CW, Swaan PW, Weiner CP. Identification of interactive gene networks: A novel approach in gene array profiling of myometrial events during pregnancy. American Journal of Obstetrics and Gynecology 2006;194:1513-23.
Mason CW, D'Souza VM, Bareford LM, Phelp MA, Ray A, Swaan PW. Recognition, cointernalization and recycling of an avian riboflavin carrier protein in human placental trophoblasts. Journal of Pharmacology and Experimental Therapeutics 2006;317:465-72.
Weiner CP, Mason CW, Hall G, Ahmad U, Swaan PW, Buhimschi IA. Pregnancy and estradiol modulate myometrial g-protein pathways in the guinea pig. American Journal of Obstetrics and Gynecology 2006;95:275-87.