Description of Research Expertise
My laboratory is attempting to better understand the molecular physiology of human blood flukes such as Schistosoma mansoni. Schistosomes are parasitic flatworms that cause schistosomiasis. Approximately one sixth of the world's population is at risk for this disease, and hundreds of millions of people worldwide are infected with these parasites. The lab focuses on two major projects: the role of schistosome multidrug resistance proteins in parasite physiology, and the interaction of these transporters with praziquantel, the drug of choice against schistosomiasis; and the structure and function of schistosome voltage-gated Ca2+ (Cav) channels, and their role in praziquantel action. The tools we use include molecular biology, RNA interference, electrophysiology, heterologous expression, behavioral assays, and flow cytometry. Other projects focus on mechanisms by which schistosomiasis-associated anemia might develop, the role of nitric oxide (NO) signaling systems in schistosomes, and the structure, function, and pharmacological sensitivities of various schistosome channels and receptors.
Kasinathan, R.S., and Greenberg, R.M Pharmacology and potential physiological significance of schistosome multidrug resistance transporters Exp. Parasitol. 132: 2-6, 2012.Kasinathan, R., Goronga, T., Messerli, S.M., Webb, T.R., and Greenberg, R.M. Modulation of a Schistosoma mansoni multidrug transporter by the antischistosomal drug praziquantel. FASEB Journal 173: 25-31, 2010.Kasinathan RS, Morgan WM, Greenberg RM. Schistosoma mansoni express higher levels of multidrug resistance-associated protein 1 (SmMRP1) in juvenile worms and in response to praziquantel. Mol Biochem Parasitol 173: 25-31, 2010.Salvador-Recatalà V, Greenberg RM The N terminus of a schistosome beta subunit regulates inactivation and current density of a Cav2 channel. J. Biol. Chemistry 285: 35878-35888, 2010.Kasinathan RS, Greenberg RM Schistosoma mansoni soluble egg antigens trigger erythrocyte cell death. Cell Physiol Biochem 26: 767-774, 2010.Messerli SM, Kasinathan RS, Morgan W, Spranger S, Greenberg RM Schistosoma mansoni P-glycoprotein levels increase in response to praziquantel exposure and correlate with reduced praziquantel susceptibility. Mol Biochem Parasitol. 167: 54-59, 2009.Salvador-Recatala, V., Schneider, T., and Greenberg, R.M. Atypical properties of conventional and variant Ca2+ channel Beta subunits from Schistosoma mansoni. BMC Physiology 8: 6, 2008.Greenberg, R.M. Molecular target of the antischistosomal drug praziquantel. Future Microbiology 2: 265-268, 2007.Messerli, S.M., Birkeland, S.R., Bernier, J., Cipriano, M.J., Morgan, W., McArthur, A.G., and Greenberg, R.M. Nitric oxide-dependent changes in Schistosoma mansoni gene expression. Mol. Biochem. Parasitol 150: 367-370, 2006.