Barry R. Rosen, Ph.D.

The goals of the Rosen laboratory are to elucidate the molecular mechanisms of heavy metal detoxification and homeostasis, in particular As(III), Sb(III), Cd(II), Pb(II), Zn(II), Cu(I) and Ag(I). Our approaches span the gamut of science from cell and molecular biology and genetics to biochemistry and biophysics to structural biology, and students have the opportunity to gain experience in most methods in modern biology. We have elucidated the pathways of arsenic detoxification in bacteria, yeast, Leishmania, plants and animals. We identified the first Zn(II) ATPase, which is responsible for zinc homeostasis in E. coli and the Cu(I) ATPase that is the best model system for Menkes and Wilson Diseases. We showed first that aquaglyceroporins are the major route of uptake of arsenite in mammals, which is medically relevant since arsenite is the active ingredient of the anti-leukemia drug Trisenox. Arsenic is a major environmental pollutant in many parts of the world, causing neurological disease and cancer. We have bioengineered yeast for bioremediation of arsenic in drinking water and transgenic plants for phyotremediation of arsenic from soil. Using transcriptional reporter assays we have constructed biosensors for environmental arsenic, cadmium and lead. At the molecular level we have cloned the genes and purified the proteins for these systems and determined the mechanisms of genetic regulation. We have characterized many of these proteins biophysically using methods such as fluorescent spectroscopy and have solved their structure by x-ray crystallography and nuclear magnetic resonance. Graduates of our lab have gone on to successful careers in academics and industry.

Liu, Z., Carbrey, J.M., Agre, P. and Rosen, B.P. Arsenic trioxide uptake by human and rat aquaglyceroporins. Biochem. Biophys. Res. Commun. 316, 1178-1185 (2004).

Ramírez-Solís, A., Mukopadhyay, R., Rosen, B.P. and Stemmler, T.L. Experimental and theoretical characterization of arsenite in water: Insights into the coordination environment of As-O. Inorg Chem. 43, 2954-2959 (2004).

Liu, Z., Boles, E. and Rosen, B.P. Arsenic trioxide accumulation by hexose permeases in Saccharomyces cerevisiae. J. Biol. Chem. 279, 17312-17318 (2004).

Li, P., Uddin, A.N., Liu, Z., Mukhopadhyay, R., Komissarova, E.V., Rosen, B.P. and Rossman, T.G. Variability in sensitivity to arsenite does not correlate with arsenic accumulation rate in normal human lymphoblasts. Mol. Cell. Biochem. 255, 79-85 (2004).

Meng, Y., Liu, Z. and Rosen, B.P. As(III) and Sb(III) uptake and efflux in Escherichia coli. J. Biol. Chem. 279, 18334-18341 (2004).

DeMel, S., Shi, J., Martin, P., Rosen, B.P. and Edwards, B.F.P. Contribution of arginine 60 to the mechanism of E. coli ArsC arsenate reductase (R773). Prot. Sci., 13, 2330-2340 (2004).

Gourbal, B., Sonuc, N., Bhattacharjee, H., Legare, D., Sundar, S., Ouellette, M., Rosen, B.P. and Mukhopadhyay, R., Drug uptake and modulation of drug resistance in Leishmania by an aquaglyceroporin. J. Biol. Chem. 279, 31010-31017(2004).

Bhattacharjee, H., Carbrey, J., Rosen, B.P. and Mukhopadhyay, R., Drug uptake and modulation of drug sensitivity in leukemia by AQP9. Biochem. Biophys. Res. Commun. 322, 836-841(2004).

Zhou, Y., Messier, N., Ouellette, M, Rosen, B.P. and Mukhopadhyay, R., Leishmania major LmACR2 is a pentavalent antimony reductase that confers sensitivity to the drug Pentostam. J. Biol. Chem. 279, 37445-37451 (2004).

Jiang, Y., Bhattacharjee, H., Zhou, T., Rosen, B.P., Ambudkar, S.V. and Sauna, Z.E. Nonequivalence of the nucleotide binding domains of the ArsA ATPase. J. Biol. Chem. 280,9921-9926 (2005).

Ye, J., Kandegedara, A., Martin, P. and Rosen, B.P. Structure of the Staphylococcus aureus pI258 CadC Cd(II)/Pb(II)/Zn(II)-responsive repressor. J Bacteriol. 187,4214-4221 (2005).

Yang, H.C., Cheng, J., Finan, T.M., Rosen, B.P. and Bhattacharjee, H. A novel pathway for arsenic detoxification in the legume symbiont Sinorhizobium meliloti. J. Bacteriol. 187, 6991-6997 (2005).

Marquis, N., Gourbal, B., Rosen, B.P., Mukhopadhyay, R. and Ouellette M. Modulation in aquaglyceroporin AQP1 gene expression in drug resistant Leishmania. Mol. Microbiol. 57, 1690-1699 (2005).