Professor

Academic Degrees

• MD

Departmental Affiliation

• Name:

  Molecular Microbiology and Immunology

  Affiliation Type:

  Primary

Center and Institute Affiliations

• Information Projects Malaria Research Institute

Departmental Address

Contact Information

Email:

pagre@jhsph.edu

Phone:

443-287-8745

Fax:

410-955-0105

Research and Professional Experience

Aquaglyceroporins in malaria During the rapid growth of malarial parasites within red blood cells, glycerol is taken up by the parasites and incorporated into lipids for membrane biosynthesis. In order for the parasite to have access to glycerol, it must cross the red blood cell plasma membrane and the parasitic plasma membrane. We have shown that aquaglyceroporins are expressed in both membranes in mice. Aquaporin 9 (AQP9) is expressed in the red blood cell plasma membrane and Plasmodium berghei aquaglyceroporin (PbAQP) is expressed in the parasite plasma membrane. We have recently shown that PbAQP null malarial parasites grow more slowly in mice. As a result, mice infected with PbAQP null parasites survive longer than mice infected with wild type parasites. In addition, mice that are deficient in AQP9 survive longer during the initial portion of malarial infection compared to wild type mice. This suggests that aquaglyceroporins are important during malarial infection. Further studies will examine the role of aquaglyceroporins in other stages of the malarial parasite life cycle and their role in the human malarial parasite, Plasmodium falciparum.

Honors and Awards

2000 National Academy of Sciences 2003 Nobel Prize in Chemistry

Selected Publications

Liu Y, Promeneur D, Rojek A, Kumar N, Frokiaer J, Nielsen S, King LS, Agre P, and Carbrey JM. 2007. Aquaglyceroporin AQP9: The major pathway for glycerol uptake by mouse erythrocytes with implications for malarial virulence. Proc Natl Acad Sci USA 104:12560-4.

Promeneur D, Liu Y, Maciel J, Agre, King LS, and Kumar N. 2007. Aquaglyceroporin PbAQP during intraerythrocytic development of the malaria parasite Plasmodium berghei. Proc Natl Acad Sci USA 104: 2211-16.

Rojek A, Skowronski MT, Fuchtbauer EM, Fuchtbauer AC, Fenton RA, Agre P, Frokiaer J, and Nielsen S. 2007. Defective glycerol metabolism in aquaporin 9 (AQP9) knockout mice. Proc Natl Acad Sci USA 104: 3609-14.

Huang CG, Lamitina T, Agre P, and Strange K. 2007. Functional analysis of the aquaporin gene family in C. elegans. Am J Physiol Cell Physiol 292: C1867-73.

Saparov SM, Liu K, Agre P, and Pohl. 2006. Fast and selective ammonia transport by aquaporin-8. J Biol Chem 282: 5296-5301.

Lee KJ, Kozono D, Remis J, Kitagawa Y, Agre P, and Stroud RM. 2005. Structural basis for conductance by the archael aquaporin AqpM at 1.68 Å. Proc Natl Acad Sci USA 102: 18932-18937.

Liu K, Kozono D, Kato Y, Agre P, Hazama A, and Yasui M. 2005. Conversion of aquaporin-6 from an anion channel to a water-selective channel by a single amino acid substitution. Proc Natl Acad Sci USA 102: 2192-2197.

Liu K, Nagase H, Huang CG, Calamita G, and Agre P. 2005. Purification and functional characterization of Aquaporin-8. Biol Cell 98: 153-161.

Beitz E, Liu K, Ikeda M, Guggino WB, Agre P, and Yasui M. 2005. Determinants of AQP6 trafficking to intracellular sites vs. to the plasma membrane in transfected mammalian cells. Biol Cell 98: 101-109.

Furman CS, Gorelick-Feldman DA, Davidson KGV, Yasumura T, Neely JD, Agre P, and Rash JE. 2003. Aquaporin-4 square array assembly: Opposing actions of M1 and M23. Proc Natl Acad Sci USA 100: 13609-13614.

Kozono D, Ding X, Iwasaki I, Meng X, Kamagata Y, Agre P, and Kitagawa Y. 2003. Functional expression and characterization of an archael aquaporin, AqpM from Methanothermobacter marburgensis. J Biol Chem 278: 10649-10656.

Carbrey JM, Gorelick-Feldman DA, Kozono D, Praetorius J, Nielsen S, and Agre P. 2003. Aquaglyceroporin AQP9: Solute permeation and metabolic control of expression in liver. Proc Natl Acad Sci USA 100: 2945-2950. Liu Z, Shen J, Carbrey JM, Mukhopadhyay R, Agre P, and Rosen BP. 2002. Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9. Proc Natl Acad Sci USA 99: 6053-6058.

Hazama A, Kozono D, Guggino WB, Agre P, and Yasui M. 2002. Ion permeation of AQP6 water channel protein: Single-channel recordings after Hg2+ activation. J Biol Chem 277: 29224-29230.

Ikeda M, Beitz E, Kozono D, Guggino WB, Agre P, and Yasui M. 2002. Characterization of aquaporin-6 as a nitrate channel in mammalian cells: Requirement of pore-lining residue threonine-63. J Biol Chem 277: 39873-39879.

Neely JD, Amiry-Moghadam M, Ottersen OP, Froehner SC, Agre P, and Adams ME. 2001. Syntrophin-dependent expression and localization of Aquaporin-4 water channel protein. Proc Natl Acad Sci USA 98: 14108-14113.