V. Gustavo Blanco, M.D., PhD.
Kathleen M. Osborn Chair of Molecular & Integrative Physiology
Dept. of Molecular & Integrative Physiology
M.D., National University of Córdoba, Argentina, 1979-1985
Ph.D., Instituto de Investigación Médica Mercedes y Martin Ferreyra, Argentina, 1986-1990
Our laboratory studies the role of ion-transport proteins of the plasma membrane in cell function. Research is focused on the Na, K-ATPase, a plasma membrane enzyme system that uses the energy from ATP to establish and maintain the high internal K+ and low internal Na+ concentrations characteristic of most animal cells. The transporter comprises a group of isozymes, each characterized by unique enzymatic properties and a cell-dependent and developmentally regulated pattern of expression. We are interested in the function of alpha4, a particular isoform of the catalytic subunit of the Na,K-ATPase that is selectively expressed in spermatozoa. A variety of molecular and cellular biology methods are used to study the regulation, activity and mechanisms of action of alpha4, as well as the role of this Na,K-ATPase in the physiology of the male gametes. These studies will help understand the importance of ion transport in male germ cell fertility and contraception.
In addition, we are studying the role of the Na,K-ATPase in autosomal dominant polycystic kidney disease (ADPKD). We are currently investigating how ouabain affects cyst formation and progression in the disease.
Blanco G. Na,K-ATPase subunit heterogeneity as a mechanism for tissue-specific ion regulation. Sem. Nephrol. 25, 292-303 (2005).
Rodova M, Nguyen A-N and Blanco G. The transcription factor CREMt and cAMP regulate promoter activity of the Na,K-ATPase α4 isoform. Mol. Human Devel. 11:1435-47 (2006).
Nguyen A-N, Wallace DP, Blanco G. Ouabain Binds with High Affinity to the Na,K-ATPase in Human Polycystic Kidney Cells and Induces Extracellular Signal-Regulated Kinase Activation and Cell Proliferation. J Am Soc Nephrol. 18:46-57 (2007).
Wagoner K, Sanchez G, Nguyen A-N, Enders GC and Blanco G. Different expression and activity of the α1 and α4 isoforms of the NaK-ATPase during rat male germ cell ontogeny. Reproduction 130: 627-641 (2005).
Sanchez G., Nguyen A-N., Timmerberg B., Tash J.S. and Blanco G. The Na,K-ATPase α4 isoform from humans has distinct enzymatic properties and is important for sperm motility. Mol. Human. Reprod. 12:565-76 (2006).
Jimenez T, Sanchez G., Wertheimer E. and Blanco G (2010). Activity of the Na,K-ATPase alpha4 isoform is important for membrane potential, intracellular Ca2+, and pH to maintain motility in rat spermatozoa. Reproduction 139:835-45.
Jimenez T, Sanchez G, McDermott JP, Nguyen AN, Kumar TR, Blanco G. Increased Expression of the Na,K-ATPase alpha4 Isoform Enhances Sperm Motility in Transgenic Mice. Biol Reprod. 84: 153-61, 2010.
Jimenez T, McDermott JP, Sánchez G, Blanco G. Na,K-ATPase alpha4 isoform is essential for sperm fertility. Proc Natl Acad Sci U S A. 108:644-9, 2012.
Jimenez T, Sánchez G and Blanco G. Activity of the Na,K-ATPase alpha4 isoform is regulated during sperm capacitation to support sperm motility. J. Androl. 33(5):1047-57, 2012.
McDermott JP, Sánchez G, Chennathukuzhi V and Blanco G. Green fluorescence protein driven by the Na,K-ATPase alpha4 isoform promoter is expressed only in male germ cells of mouse testis. J. Assisted Reprod. Genet.. 29(12):1313-25, 2012.