Comparative study of sialic acids in humans and chimpanzees

Pascal Gagneux

Appointment Period: 1998-1999 / Grant Year: [14]

My research project investigated transgenic manipulation of tissue-specific sialylation in mice, by producing transgenic mice that express an enzyme responsible for placing sialic acid in a specific linkage on their lung epithelial cells (alpha 2-6 to underlying galactose). These mice will be a model for human adapted influenza A virus that preferentially binds alpha 2-6- linked sialic acid.

PUBLICATIONS (resulting from this training, and some recent ones)

Gagneux P, Varki A. (1999) Evolutionary considerations in relating oligosaccharide diversity to biological function. Glycobiology 9:747-55.

Gagneux P, Amess B, Diaz S, Moore S, Patel T, Dillmann W, Parekh R, Varki A. (2001) Proteomic comparison of human and great ape blood plasma reveals conserved glycosylation and differences in thyroid hormone metabolism. Am J Phys Anthropol 115:99-109.

Hayakawa T, Satta Y, Gagneux P, Varki A, Takahata N. (2001) Alu-mediated inactivation of the human CMP- N-acetylneuraminic acid hydroxylase gene. Proc Natl Acad Sci USA 98:11399-404

Tangvoranuntakul P, Gagneux P, Diaz S, Bardor M, Varki N, Varki A,Muchmore E. (2003) Human uptake and incorporation of an immunogenicnonhuman dietary sialic acid. Proc Natl Acad Sci U S A. 100:12045-50.

Gagneux P, Cheriyan M, Hurtado-Ziola N, van der Linden EC, Anderson D, McClure H, Varki A, Varki NM. (2003) Human-specific regulation of alpha 2-6-linked sialic acids. J Biol Chem 278:48245-50.

Martin MJ, Rayner JC, Gagneux P, Barnwell JW, Varki A. (2005) Evolution of human-chimpanzee differences in malaria susceptibility: relationship to human genetic loss of N-glycolylneuraminic acid. Proc Natl Acad Sci U S A. 102:12819-24.

Nguyen DH, Hurtado-Ziola N, Gagneux P, Varki A. (2006) Loss of Siglec expression on T lymphocytes during human evolution. Proc Natl Acad Sci U S A. 103:7765-70.