Pascal Gagneux

Associate Professor

Pascal Gagneux got his MS in population biology and his PhD on the population genetics of West African chimpanzees from Basel University, Switzerland. Dr. Gagneux did a Post-Doc with Dr. Ajit Varki at University of California San Diego, studying sialic acid biology and disease susceptibility in humans and chimpanzees. In 2003, Dr. Gagneux joined Dr. Alan Dixson’s group and worked on primate reproductive biology as a research scientist at the San Diego Zoo’s Center for Reproduction of Endangered Species. In 2007, Dr Gagneux joined the faculty of Cellular and Molecular Medicine at UC San Diego. Since 2008, Dr. Gagneux is Associate Director of the Center of Academic Research and Training in Anthropogeny (CARTA), an Organized Research Unit at UC San Diego. In that capacity, Dr. Gagneux also runs the Graduate Specialization in Anthropogeny, a unique transdisciplinary graduate specialization for PhD students from eight UC San Diego graduate program.  Dr. Gagneux brings his expertise in evolutionary biology, primatology and glycobiology to the Division of Comparative Pathology and Medicine of the Pathology Department at UC San Diego.


Education

Post Doc in Glycobiology Research and Training Center, University of California San Diego

Ph.D in Zoology, Basel University, Basel, Switzerland

MS in Population Biology, Basel University, Basel, Switzerland

The Gagneux lab studies the roles of glycans in reproduction and infection. Glycans are diverse and variable saccharide chains attached to proteins and lipids. Glycans can differ by species, individual, cell type, and even physiological state or developmental stage. Glycan variation influences many phenotypes: from cellular recognition during fertilization and development, to infection, immunity, and cancer. So far, we know little about the evolutionary forces that shape glycan variation. This is an important gap in our knowledge, because glycans are central to cellular recognition, and to human health and disease. 

As a paradigm of cellular recognition, we study how mammalian sperm interact with the female reproductive tract. In mammals, fertilization is internal and requires that sperm survive inside the female until they reach the egg. We aim to understand how sperm interact with the female and her immune system via their surface glycans. Our laboratory discovered the presence of neuraminidases (sialidases) on mammalian sperm and found their activity to be critical for sperm capacitation and fertilization. Studying how glycans promote female tolerance and allow fertilization promises new understanding of cellular recognition mechanisms and the molecular basis of reproductive incompatibility. Pathogens exploit glycans to gain entry into host cells. This conflict, and the measures that evolve in response, are visible in the diversity of host and pathogen glycan phenotypes. Viruses and bacteria often use glycan-binding proteins to recognize and attach to host tissues. In return, hosts cover their external surfaces with secreted mucins that can act as protective decoys. We documented how influenza A viruses use their neuraminidase during ingress to cleave sialic acid receptors from host decoy molecules (mucins) and we showed that neuramindase inhibitors potentiate the protective effect of sialic acid rich host mucins.

Glycans on microbes can be targeted by the host using an array of innate immune system lectins. Many microbes evolve surface glycans that mimic the form of host glycans to hide from host immune responses. The diversity and rapid evolution of glycans is likely an outcome of synergistic and antagonistic interactions during reproduction and infection. 

Ghaderi, D., Springer, S., Ma, F., Cohen, M., Secrest, P. ,Taylor, R., Varki, A., and Gagneux, P. 2011. Sexual selection by female immunity against paternal antigens can fix loss of function alleles. Proc. Natl. Acad. Sci. USA. 108(43):17743-8.

O’Bleness, M., Searles, V., Varki, A., Gagneux, P. and Sikela, J. 2012. Genetic and Genomic Features Unique to the Human Lineage. Nature Reviews Genetics 13, 853-866.

Ma, F., Wu, D., Deng, L., Secrest, P., Zhao, J., Varki, N., Lindheim, S and Gagneux, P. 2012 Sialidases on Mammalian Sperm Mediate Deciduous Sialylation During Capacitation. J Biol Chem. 287:38073-9.

Cohen M., Zhang XQ., Senaati HP., Chen HW., Varki N. Schooley, RT., Gagneux P. 2013. Influenza A penetrates host mucus by cleaving sialic acids with neuraminidase. Virology Journal 10:321.

Springer, A.S. and Gagneux. P. 2013 Glycan Evolution in Response to Collaboration, Conflict, and Constraint J Biol Chem. 288(10):6904-11.

Springer, S. Diaz, S., Gagneux, P. Independent Inactivation of Cmah and Loss of Neu5Gc in New World Primates. 2014.  Immunogenetics. Epub. Aug 16 Epub head of print.