Varki Tumor Glycomics Laboratory
Principal Investigator: Ajit Varki, M.D.
Institution: University of California, San Diego, CA
The Varki laboratory is focused on a family of sugar molecules called the sialic acids, and their roles in biology, evolution and disease.
The surfaces of all cells in all organisms are decorated with a dense and complex array of sugar chains. These glycans are known to mediate or modulate many biological processes including sub-cellular and cellular trafficking, intercellular adhesion, signaling, and microbial attachment. Much data also indicates their involvement in embryonic development, normal tissue organization, tumor metastasis, and in the interactions of cells with extra-cellular molecules.
Their Alliance project is based on the absence in humans of the enzyme to convert a common sialic acid, Neu5Ac, into Neu5Gc. Studies have found that ingested Neu5Gc, found in red meat and dairy products, incorporates into the sugar chains covering human cells. Cancer cells do this to a greater extent than normal cells. Additionally, all people develop some antibodies to these sugar chains containing foreign Neu5Gc. Using samples from the Moores UCSD Cancer Center Biorepository, with co-PI Richard Schwab they are testing the utility of measuring specific anti-Neu5Gc antibodies and urinary Neu5Gc levels for the early diagnosis of cancer.
Publications:
- Padler-Karavani V, Song X, Yu H, Hurtado-Ziola N, Huang S, Muthana S, Chokhawala HA, Cheng J, Verhagen A, Langereis MA, Kleene R, Schachner M, de Groot RJ, Lasanajak Y, Matsuda H, Schwab R, Chen X, Smith DF, Cummings RD, Varki A. Cross-comparison of protein recognition of sialic acid diversity on two novel sialoglycan microarrays. J Biol Chem. 2012; (In Press).
- Lu Q, Padler-Karavani V, Yu H, Chen X, Wu SL, Varki A, Hancock WS. LC-MS Analysis of Polyclonal Human Anti-Neu5Gc Xeno-Autoantibodies Immunoglobulin G Subclass and Partial Sequence Using Multistep Intravenous Immunoglobulin Affinity Purification and Multienzymatic Digestion. Anal Chem. 2012; (in press).
- SIGLEC12, a Human-specific Segregating (Pseudo)gene, Encodes a Signaling Molecule Expressed in Prostate Carcinomas. Mitra N, Banda K, Altheide TK, Schaffer L, Johnson-Pais TL, Beuten J, Leach RJ, Angata T, Varki N, Varki A. J Biol Chem. 2011; 286:23003-11.
- Human xeno-autoantibodies against a non-human sialic acid serve as novel serum biomarkers and immunotherapeutics in cancer. Cancer Res. 2011; 71:3352-3363
- Padler-Karavani V, Varki A. Potential impact of the non-human sialic acid N-Glycolylneuraminic acid on transplant rejection risk. Xenotransplantation (Invited Commentary), 2011; 18:1-5.
- Taylor RE, Gregg CJ, Padler-Karavani V, Ghaderi D, Yu H, Huang S, Sorenson RU, Chen X, Inostroza J, Nizet V, Varki A. Novel mechanism for the generation of human xeno-autoantibodies against the nonhuman sialic acid N-glycolylneuraminic acid. J. Exp. Med. 2010; 207:1637-1646.
- Chen X, Varki A. Advances in the biology and chemistry of sialic acids. ACS Chem Biol. 2010;5(2):163-76.
- Diaz SL, Padler-Karavani V, Ghaderi D, Hurtado-Ziola N, Yu H, Brinkman-Van der Linden ECM, Varki A, Varki N.M. Sensitive and specific detection of the non-human sialic acid n-glycolylneuraminic acid in human tissues and biotherapeutic products. PLoS ONE. 2009;4(1):e4241.
- Padler-Karavani V, Yu H, Cao H, Chokhawala H, Karp F, Varki N, Chen X, Varki A. Diversity in specificity, abundance and composition of anti-Neu5Gc antibodies in normal humans: potential implications for disease. Glycobiology. 2008;18:818-830.
- Hedlund M, Padler-Karavani V, Varki N, Varki A. Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression. Proc. Natl. Acad. Sci. U.S.A. 2008;105:18936-18941.
In the Media:
"Science Focus: Ajit Varki" Nick Zagorski, American Society for Biochemistry and Molecular Biology (ASBMB), December 2010
"Ajit Varki: On the origins of maladies," Amy Maxmen, Journal of Experimental Medicine, 2009;206 1836-1837. Published online August 31, 2009.
"How Eating Red Meat Can Spur Cancer Progression," Debra Kain, UCS San Diego News Center, online. November 13, 2008.
"Award to UCSD to Fund Novel Approaches to Detecting Cancer," Debra Kain, UCS San Diego News Center, online. October 8, 2007.
Patents
Provisional application: Compositions and Methods for Detecting Cancer. Filed: January 14, 2011 (serial# 13/007237).
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