Birgit Zipser, Ph.D.
Our research interest focuses on the biological role of neutral glycosylations in ontogeny, phylogeny and tumorigenesis.
I. This interest originated from our early monoclonal antibody work on a neurobiological model, the leech (Zipser and McKay, 1981) - featured in Life Illuminated, Selected papers from Cold Spring Harbor, Volume 2, 1972-1994. In leech, different cell-type-specific glycosylations of an adhesion molecule belonging to the L1CAM immunoglobulin superfamily regulate sequential steps in synaptogenesis (reviewed in Tai and Zipser, 2002). The glycoepitope mediating axonal sprouting was isolated and structurally characterized as a beta-(1,4)-linked mannopyranose polymer (Huang, Hollingsworth, Haslam, Morris, Dell and Zipser, 2008). In Caenorhabditis elegans, the foremost invertebrate model systems for glycomic analysis, this Lan3-2 glycoepitope is also expressed cell-type-specifically on a L1CAM homologue. (VanSteenhouse, Horton, O’Hagan, Tai and Zipser, 2010) .
II. Isolating neutal glycans from human brain, demonstrated that brains afflicted with Alzheimer Disease accumulate amylose, the unbranched alpha-(1,4)-linked glucose polymer that is resistant to degradation by glycolytic enzymes (Huang, Hollingsworth, Castellani and Zipser, 2004). A synthesis of amylose at the expense of glycogen compromises glucose metabolism and enhances neural degeneration.
III. Currently, we are developing our unique monoclonal antibody, termed Mannitou, as a potential probe for a cancer-driven glyco-biomarker and as a candidate therapeutic reagent against cancer ( Zipser B, Bello-DeOcampo D, Diestel S, Tai MH, Schmitz B, 2012).
Mannitou Monoclonal Antibody Uniquely Recognizes Paucimannose, a Marker for Human Cancer, Stemness, and Inflammation. Analysis was carried out using the glycan array 4.0 of the Consortium for Functional Glycomics. The 442 glycans tested are plotted on the x-axis; the y-axis shows the relative fluorescence intensity representing the reactivity of the glycans with the antibody. Mannitou exhibits highest reactivity toward the Man3GlcNAc2 structure. Green circles = mannose; blue squares = GlcNAc. Glycosidic linkages (alpha or beta).
In colon carcinoma, Mannitou antibody mainly stained the apical and only weakly the basolateral margin of epithelial cells. Mannitou-stained granular material was also located in the ducts.
Mannitou antibody stained the surface membrane of human adult pancreatic stem cells.