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Susan J. Fisher Ph.D.

Adherence mechanisms used by microbial pathogens

Susan J. Fisher Ph.D.

The Fisher lab's major area of investigation is understanding adherence mechanisms used by microbial pathogens. In one project we are testing the hypothesis that bacteria which colonize the oral cavity do so by interacting with the carbohydrate portions of salivary receptors. In general, we use whole-cell ligand blotting (overlaying blots of salivary glycoproteins with bacteria) to identify interactions between individual salivary molecules and particular bacterial species. This technique led to the identification of a highly glycosylated, proline-rich glycoprotein (PRG) as the major Fusobacterium nucleatum receptor in saliva. We then determined, using mass spectrometry and nuclear magnetic resonance spectroscopy, the complete structure of the subset of PRG oligosaccharides that carry the bacterial receptor activity. We used this same experimental strategy to study the interaction between streptococci and the low-molecular-weight salivary mucin. Very recently we showed that this glycoprotein carries sulfated sialyl Lex structures and is a ligand for L-selectin. This observation has interesting implications for leukocyte trafficking in the oral cavity.

Selected publications:

Drake PM, Schilling B, Niles RK, Prakobphol A, Li B, Jung K, Cho W, Braten M, Inerowicz HD, Williams K, Albertolle M, Held JM, Iacovides D, Sorensen DJ, Griffith OL, Johansen E, Zawadzka AM, Cusack MP, Allen S, Gormley M, Hall SC, Witkowska HE, Gray JW, Regnier F, Gibson BW, Fisher SJ. Lectin chromatography/mass spectrometry discovery workflow identifies putative biomarkers of aggressive breast cancers. J Proteome Res. 2012 Apr 6; 11(4):2508-20.

Aghajanova L, Shen S, Rojas AM, Fisher SJ, Irwin JC, Giudice LC. Comparative transcriptome analysis of human trophectoderm and embryonic stem cell-derived trophoblasts reveal key participants in early implantation. Biol Reprod. 2012 Jan; 86(1):1-21.

Witkowska HE, Hall SC, Fisher SJ. Breaking the bottleneck in the protein biomarker pipeline. Clin Chem. 2012 Feb; 58(2):321-3.

Fisher SJ, Giudice LC. SGK1: a fine balancing act for human pregnancy. Nat Med. 2011; 17(11):1348-9.

Bárcena A, Muench MO, Kapidzic M, Gormley M, Goldfien GA, Fisher SJ. Human placenta and chorion: potential additional sources of hematopoietic stem cells for transplantation. Transfusion. 2011 Nov; 51 Suppl 4:94S-105S.

Genbacev O, Donne M, Kapidzic M, Gormley M, Lamb J, Gilmore J, Larocque N, Goldfien G, Zdravkovic T, McMaster MT, Fisher SJ. Establishment of human trophoblast progenitor cell lines from the chorion. Stem Cells. 2011 Sep; 29(9):1427-36.

Liu H, Yang L, Khainovski N, Dong M, Hall SC, Fisher SJ, Biggin MD, Jin J, Witkowska HE. Automated iterative MS/MS acquisition: a tool for improving efficiency of protein identification using a LC-MALDI MS workflow. Anal Chem. 2011 Aug 15; 83(16):6286-93.

Hunkapiller NM, Gasperowicz M, Kapidzic M, Plaks V, Maltepe E, Kitajewski J, Cross JC, Fisher SJ. A role for Notch signaling in trophoblast endovascular invasion and in the pathogenesis of pre-eclampsia. Development. 2011 Jul; 138(14):2987-98.

Schanz A, Winn VD, Fisher SJ, Blumenstein M, Heiss C, Hess AP, Kruessel JS, Mcmaster M, North RA. Pre-eclampsia is associated with elevated CXCL12 levels in placental syncytiotrophoblasts and maternal blood. Eur J Obstet Gynecol Reprod Biol. 2011 Jul; 157(1):32-7.

Krtolica A, Larocque N, Genbacev O, Ilic D, Coppe JP, Patil CK, Zdravkovic T, McMaster M, Campisi J, Fisher SJ. GROa regulates human embryonic stem cell self-renewal or adoption of a neuronal fate. Differentiation. 2011 Apr; 81(4):222-32.