Area of Interest Biopolymer structural studies; development of mass spectral methods
The objective of our research is to establish the detailed structures of biopolymers in order to understand their structure-activity relationships as they influence or reflect biological processes related to health, growth and development, and disease. Our particular focus for new method development is on the needs of glycobiology, since carbohydrates and their conjugates (glycoproteins, glycolipids, etc.) are involved in targeting and immune system recognition, nervous system growth and development, infection, parasite response, carcinogenesis, and other critical processes. The techniques for full structural characterization of these complex molecules are much less developed than are methods for linear biopolymers (proteins and oligonucleotides). Recent introduction of new mass spectral ionization methods and rapid progress in means for mass separation and detection now make it possible to perform structural studies on low picomole amounts of samples even when they are complex mixtures.
In our research program we are refining and extending the tools of mass spectrometry and are applying them to studies of biopolymers undertaken with collaborators at BUSM and other institutions around and outside the US. Our laboratory is a Resource Center sponsored by the NIH National Institute of General Medical Sciences.
Jurgen Sanes – Visiting Scientist (Based at MGH, Immunology) Bernd Stahl – Visiting Scientist (based at Nutricia Research, Utrecht, The Netherlands)
Representative Publications
Chandler KB, Mehta N, Leon DR, Suscovich TJ, Alter G, Costello CE. Multi-isotype Glycoproteomic Characterization of Serum Antibody Heavy Chains Reveals Isotype- and Subclass-Specific N-Glycosylation Profiles. Mol Cell Proteomics. 2019 Apr; 18(4):686-703. PMID:33451651
Wei J, Tang Y, Ridgeway ME, Park MA, Costello CE, Lin C. Accurate Identification of Isomeric Glycans by Trapped Ion Mobility Spectrometry-Electronic Excitation Dissociation Tandem Mass Spectrometry. Anal Chem. 2020 10 06; 92(19):13211-13220. PMID:32865981
Azab E, Chandler KB, Uda Y, Sun N, Hussein A, Shuwaikan R, Lu V, Costello CE, McComb ME, Divieti Pajevic P. Osteocytes control myeloid cell proliferation and differentiation through Gsa-dependent and -independent mechanisms. FASEB J. 2020 Aug; 34(8):10191-10211.PMID:32557809
Fuzita FJ, Chandler KB, Haserick JR, Terra WR, Ferreira C, Costello CE. N-glycosylation in Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins. Comp Biochem Physiol B Biochem Mol Biol. 2020 Aug – Sep; 246-247:110464.PMID:32553552
Wei J, Tang Y, Bai Y,Zaia J, Costello CE, Hong P, Lin C. Toward Automatic and Comprehensive Glycan Characterization by Online PGC-LC-EED MS/MS. Anal Chem. 2020 01 07; 92(1):782-791. PMID: 31829560
Yura Y, Chong BSH, Johnson RD, Watanabe Y, Tsukahara Y, Ferran B, Murdoch CE, Behring JB, McComb ME, Costello CE, Janssen-Heininger YMW, Cohen RA, Bachschmid MM, Matsui R. Endothelial cell-specific redox gene modulation inhibits angiogenesis but promotes B16F0 tumor growth in mice. FASEB J. 2019 12; 33(12):14147-14158.PMID:31647879
Tsybin YO, Bondarenko PV, Artaev VB, Zubarev RA, Costello CE. The Russian Mass Spectrometry Interest Group at ASMS: Over 20 Years of Science and Water Polo. J Am Soc Mass Spectrom. 2019 Oct 01; 30(10):2178-2182. PMID: 31951721
Chandler KB, Leon DR, Kuang J, Meyer RD, Rahimi N, Costello CE. N-Glycosylation regulates ligand-dependent activation and signaling of vascular endothelial growth factor receptor 2 (VEGFR2). J Biol Chem. 2019 08 30; 294(35):13117-13130.PMID:31308178
Sorvillo N, Mizurini DM, Coxon C, Martinod K, Tilvawala R, Cherpokova D, Salinger AJ, Seward RJ, Staudinger C, Weerapana E, Shapiro NI, Costello CE, Thompson PR, Wagner DD. Plasma Peptidylarginine Deiminase IV Promotes VWF-Platelet String Formation and Accelerates Thrombosis After Vessel Injury. Circ Res. 2019 08 16; 125(5):507-519. PMID:31248335
Brown Chandler K, Costello CE, Rahimi N. Glycosylation in the Tumor Microenvironment: Implications for Tumor Angiogenesis and Metastasis. Cells. 2019 Jun 05; 8(6).PMID:31195728
Magistrado-Coxen P, Aqeel Y, Lopez A, Haserick JR, Urbanowicz BR, Costello CE, Samuelson J. The most abundant cyst wall proteins of Acanthamoeba castellanii are lectins that bind cellulose and localize to distinct structures in developing and mature cyst walls. PLoS Negl Trop Dis. 2019 05; 13(5):e0007352.PMID:31095564
Campbell MP, Abrahams JL, Rapp E, Struwe WB, Costello CE, Novotny M, Ranzinger R, York WS, Kolarich D, Rudd PM, Kettner C. The minimum information required for a glycomics experiment (MIRAGE) project: LC guidelines. Glycobiology. 2019 05 01; 29(5):349-354. PMID:30778580
McDonald AJ, Leon DR, Markham KA, Wu B, Heckendorf CF, Schilling K, Showalter HD, Andrews PC, McComb ME, Pushie MJ, Costello CE, Millhauser GL, Harris DA. Altered Domain Structure of the Prion Protein Caused by Cu2+ Binding and Functionally Relevant Mutations: Analysis by Cross-Linking, MS/MS, and NMR. Structure. 2019 06 04; 27(6):907-922.e5. PMID:30956132Complete list can be found at BU Profiles