Building a better flu vaccine

By mlayneDecember 5th, 2019in CBMS, Departmental News, Research News

New research from the  Zaia laboratory  has been published in Molecular Proteomics: "Why glycosylation matters in building a better flu vaccine".

Low vaccine efficacy against seasonal influenza A virus (IAV) stems from the ability of the virus to evade existing immunity while maintaining fitness. While most potent neutralizing antibodies bind antigenic sites on the globular head domain of the IAV envelope glycoprotein hemagglutinin (HA), the error-prone IAV polymerase enables rapid evolution of key antigenic sites, resulting in immune escape. Significantly, the appearance of new N-glycosylation consensus sequences (sequons, NXT/NXS, rarely NXC) on the HA globular domain occurs among the more prevalent mutations as an IAV strain undergoes antigenic drift. The appearance of new glycosylation shields underlying amino acid residues from antibody contact, tunes receptor specificity, and balances receptor avidity with virion escape, all of which help maintain viral propagation through seasonal mutations. The determination of site-specific glycosylation of IAV glycoproteins would enable development of vaccines that take advantage of glycosylation-dependent mechanisms whereby virus glycoproteins are processed by antigen presenting cells

Research Discoveries: VEGFR2 glycosylation

Vascular endothelial growth factor receptor 2 (VEGFR2) is a heavily N-glycosylated pro-angiogenic receptor tyrosine kinase. Stimulation of the receptor by vascular endothelial growth factor (VEGF) induces quiescent endothelial cells to proliferate and sprout, and VEGFR2 signaling is also required for tumor growth and metastasis. In a new paper in the Journal of Biological Chemistry by Kevin Brown Chandler and colleagues in the Costello and Rahimi laboratories demonstrated that the glycosylation status of VEGFR2 alters signaling through the receptor. Specifically, sialic acid-capped N-glycans at site N247 oppose ligand-mediated receptor activation, whereas asialo-glycans (lacking sialic acid) favor VEGFR2 activation.

Russek Award Winners in Biochemistry Laboratories

The Henry I. Russek Award Nominating Committee and the Russek Executive Committee would like to announce the winners of this year’s Department of Biochemistry awards.  The honorable mention was awarded to Deborah Chang who is a student in Dr. Zaia’s lab, second prize was awarded to Julia Hicks-Berthet who is a student in Dr. Varelas's lab and the first prize was awarded to Elena Stampouloglou, who is a student in Dr. Varelas's lab.  There is more great news for our department!  The first prize awardee for the Molecular & Translational Medicine program is Rekha Raghunathan, a student in Dr. Zaia’s lab and the first prize awardee for the Genetics & Genomics program is Stefanie Chan, a student in Dr. Perissi’s lab.  Congratulations to all of the awardees (and their mentors)!

So, we'll see you all this Friday, April 26th in Hiebert Lounge for Henry I. Russek Student Achievement Day 2019 and the keynote address to be delivered by Dr. Xiowei Zhuang; her talk is entitled “Illuminating Biology at the Nanoscale and Systems Scale by Imaging”. 

Dr. Costello receives HUPO 2019 Lifetime achievement award

By mlayneJanuary 25th, 2019in CBMS, Departmental News

Catherine Costello Receives Lifetime Achievement in Proteomics Award

Catherine Costello, PhD, the William Fairfield Warren Distinguished Professor at Boston University School of Medicine (BUSM), has received the 2019 Lifetime Achievement in Proteomics Award from the U.S. Human Proteome Organization (U.S. HUPO). This inaugural award recognizes a career of discovery that has made a lasting impact in the field of proteomics, the field which explores the distribution, dynamics and modifications of proteins in cells and living organisms and their relationships to health and disease. ... (link)

Dr. Cathy Costello honored with special issue in The Journal of the American Society for Mass Spectrometry

Costello lab
Costello Laboratory: Dr. Costello is waving.

In recognition of Dr. Catherine Costello's 2017 ASMS Award for a Distinguished Contribution in Mass Spectrometry, the entire June 2018 issue focused on Mass Spectrometry in Glycobiology and Related Fields and was a tribute to Dr. Costello's numerous contributions to the field. The first article in this issue written by Joe Zaia and Veronica Bierbaum describes Dr. Costello's vision and leadership in glycoscience mass spectrometry.

Please also read about the current research in the Costello lab.

New Software Developed for Glycosaminoglycan Analysis

The Zaia laboratory's recent study: “Software for peak finding and elemental composition assignment for glycosaminoglycan tandem mass spectra” has been selected to appear in a special virtual issue of ASBMB journal content on Omics of lipids, glycans and polar metabolites. This paper was selected from hundreds of papers and best represents the exciting advances made in studying these systems over the last three years.Zaia

Glycosaminoglycans (GAGs) covalently linked to proteoglycans are characterized by repeating disaccharide units and variable sulfation patterns along the chain. The Zaia laboratory and others have demonstrated the usefulness of tandem mass spectrometry (MS2) for assigning the structures of GAG saccharides; however, manual interpretation of tandem mass spectra is time-consuming, so computational methods must be employed. The Zaia group developed GAGfinder, the first tandem mass spectrum peak finding algorithm developed specifically for GAGs. GAGfinder is a targeted, brute force approach to spectrum analysis that utilizes precursor composition information to generate all theoretical fragments. GAGfinder also performs peak isotope composition annotation, which is typically a subsequent step for averagine-based methods.

 

 

Research discoveries: glycoprotein glycosylation

New research papers from the Zaia laboratory have established novel strategies for analyzing glycans and glycopeptides.

Glycomics and glycoproteomics analyses by mass spectrometry require efficient front-end separation methods to enable deep characterization of heterogeneous glycoform populations. Chromatography methods azaiapaperre generally limited in their ability to resolve glycoforms using mobile phases that are compatible with online liquid chromatography-mass spectrometry (LC-MS). The adoption of capillary electrophoresis-mass spectrometry methods (CE-MS) for glycomics and glycoproteomics is limited by the lack of convenient interfaces for coupling the CE devices to mass spectrometers. Here, we describe the application of a microfluidics-based CE-MS system for analysis of released glycans, glycopeptides and monosaccharides. We demonstrate a single CE method for analysis three different modalities, thus contributing to comprehensive glycoproteomics analyses. In addition, we explored compatible sample derivatization methods. We used glycan TMT-labeling to improve electrophoretic migration and enable multiplexed quantitation by tandem MS. We used sialic acid linkage-specific derivatization methods to improve separation and the level of information obtained from a single analytical step. Capillary electrophoresis greatly improved glycoform separation for both released glycans and glycopeptides over that reported for chromatography modes more frequently employed for such analyses. Overall, the CE-MS method described here enables rapid setup and analysis of glycans and glycopeptides using mass spectrometry

To learn more:

  1. Khatri, K.; Klein, J. A.; Zaia, J. Use of an informed search space maximizes confidence of site-specific assignment of glycoprotein glycosylation. Anal Bioanal Chem 2017, 409, 607-618. Pubmed Link
  2. Khatri, K.; Klein, J. A.; Haserick, J.; Leon, D. R.; Costello, C. E.; McComb, M. E.; Zaia, J. Microfluidic capillary electrophoresis-mass spectrometry for analysis of monosaccharides, oligosaccharides and glycopeptides. Anal. Chem. 2017, 89, 6645-6655. Pubmed Link

 

Dahoud Breast Cancer Pilot Awards

Congratulations to several Biochemistry faculty who were recently awarded Dahoud Breast Cancer Pilot Awards.

Alla Grishok, PhD, Associate Professor of Biochemistry, Dafne Cardamone, PhD, Instructor, and Catherine Costello, PhD, Director of Center for Biomedical Mass Spectrometry, will study regulation of cancer-promoting Myc protein using a model metastatic breast cancer cell line. Myc binds DNA and activates a large network of genes that together transform normal cells into cancer cells. Myc activity is elevated in most human cancers and is especially relevant for Myc-driven triple (estrogen, progesterone and Her2) negative breast cancer. Dr. Grishok and colleagues will investigate new mechanisms that increase Myc protein activity: 1) adding specific sugar residues, and 2) protein truncation. New compounds that directly inhibit Myc or inhibit enzymes that activate Myc could be developed into new cancer therapies.
COM Dahod_circles_1
Xaralabos Varelas, PhD, Associate Professor of Biochemistry and Stefano Monti, PhD, Associate Professor of Medicine and Biostatistics, will study the causes of aggressive triple negative breast cancers. The team will determine how abnormal signaling networks drive gene expression changes that lead to aggressive breast cancers and then categorize subsets of aggressive breast cancers, thereby better targeting the most effective treatments based on the genes expressed in the tumor.

Cathy Costello receives prestigious mass spectrometry award

Cathy Costello was recently awarded the 2017 Award for a Distinguished Contribution in Mass Spectrometry by the American Society for Mass Spectrometry. This award recognizes a singular significant achievement and was for her pioneering contributions to the development of tandem mass spectrometry of glycans and glycoconjugates. Addtional details of the award can be found on the ASMS web page. Congratulations Cathy!

 

Cathy Costello Elected as AAAS Fellow

By mlayneNovember 25th, 2016in CBMS, Departmental News, Research News

Cocostellongratulations to Cathy Costello for her election as an AAAS Fellow. This is a well-deserved recognition of Dr. Costello’s contributions to mass spectrometry, particularly developing and applying new technologies to advance medicine and increase understanding of biology, and for service to the global community.

Please read article in BUSM News and the full story at the AAAS.