Dr. Yariv Wine

My fascination with antibody repertoire, along with the lack of technologies for its study, led me to develop a pioneering technology specifically aimed at analyzing antibody repertoire in serum and secretions at health, following disease or vaccine. The approach we use provides us the means to broaden our understanding regarding the development of the adaptive immune response and the complex relationship between antibody encoding B cell V genes and the circulating antibody repertoires.

The used approach integrates several state-of-the-art technologies including next generation sequencing (NGS), shotgun proteomics (LC-MS/MS), advanced bioinformatic tools, peptide arrays and structural analysis.

Collectively, our approach can serve as a platform for antibody discovery as well as a toolkit for the in-depth analysis of the adaptive immune system. This unprecedented analysis should help us answer basic scientific questions concerning the development of the humoral immune response and can be readily translated into essential guidelines for the development of therapeutic antibodies, customized individual treatments towards personalized medicine and new vaccines design.

Projects in the lab include:

• Systematic in-depth multi-approach analysis of Host-Staphylococcus aureus interaction towards next generation of therapeutic and diagnostic solutions

• Trans-placental transfer of antibodies during pregnancy

• Monitoring and profiling the anti-drug antibodies (ADA) repertoire following inflammatory bowl disease (IBD) treatment with anti-TNF-α monoclonal antibodies (Infliximab/Remicade, Humera/Adalimumab)

• Breast milk antibody repertoire analysis and its role in programming the gut microbiome during the first year the neonates life
   
• Antibody repertoire analysis of emerging infectious disease convalescence patients (Ebola, SARS-CoV etc.)

Peer review

1) Cohen-Hadar, N., Wine, Y., Nachliel, E., Huppert, D., Gutman, M., Frolow, F., Freeman, A. (2006).  Monitoring the stability of crosslinked protein crystals biotemplates: A feasibility study. Biotechnology and Bioengineering. 94, 1005-1011.

2) Wine, Y., Cohen-Hadar, N., Freeman, A. & Frolow, F.  (2007). Elucidation of the mechanism and end products of glutaraldehyde crosslinking reaction by X-ray structure analysis. Biotechnology and Bioengineering 98, 711-718.

3) Cohen-Hadar, N., Wine, Y., Lagziel-Simis, S., Moscovich-Dagan, H., Dror, Y., Frolow, F. & Freeman, A.  (2009). Protein Crystal-Mediated Biotemplating. Journal of Porous Media 12, 213-220.

4) Wine, Y., Cohen-Hadar, N., Lamed, R., Freeman, A. & Frolow, F.  (2009). Modification of Protein Crystal Packing by Systematic Mutations of Surface Residues: Implications on Biotemplating and Crystal Porosity. Biotechnology and Bioengineering 104, 444-457.

5) Cohen-Hadar, N., Lagziel-Simis, S., Wine, Y., Frolow, F. & Freeman, A.  (2011). Re-structuring protein crystals porosity for biotemplating by chemical modification of lysine residues. Biotechnology and Bioengineering 108, 1-11.

6) Saggy, I., Wine, Y., Shefet-Carasso, L., Nahary, L., Georgiou, G. & Benhar, I.  (2012). Antibody isolation from immunized animals: comparison of phage display and antibody discovery via V gene repertoire mining. Protein Engineering Design and Selection 25, 539-549.

7) DeKosky, B.J., Ippolito, G.C., Deschner, R.P., Lavinder, J.J., Wine, Y., Rawlings, B.M., Varadarajan, N., Giesecke, C., Dorner, T., Andrews, S.F., Wilson, P.C., Hunicke-Smith, S.P., Willson, C.G., Ellington, A.D. & Georgiou, G.  (2013). High-throughput sequencing of the paired human immunoglobulin heavy and light chain repertoire. Nature Biotechnology 31, 166-169.

8) Cotham, V.C., Wine, Y.,  Brodbelt, J.S.  (2013). Selective 351 nm Photodissociation of Cysteine-Containing Peptides for Discrimination of Antigen-Binding Regions of IgG Fragments in Bottom-Up Liquid Chromatography - Tandem Mass Spectrometry Workflows. Analytical Chemistry 85, 5577-5585.

9) *Wine, Y. (co-first author), *Boutz, D.R., *Lavinder, J.J., Miklos, A.E., Hughes, R.A., Hoi, K.H., Jung, S.T., Horton, A.P., Murrin, E.M., Ellington, A.D., Marcotte, E.M. & Georgiou, G.  (2013). Molecular deconvolution of the monoclonal antibodies that comprise the polyclonal serum response. Proceedings of the National Academy of Sciences of the United States of America 110, 2993-2998.

10) *Lavinder, J.J., *Wine, Y. (co-first author), Giesecke, C.,  Ippolito, G.C., Horton, A.P, Lungu, O.I., Hon Hoi, K., DeKosky, B.J., Murrin, E.M., Wirth, M.M., Ellington, A.D., Dörner, T., Marcotte, E.M., Boutz, D.R., Georgiou, G. (2014). Identification, Dynamics, and Functionality of the Constituent Antibodies within Human Serum after Vaccination. Proceedings of the National Academy of Sciences of the United States of America. 111, 2259-2264.

11) Buch, M., Wine, Y., Dror, Y., Rosenheck, S., Giordano, R., Leal, M.F.R., Popov, N.A., Freeman, A., Frolow, F. (2014). Protein Products Obtained by Site-Preferred Partial Crosslinking in Protein Crystals and “Liberated” by Redissolution. Biotechnology and Bioengineering. 111, 1296-1303.

12) *Boutz, D.R., *Horton, A.P., *Wine, Y. (co-first author), Lavinder, J.J, Georgiou, G., Marcotte, E.M. (2014). Proteomic Identification of Monoclonal Antibodies from Serum. Analytical Chemistry. 86, 4758-4766. 

13)  Lavinder, J.J., Hon Hoi, K., Reddy, S.T., Wine, Y., Georgiou, G. (2014). Systematic Characterization and Comparative Analysis of the Rabbit Immunoglobulin Repertoire. PloS one. 9, e101322.

Invited reviews

14) Lagziel-Simis, S., Cohen-Hadar, N., Moscovich-Dagan, H., Wine, Y. and Freeman, A. (2006). Protein-mediated nanoscale biotemplating. Current opinion in biotechnology. 17, 569-573.

15) Wine Y., Horton AP., Ippolito GC., Georgiou G. (2015). Serology in the 21st century: the molecular-level analysis of the serum antibody repertoire. Current opinion in immunology. 35:89-97.

Conference proceeding

16) Wine, Y., Cohen-Hadar, N.,Lagziel-Simis, S.,  Dror Y., Felix Frolow, F. and Freeman, A. (2010). Adjustment of Protein Crystal Porosity for Biotemplating: Chemical and Protein Engineering Tools. AIP conference Proceedings. 76: 198-203.

Patent Application

Proteomic identification of antibodies. Filed Nov-2012. Published May-2013. US Patent number:  US 20130178370

Crystal Structures

3F2L, 3HU3, 2HUB, 2HTX, 2HU1