Biography
Research Interests:
The diverse and multifaceted interactions between macromolecules and their surrounding environment are vital to the biological function of cells. At both the cellular and molecular level, these interactions are at the root of healthy and diseased states, and form the foundation of human health therapeutics. Our current understanding of the molecular nature of protein-based interactions suggests a dynamic relationship between the 3D structure of cellular machinery, and the resulting biological output.
Our research aims to build, adapt, and innovate structural proteomics platforms as a means of capturing and understanding the dynamic interactions of proteins. Specifically, we focus on the development and deployment of mass spectrometry-based protein labelling techniques like hydrogen-deuterium exchange and cross-linking for the biophysical characterization of protein complexes in increasingly challenging samples. Application of our technology has mainly focused on the study of the mechanisms of therapeutic antibodies and small molecules in the context of cancer therapy, immunotherapy, and emerging infections.
Selected publications
- Rossotti, M.A., van Faassen, H., Tran, A.T., Sheff, J.G., Sandhu, J.K., Duque, D., Hewitt, M., Wen, X., Bavananthasivam, J., Beitari, S., Matte, K., Laroche, G., Giguère, P.M., Gervais, C., Stuible, M., Guimond, J., Perret, S., Hussack, G., Langlois, M.A., Durocher, Y., Tanha, J. Arsenal of nanobodies shows broad-spectrum neutralization against SARS-CoV-2 variants of concern in vitro and in vivo in hamster models. Commun. Biol (2022), 5(1):933, DOI: 10.1038/s42003-022-03866-z
- Sheff, J.G.,Ping, W., Ping, X., Arbour, M., Masson, M., van Faassen, H., Hussack, G., Kemmerich, K., Brunette, E., Stanimirovic, D., Hill, J.J., Kelly, J., Feng, Ni. Defining the epitope of a blood–brain barrier crossing single domain antibody specific for the type 1 insulin-like growth factor receptor. Sci. Rep (2021), 11(1):4284, DOI: 10.1038/s41598-021-83198-w
- Sheff, J.G.,Kelly, J.F., Robotham, A., Sulea, T., Malenfant, F., L’Abbé, D., Duchesne, M., Pelletier, A., Lefebvre, J., Acel, A., Parat, M., Gosselin, M., Cunle, W., Fortin, Y., Baardsnes, J., van Faassen, H., Awrey, S., Chafe, S.C., McDonald, P.C., Dedhar, S., Lenferink, A.E.G. Hydrogen-deuterium exchange mass spectrometry reveals three unique binding responses of mAbs directed to the catalytic domain of hCAIX. MAbs (2021), 13(1):1997072, DOI: 10.1080/19420862.2021.1997072
- Sheff, J.G., Farshidfar, F., Bathe, O.F., Kopciuk, K., Gentile, F., Tuszynski, J., Barakat, K., Schriemer, D.C. Novel allosteric pathway of Eg5 regulation identified through multivariate statistical analysis of hydrogen-exchange mass spectrometry (HX-MS) ligand screening data. Mol. Cell Proteomics (2017), 16(3): 428-437, DOI: 10.1074/mcp.M116.064246
- Sheff, J.G., Hepburn, M., Yu, Y., Lees-Miller, S.P., Schriemer, D.C. Nanospray HX-MS configuration for structural interrogation of large protein systems. Analyst (2017), 142(6): 904-910, DOI: 10.1039/c6an02707e
- Rey, M., Yang, M., Lee, L., Zhang, Y., Sheff, J.G., Sensen, C.W., Mrazek, H., Halada, P., McCarville, J.L., Verdu, E.F., Schriemer, D.C. Addressing proteolytic efficiency in enzymatic degradation therapy for celiac disease. Sci. Rep (2016), 6(1):30980, DOI: 10.1038/srep30980
- Sheff, J.G., Rey, M., Schriemer, D.C. Peptide–column interactions and their influence on back exchange rates in hydrogen/deuterium exchange-MS. J. Am. Soc. Mass. Spectr. (2013), 24(7): 1006-1015, DOI: 10.1007/s13361-013-0639-4