Antibodies play an essential role in basic biological research and drug development. The NIH and pharmaceutical industry have placed enormous resources on antibody R&D. For example, the 2016 antibody market size reached $100 billion with ~300 major suppliers offering more than 2 million antibodies for basic research. Contradictory to these heroic efforts is the fact that over 75% of these antibodies do not work properly. Low-quality, batch-to-batch variations, and difficulty in manufacturing and storage are among the main issues, making technologies that address these limitations of ultimate importance. Camelid VHH single-chain antibodies (nanobodies (Nbs)) are compelling new class of antibodies that are characterized by their small size, ease of bioengineering, superior solubility and thermo-stability, as well as low toxicity in humans. Although Nbs are considered highly promising next generation agents for biomedical sciences and therapeutics, robust, in-depth, high-quality identification and analysis of antigen-specific Nbs remain challenging. Current technologies often lack sufficient depth, sensitivity and rigor towards high-quality binders; there is also a scarcity of tools for comprehensive structural analysis of antigen-Nb complexes, and methods for quantitative characterization of large repertoires of soluble Nb proteins. Overall, substantial technical hurdles toward developing superior “next-generation” antibody/Nb technologies exist.


Our research has been focused on the development of cutting-edge mass spectrometry-based proteomics technologies for structural and functional analysis of biomolecules. The main focus of the lab now is to develop new hybrid technologies that integrate advanced genomics, proteomics, informatics, structure modeling approaches, and animal models  for  the discovery and characterization of antigen-specific nanobodies.  Currently, there are several directions that we are exploring:

I):   High-throughput, next-generation nanobody proteomics technologies.

II):  New informatics tools for structure-functional analysis of antibody proteome.

III): Novel antibody-based therapy and biomedical applications.

We'd like to thank the supports from 

© 2016-2019 by the Shi Lab University of Pittsburgh Pittsburgh PA 15213

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