Yi Shi, PhD

The Shi Laboratory 

 

Dr. Shi, an Associate Professor of Pharmacological Sciences and the Director of Protein Engineering and Therapeutics at the Icahn School of Medicine, focuses on developing mass spectrometry-based proteomic techniques to study biology and facilitate drug discovery.

One of the key areas of Dr. Shi's research is the development of proteomic methods and software tools for deconvoluting serum antibody repertoires, specifically Llama VHH antibodies, also known as nanobodies. Nanobodies are small antibody fragments derived from camelid species, and Dr. Shi's lab has leveraged their potential for therapeutic development. They have created powerful proteomic techniques and software tools for high-throughput nanobody drug discovery. Through these efforts, they have discovered thousands of broad neutralizing nanobodies with often unprecedented potency against SARS-CoV-2 and other SARS-like viruses. These nanobodies hold promise as potential solutions to combat current and future pandemics. Dr. Shi and his colleagues have also solved high-resolution structures of these antiviral nanobodies, providing insights into the mechanisms by which they inhibit viral infections. Furthermore, their research has demonstrated the exceptional efficacy of engineered nanobodies for inhalation therapy, suggesting their potential for treating pulmonary infections.

Another active area of research in Dr. Shi's lab involves the development of hybrid techniques that combine machine learning with high-throughput proteomics screening. This integration of machine learning and proteomic approaches aims to enhance protein engineering and design, ultimately advancing the development of "smart" drugs.

Dr. Shi completed his PhD at Baylor College of Medicine in 2011, focusing on proteomic approaches for studying protein ubiquitination. He then pursued a postdoctoral position at the Rockefeller University, where he developed integrative structural proteomic methods to investigate large native macromolecular assemblies, such as the yeast nuclear pore complex. In 2017, Dr. Shi joined the University of Pittsburgh School of Medicine as an Assistant Professor before being recruited to Mount Sinai as an Associate Professor with tenure in 2022.

Dr. Shi's contributions to proteomic techniques, nanobody research, and the integration of machine learning with proteomics hold great potential for advancing drug discovery, particularly in the field of protein engineering and therapeutic development.