Synthetic Protein Science and Drug Discovery
Koide Laboratory
We aim to advance the knowledge of how proteins and protein interaction networks work by “synthetic” approaches, i.e. designing and making proteins with novel function. This “learning by building” approach critically tests our understanding of principles that govern protein structure, function and evolution, and it challenges our creativity.
We are now capable of producing highly functional synthetic proteins within weeks. Structural and functional analysis of synthetic proteins not only critically evaluates the effectiveness of our design strategies but also provides broader insights into the molecular mechanism and evolution of protein form and function. Knowledge gained from the synthetic approach complements and very often significantly expands the view from classical studies of natural proteins.
Synthetic proteins serve as novel and transformative tools for basic and translational research in medicine and beyond. We are particularly interested in applying our capability to:
- Development of biologic therapeutics (engineered proteins and antibodies)
- Signal transduction and cancer biology
- Structural biology
- Synthetic biology
News
Vinh has been awarded an F30 predoctoral award from the National Cancer Institute. Congrats!
Our paper on a protein-engineering strategy that enables cryo-EM studies of small GTPases, e.g., RAS, is published in J Mol Biol.
Our paper on the role of tumor-derived lipocalin-2 (LCN2) and novel immunotherapy targeting LCN2 is published in Nature. This is a collaboration with the Papagiannakopoulos lab. See NYU’s press release.
Our paper on HapImmune antibodies targeting neoantigens generated from KRAS(G12C) and the covalent inhibitor adagrasib is published in PNAS.
Our paper on the development of human antibodies selective to the most common hotspot mutation of the HER2 extracellular domain, S310F/Y, is published in Nature Chemical Biology. It also reports cryo-EM structures of the HER2 S310F homodimer and the HER2 S310F–antibody complex.
Our paper on monobodies selective to NRAS (over KRAS and HRAS) is published in Oncogene.
Our paper on the cryo-EM structures of HapImmune antibodies bound to sotorasib-KRAS(G12C) peptides presented by HLA is published in PNAS. These represent our first cryo-EM structures.
Our paper on the development of KRAS(G12D)-selective monobodies and the identification of a new pocket conformation of KRAS(G12D) using the monobodies is published in PNAS (open access).
Our review paper on the use of phage and other display technologies for monobody development is published in Cold Spring Harbor Protocols.
Our paper on monobodies selective to the phosphatase domain of SHP2 and their utility as mechanistic tools is published in J Mol Biol.
The print version of our Cancer Discovery paper is out, accompanied by a commentary and the journal cover illustration for the January issue. It was also highlighted by Science.