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Beyond the Canonical 20 Amino Acids: Expanding the Genetic Lexicon*
The ability to genetically encode unnatural amino acids beyond the common 20 has allowed unprecedented control over the chemical structures of recombinantly expressed proteins. Orthogonal
Versatile strategy for controlling the specificity and activity of engineered T cells
It is demonstrated that a switch-mediated CAR-T approach enables the titration of engineered T-cell antitumor activity, which was observed to be highly advantageous in reducing treatment-related toxicities in vivo.
Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies
It is shown that switches specific for CD19 govern the activity, tissue-homing, cytokine release, and phenotype of switchable CAR-T cells in a dose-titratable manner using xenograft mouse models of B-cell leukemia.
Redirection of genetically engineered CAR-T cells using bifunctional small molecules.
It is demonstrated that a bifunctional small molecule "switch" consisting of folate conjugated to fluorescein isothiocyanate (folate-FITC) can redirect and regulate FITC-specific CAR-T cell activity toward folate receptor (FR)-overexpressing tumor cells.
Identification of the thiazolyl peptide GE37468 gene cluster from Streptomyces ATCC 55365 and heterologous expression in Streptomyces lividans
  • T. Young, C. Walsh
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences
  • 25 July 2011
The gene cluster responsible for production of the elongation factor Tu (EF-Tu)-targeting 29-member thiazolyl peptide GE37468 from Streptomyces ATCC 55365 and its heterologous expression in the model host StrePTomyces lividans is reported, with an unusual β-methyl-δ-hydroxy-proline residue that may increase conformational rigidity of the macrocycle and impart reduced entropic costs of target binding.
An anti-B cell maturation antigen bispecific antibody for multiple myeloma.
A bispecific antibody against B cell maturation antigen (BiFab-BCMA) is reported, which potently and specifically redirects T cells to lyse malignant multiple myeloma cells.
An evolved aminoacyl-tRNA synthetase with atypical polysubstrate specificity.
It is discovered that a p-cyanophenylalanine specific aminoacyl-tRNA synthetase (pCNF-RS) has high substrate permissivity for unnatural amino acids, while maintaining its ability to discriminate against the 20 canonical amino acids.
Antitumor activity of a systemic STING-activating non-nucleotide cGAMP mimetic
A non-nucleotide, small-molecule STING agonist, termed SR-717, that demonstrates broad interspecies and interallelic specificity and functions as a direct cyclic guanosine monophosphate–adenosine monophile mimetic that induces the same “closed” conformation of STING.