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Articles by Leo Scheller
Drug-controlled CAR T cells through the regulation of cell–cell interactions - Nature Chemical Biology
Abstract Chimeric antigen receptor (CAR) T cell therapy is constrained by on-target, off-tumor toxicities and cellular exhaustion because of chronic antigen exposure. CARs incorporating small-molecule controlled on- and off-switches can enhance both safety and therapeutic efficacy but their design is limited by the scarcity of nonimmunogenic protein elements responsive to nonimmunosuppressive, clinically approved drugs with favorable pharmacodynamics.
Targeting protein–ligand neosurfaces with a generalizable deep learning tool - Nature
Abstract Molecular recognition events between proteins drive biological processes in living systems1. However, higher levels of mechanistic regulation have emerged, in which protein–protein interactions are conditioned to small molecules2,3,4,5. Despite recent advances, computational tools for the design of new chemically induced protein interactions have remained a challenging task for the field6,7.
Drug-controlled CAR-T cells through the regulation of cell-cell interactions
Abstract CAR T-cell therapy is constrained by on-target, off-tumor toxicities as well as cellular exhaustion due to chronic antigen exposure. CARs comprising small-molecule controlled switches can enhance both safety and therapeutic efficacy but are limited by the scarcity of non-immunogenic protein elements responsive to non-immunosuppressive, clinically approved drugs with favorable pharmacodynamics.
Protein-based bandpass filters for controlling cellular signaling with chemical inputs - Nature Chemical Biology
Abstract Biological signal processing is vital for cellular function. Similar to electronic circuits, cells process signals via integrated mechanisms. In electronics, bandpass filters transmit frequencies with defined ranges, but protein-based counterparts for controlled responses are lacking in engineered biological systems.
Rational design of small‐molecule responsive protein switches
Small-molecule responsive protein switches are powerful tools for controlling cellular processes. These switches are designed to respond rapidly and specifically to their inducer. They have been used in numerous applications, including the regulation of gene expression, post-translational protein modification, and signal transduction. Typically, small-molecule responsive protein switches consist of two proteins that interact with each other in the presence or absence of a small-molecule.
Rationally designed protein bandpass filters for controlling cellular signaling with chemical inputs
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Author Correction: A modular degron library for synthetic circuits in mammalian cells - Nature Communications
Correction to: Nature Communications https://doi.org/10.1038/s41467-019-09974-5, published online 01 May 2019 The original version of the Supplementary Information associated with this Article was missing Supplementary Table 1. The HTML has been updated to include a corrected version of the Supplementary Information.
Bottom-up de novo design of functional proteins with complex structural features
Abstract De novo protein design has enabled the creation of new protein structures. However, the design of functional proteins has proved challenging, in part due to the difficulty of transplanting structurally complex functional sites to available protein structures. Here, we used a bottom-up approach to build de novo proteins tailored to accommodate structurally complex functional motifs.
A modular degron library for synthetic circuits in mammalian cells
Abstract Tight control over protein degradation is a fundamental requirement for cells to respond rapidly to various stimuli and adapt to a fluctuating environment. Here we develop a versatile, easy-to-handle library of destabilizing tags (degrons) for the precise regulation of protein expression profiles in mammalian cells by modulating target protein half-lives in a predictable manner.
Caffeine-inducible gene switches controlling experimental diabetes
After drinking an average cup of coffee, blood levels of caffeine peak in the low micromolar range29,30, so for the present purpose, we required a novel caffeine sensor system for non-toxic (Supplementary Fig. 1), physiologically relevant concentrations. To capture these concentrations, we established a caffeine-inducible protein dimerization system in mammalian cells to create different types of gene switches.
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