Andrew Lu

Engineered caspases directly rewire mutant Ras to cell death

Lukas Moeller, Andrew Lu, Kevin Ho, Evan Zhang et autres

As central executioners of cell death, caspases that activate exclusively in diseased cells would provide powerful and specific therapeutic agents. Natural caspase regulation exhibits two universal features that facilitate the engineering of such caspases: proximity-induced subunit assembly and modular separation of substrate …

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Double dissociation of the effects of volitional control on perceptual selection and maintenance in multistable visual perception

David W. Bressler, Sean Noah, Andrew Lu, M. A. Silver

Stimuli that give rise to multistable percepts are powerful tools for understanding the psychological and neural processes and mechanisms that create conscious perception. Research on multistable perception has resulted in substantial insights regarding the stimulus and configural factors that influence perceptual interpretations …

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De novo design of phosphotyrosine peptide binders

Magnus S. Bauer, Jason Z. Zhang, Kejia Wu, Gyu Rie Lee et autres

ABSTRACT Phosphorylation on tyrosine is a key step in many signaling pathways. Despite recent progress in de novo design of protein binders, there are no current methods for designing binders that recognize phosphorylated proteins and peptides; this is a challenging problem as …

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Engineered protein circuits for cancer therapy

Andrew Lu, Lukas Moeller, Stephen Moore, Kevin Ho et autres

A central challenge in cancer therapy is selectively killing cancer cells while minimizing resistance. Here, we engineer modular protease-based protein circuits that sense mutant RAS, the most frequently mutated oncogene in cancer, and conditionally activate cell death. Delivered transiently as mRNA in …

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Method of moments framework for differential expression analysis of single-cell RNA sequencing data

Min Cheol Kim, Rachel E. Gate, David Lee, Andrew Tolopko et autres

Differential expression analysis of single-cell RNA sequencing (scRNA-seq) data is central for characterizing how experimental factors affect the distribution of gene expression. However, distinguishing between biological and technical sources of cell-cell variability and assessing the statistical significance of quantitative comparisons between cell …

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Synthetic protein circuits for programmable control of mammalian cell death

Shiyu Xia, Andrew Lu, Victoria Tobin, Kaiwen Luo et autres

Natural cell death pathways such as apoptosis and pyroptosis play dual roles: they eliminate harmful cells and modulate the immune system by dampening or stimulating inflammation. Synthetic protein circuits capable of triggering specific death programs in target cells could similarly remove harmful …

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Stoichiometric expression of messenger polycistrons by eukaryotic ribosomes (SEMPER) for compact, ratio-tunable multi-gene expression from single mRNAs

Mengtong Duan, Ishaan Dev, Andrew Lu, Mei Yi You et autres

ABSTRACT Applications of mammalian synthetic biology increasingly require the ability to express multiple proteins at user-determined stoichiometries from single, compactly encoded transcripts. Here we present an approach for expressing multiple open reading frames (ORFs) from a single transcript, taking advantage of the …

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memento: Generalized differential expression analysis of single-cell RNA-seq with method of moments estimation and efficient resampling

Min Cheol Kim, Rachel E. Gate, David Lee, Andrew Lu et autres

Abstract Differential expression analysis of scRNA-seq data is central for characterizing how experimental factors affect the distribution of gene expression. However, it remains challenging to distinguish biological and technical sources of cell-cell variability and to assess the statistical significance of quantitative comparisons …

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Multi-context genetic modeling of transcriptional regulation resolves novel disease loci

Michael Thompson, Mary Grace Gordon, Andrew Lu, Anchit Tandon et autres

A majority of the variants identified in genome-wide association studies fall in non-coding regions of the genome, indicating their mechanism of impact is mediated via gene expression. Leveraging this hypothesis, transcriptome-wide association studies (TWAS) have assisted in both the interpretation and discovery …

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Single-cell RNA-seq reveals cell type–specific molecular and genetic associations to lupus

Richard K. Perez, M. Grace Gordon, Meena Subramaniam, Min Cheol Kim et autres

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Knowledge of circulating immune cell types and states associated with SLE remains incomplete. We profiled more than 1.2 million peripheral blood mononuclear cells (162 cases, 99 controls) with multiplexed single-cell RNA sequencing (mux-seq). …

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Synthetic mammalian signaling circuits for robust cell population control

Yitong Ma, Mark W. Budde, Michaëlle N. Mayalu, Junqin Zhu et autres

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Multi-context genetic modeling of transcriptional regulation resolves novel disease loci

Michael Thompson, Mary Grace Gordon, Andrew Lu, Anchit Tandon et autres

Abstract A majority of the variants identified in genome-wide association studies fall in non-coding regions of the genome, indicating their mechanism of impact is mediated via gene expression. Leveraging this hypothesis, transcriptome-wide association studies (TWAS) have assisted in both the interpretation and …

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