A5005686919- Cancer Research and Treatments
- 3D Printing in Biomedical Research
- Gene Regulatory Network Analysis
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- CRISPR and Genetic Engineering
- Viral Infections and Outbreaks Research
- Image Processing Techniques and Applications
- Virus-based gene therapy research
- SARS-CoV-2 and COVID-19 Research
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- Bacteriophages and microbial interactions
- Biomedical and Engineering Education
- Cancer Cells and Metastasis
- Viral gastroenteritis research and epidemiology
- Neural dynamics and brain function
- MicroRNA in disease regulation
- Neural Networks and Applications
- Retinal Development and Disorders
- Viral Infections and Immunology Research
- PARP inhibition in cancer therapy
- Viral Infectious Diseases and Gene Expression in Insects
- Neuroscience and Neuropharmacology Research
- Industrial Vision Systems and Defect Detection
National Center on Addiction and Substance Abuse at Columbia University
2020-2024
Columbia University
2016-2023
Rockefeller University
2020-2023
California Institute of Technology
2014-2016
Howard Hughes Medical Institute
2015
University of California, San Diego
2008
Cell populations can be strikingly heterogeneous, composed of multiple cellular states, each exhibiting stochastic noise in its gene expression. A major challenge is to disentangle these two types variability and understand the dynamic processes mechanisms that control them. Embryonic stem cells (ESCs) provide an ideal model system address this issue because they exhibit heterogeneous expression functionally important regulatory factors. We analyzed individual ESCs using single-molecule...
The ability of bacteria and viruses to selectively replicate in tumors has led synthetic engineering new microbial therapies. Here we design a cooperative strategy whereby S. typhimurium transcribe deliver the Senecavirus A RNA genome inside host cells, launching potent oncolytic viral infection. Then, engineer virus require bacterially delivered protease order achieve virion maturation, demonstrating bacterial control over virus. This work extends therapeutics genomes, governing population...
Significance An emerging area of synthetic biology is the engineering bacteria to diagnose and treat various diseases in body. However, lack physiologically relevant vitro testing environments rapidly screen bacterial therapies limits their development for clinical use. Here, we develop a platform that enables parallel long-term monitoring engineered multicellular spheroids. Using this system, screened tumor-targeting deliver library anticancer molecules via gene circuits. We demonstrate...
ADP-ribosylation is a highly dynamic posttranslational modification frequently studied in stress response pathways with recent attention given to its role viral infection. Notably, the alphaviruses encode catalytically active macrodomains capable of ADP-ribosylhydrolase (ARH) activities, implying remodeling cellular ADP-ribosylome. This report decouples mono- and poly-ARH contributions macrodomain function using newly engineered Sindbis virus (SINV) mutant attenuated activity. Our findings...
Retinal Müller glial cells, in addition to providing homeostatic support retinal neurons, have been shown engage modulation of neuronal activity and regulate vasomotor responses the retina, among other functions. Calcium-mediated signaling cells has implicated play a significant role intracellular intercellular interactions necessary carry out these Although basic molecular mechanisms calcium described, dynamics not fully explored. Here, we provide quantitative characterization an vitro...
The ability to extrapolate gene expression dynamics in living single cells requires robust cell segmentation, and one of the challenges is amorphous or irregularly shaped boundaries. To address this issue, we modified U-Net architecture segment fluorescence widefield microscopy images quantitatively evaluated its performance. We also proposed a novel loss function approach that emphasizes segmentation accuracy on boundaries encourages shape feature preservation. With 97% sensitivity, 93%...
Synthetic biology has led to advances in both our understanding and engineering of genetic circuits that affect spatial temporal behaviors living cells. A growing array native synthetic such as oscillators, pattern generators, cell–cell communication systems been studied, which exhibit spatiotemporal properties. To better understand the design principles these circuits, there is a need for versatile precise methods patterning cell populations various configurations. In this study, we develop...
Abstract The ability of bacteria and viruses to selectively replicate in tumors has led synthetic engineering new microbial therapies. In our system, Salmonella been programmed produce Senecavirus A (SVA)-RNA launch an SVA infection bacterially-infected cancer cells. Utilizing time-lapse microscopy, we visualize S. typhimurium invasions into cells their subsequent delivery multiple picornaviral species. S.-typhimurium-viral-RNA vitro identified a small-cell-lung cell line, H446, as promising...
Abstract Synthetic biology is transforming therapeutic paradigms by engineering living cells and microbes to intelligently sense respond diseases including inflammation 1,2 , infections 3-5 metabolic disorders 6,7 cancer 8,9 . However, the ability rapidly engineer new therapies far outpaces throughput of animal-based testing regimes, creating a major bottleneck for clinical translation 10,11 In vitro approaches address this challenge have been limited in scalability broad-applicability....
The ability to extrapolate gene expression dynamics in living single cells requires robust cell segmentation, and one of the challenges is amorphous or irregularly shaped boundaries. To address this issue, we modified U-Net architecture segment fluorescence widefield microscopy images quantitatively evaluated its performance. We also proposed a novel loss function approach that emphasizes segmentation accuracy on boundaries encourages shape feature preservation. With 97% sensitivity, 93%...
Abstract Engineering tumor-homing bacteria to locally deliver therapeutics is an emerging approach for next-generation living therapy cancer. However, the lack of physiologically-relevant in vitro testing environments rapidly and quantitatively characterize complex multicellular interactions cancer cells a major bottleneck clinical translation. We recently developed 3D coculture platform that grow various within necrotic core spheroids, recapitulating selective bacterial growth solid tumor...
Summary While decades of research have elucidated many steps in the alphavirus lifecycle, earliest replication dynamics remained unclear. This missing time window has obscured early replicase strand synthesis behavior and prevented elucidation how resulting activity gives rise to a superinfection exclusion environment, one fastest competitive phenotypes among viruses. Using quantitative live-cell single-molecule imaging, we characterize preferences viral situ , measure protein kinetics...