- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Animal Genetics and Reproduction
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Xenotransplantation and immune response
- Pluripotent Stem Cells Research
- RNA Interference and Gene Delivery
- Cancer, Lipids, and Metabolism
- T-cell and B-cell Immunology
- Transplantation: Methods and Outcomes
- Liver Disease Diagnosis and Treatment
- Fungal and yeast genetics research
- Diet, Metabolism, and Disease
- Virus-based gene therapy research
Institute for Systems Biology
2022-2024
University of Pittsburgh Medical Center
2024
New York University
2022-2024
Xenotransplantation of genetically engineered porcine organs has the potential to address challenge organ donor shortage. Two cases porcine-to-human kidney xenotransplantation were performed, yet physiological effects on xenografts and recipients' immune responses remain largely uncharacterized.
Whether synthetic genomes can power life has attracted broad interest in the biology field. Here, we report de novo synthesis of largest eukaryotic chromosome thus far, synIV, a 1,454,621-bp yeast resulting from extensive genome streamlining and modification. We developed megachunk assembly combined with hierarchical integration strategy, which significantly increased accuracy flexibility construction. Besides drastic sequence changes, further manipulated 3D structure synIV to explore...
Genetically engineered mouse models (GEMMs) help us to understand human pathologies and develop new therapies, yet faithfully recapitulating diseases in mice is challenging. Advances genomics have highlighted the importance of non-coding regulatory genome sequences, which control spatiotemporal gene expression patterns splicing many diseases1,2. Including extensive genomic regions, requires large-scale engineering, should enhance quality disease modelling. Existing methods set limits on size...
Summary Whether synthetic genomes can power life has attracted broad interest in the biology field, especially when are extensively modified with thousands of designer features. Here we report de novo synthesis largest eukaryotic chromosome thus far, synIV , a 1,454,621-bp Saccharomyces cerevisiae resulting from extensive genome streamlining and modification. During construction developed megachunk assembly combined hierarchical integration strategy, which significantly increased accuracy...
SUMMARY Enhancer function is frequently investigated piecemeal using truncated reporter assays or single deletion analysis. Thus it remains unclear to what extent enhancer at native loci relies on surrounding genomic context. Using the Big-IN technology for targeted integration of large DNAs, we analyzed regulatory architecture murine Igf2 / H19 locus, a paradigmatic model selectivity. We assembled payloads containing 157-kb functional locus and engineered mutations genetically direct CTCF...
Whether synthetic genomes can power life has attracted broad interest in the biology field, especially when are extensively modified with thousands of designer features. Here we report de novo synthesis largest eukaryotic chromosome thus far, synIV, a 1,454,621-bp Saccharomyces cerevisiae resulting from extensive genome streamlining and modification. During construction developed megachunk assembly method, combined hierarchical integration strategy. This strategy significantly increased...
Overwriting counterselectable markers is an efficient strategy for removing wild-type DNA or replacing it with payload of interest. Currently, one bottleneck genome engineering in mammals the shortage (negative selection) that work robustly without affecting organismal developmental potential. Here, we report a conditional Piga knockout enables proaerolysin-based counterselection mouse embryonic stem cells. The cells show similar proaerolysin resistance as full (non-conditional) deletion...