A5024544253- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- Genomics and Phylogenetic Studies
- Neurogenetic and Muscular Disorders Research
- Developmental Biology and Gene Regulation
- Congenital heart defects research
- RNA and protein synthesis mechanisms
- Receptor Mechanisms and Signaling
- Epigenetics and DNA Methylation
- Steroid Chemistry and Biochemistry
- interferon and immune responses
- Mitochondrial Function and Pathology
- RNA regulation and disease
- Neurogenesis and neuroplasticity mechanisms
- Advanced biosensing and bioanalysis techniques
Columbia University Irving Medical Center
2011-2023
Columbia University
2013-2021
University of California, San Diego
2015
Loss of RNA homeostasis underlies numerous neurodegenerative and neuroinflammatory diseases. However, the molecular mechanisms that trigger neuroinflammation are poorly understood. Viral double-stranded (dsRNA) triggers innate immune responses when sensed by host pattern recognition receptors (PRRs) present in all cell types. Here, we report human neurons intrinsically carry exceptionally high levels immunostimulatory dsRNAs identify long 3'UTRs as giving rise to neuronal dsRNA structures....
Neurons born in the embryo can undergo a protracted period of maturation lasting well into postnatal life. How gene expression changes are regulated during and whether they be recapitulated cultured neurons remains poorly understood. Here, we show that mouse motor exhibit pervasive accessibility associated regulatory regions from embryonic till juvenile age. While motifs selector transcription factors, ISL1 LHX3, enriched nascent regions, NFI activity-dependent hormone receptors become more...
Mitochondrial networks exhibit remarkable dynamics that are driven in part by fission and fusion events. However, there other reorganizations of the network do not involve fusion. One such exception is elusive, beads-on-a-string morphological transition mitochondria. During transitions, cylindrical tubes mitochondrial membrane transiently undergo shape changes to a string pearls connected along thin tubes. These have been anecdotally observed many contexts given disparate explanations. Here...
Chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) is a method for the genome-wide de novo discovery of chromatin interactions. Existing computational methods typically fail to detect weak or dynamic interactions because they use peak-calling step that ignores linkage information. We have developed novel called Interaction Discovery (CID) overcome this limitation with an unbiased clustering approach discovery. CID outperforms existing detection improved sensitivity,...
Summary Building a nervous system is protracted process that starts with the specification of individual neuron types and ends formation mature neural circuits. The molecular mechanisms regulate temporal progression maturation in cell remain poorly understood. In this work, we have mapped gene expression chromatin accessibility changes mouse spinal motor neurons throughout their lifetimes. We found both putative regulatory elements are dynamic during first three weeks postnatal life, when...
RNA Polymerase II ChIA-PET data has revealed enhancers that are active in a profiled cell type and the genes regulate through chromatin interactions. The most commonly used computational method for analyzing data, Tool, discovers interaction anchors at spatial resolution is insufficient to accurately identify individual enhancers. We introduce Germ, estimates likelihood any two narrowly defined genomic locations jointly occupied by II. Germ takes blind deconvolution approach simultaneously...
Abstract Transcription factor over-expression is a proven method for reprogramming cells to desired cell type regenerative medicine and therapeutic discovery. However, general the identification of factors create an arbitrary open problem. We examine success rate methods data directed differentiation by testing ability nine computational (CellNet, GarNet, EBSeq, AME, DREME, HOMER, KMAC, diffTF, DeepAccess) correctly discover rank candidate eight target types with known solutions. compare...
ABSTRACT Chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) is a method for the genome-wide de novo discovery of chromatin interactions. Existing computational methods typically fail to detect weak or dynamic interactions because they use peak-calling step that ignores linkage information. We have developed novel called Interaction Discovery (CID) overcome this limitation with an unbiased clustering approach discovery. CID outperforms existing detection improved...