A5013146182- Advancements in Photolithography Techniques
- Genomics and Chromatin Dynamics
- NF-κB Signaling Pathways
- Integrated Circuits and Semiconductor Failure Analysis
- Industrial Vision Systems and Defect Detection
- RNA Interference and Gene Delivery
- Genomics, phytochemicals, and oxidative stress
- CRISPR and Genetic Engineering
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Advanced Surface Polishing Techniques
- RNA regulation and disease
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- CAR-T cell therapy research
- Electron and X-Ray Spectroscopy Techniques
- Single-cell and spatial transcriptomics
- Hemoglobinopathies and Related Disorders
- RNA modifications and cancer
- Prenatal Screening and Diagnostics
- Ubiquitin and proteasome pathways
- interferon and immune responses
- RNA and protein synthesis mechanisms
National Institutes of Health
2020-2024
National Heart Lung and Blood Institute
2024
National Institute of Technology Andhra Pradesh
2024
National Institute on Deafness and Other Communication Disorders
2020-2023
National University of Singapore
2019-2023
Editas Medicine (United States)
2018-2023
Samsung (India)
2023
Dhanalakshmi Srinivasan Group of Institutions
2022
University of Virginia Health System
2010-2019
GlobalFoundries (United States)
2016-2018
Though AsCas12a fills a crucial gap in the current genome editing toolbox, it exhibits relatively poor efficiency, restricting its overall utility. Here we isolate an engineered variant, "AsCas12a Ultra", that increased efficiency to nearly 100% at all sites examined HSPCs, iPSCs, T cells, and NK cells. We show Ultra maintains high on-target specificity thereby mitigating risk for off-target making ideal complex therapeutic applications. achieved simultaneous targeting of three clinically...
The chromatin immunoprecipitation (ChIP) assay is widely used to capture interactions between and regulatory proteins, but it unknown how stable most native are. Although live-cell imaging suggests short-lived at tandem gene arrays, current methods cannot measure rapid binding dynamics single-copy genes. We show, by using a modified ChIP with subsecond temporal resolution, that the time dependence of formaldehyde cross-linking can be extract in vivo on off rates for site-specific varying...
Abstract TNFα is a key mediator of immune, chemotherapy and radiotherapy-induced cytotoxicity, but several cancers, including head neck squamous cell carcinomas (HNSCC), display resistance to due activation the canonical NFκB pro-survival pathway. However, direct targeting this pathway associated with significant toxicity; thus, it vital identify novel mechanism(s) contributing in cancer cells. Here, we demonstrate that expression proteasome-associated deubiquitinase USP14 significantly...
Multiplexed genome editing with DNA endonucleases has broad application, including for cellular therapies, but chromosomal translocations, natural byproducts of inducing simultaneous genomic breaks, have not been explored in detail. Here we apply various CRISPR-Cas nucleases to edit the T cell receptor alpha and beta 2 microglobulin genes human primary cells comprehensively evaluate frequency stability resulting translocations. A thorough translocation analysis using three orthogonal methods...
Digital real-time PCR assay rapidly measures single telomere lengths and uncovers maintenance mechanisms in cancer.
Sub-Resolution Assist Features (SRAFs) are used in optical lithography to improve the manufacturing process window (PW). They added mask shapes create a denser environment that improves printability of target design on wafer. As critical dimensions (CDs) need be patterned shrink with every technology generation, SRAFs have become and key component enabling processes manufacturable windows. The size placement must carefully optimized provide maximum benefit main feature while avoiding any...
Homogeneous assay platforms for measuring protein–ligand interactions are highly valued due to their potential high-throughput screening. However, the implementation of these multiplexed assays in conventional microplate formats is considerably expensive large amounts reagents required and need automation. We implemented a homogeneous fluorescence anisotropy-based binding an automated microfluidic chip simultaneously interrogate >2300 pairwise interactions. demonstrated utility this platform...
Due to its intricacy, dermatology presents the most challenging and uncertain terrain for diagnosis. Skin conditions like Carcinoma Melanoma are frequently very identify in early stages much more define independently. The use of pattern recognition models automate detection has been studied by a number writers. This research describes novel Deep Convolutional Neural Network (DCNN) Disease Detection. photographs skin would undergo processing remove unwanted noise as well improve photos....
Head and neck squamous cell carcinoma (HNSCC) remains a prevalent diagnosis with current treatment options that include radiotherapy immune-mediated therapies, in which tumor necrosis factor-α (TNFα) is key mediator of cytotoxicity. However, HNSCC other cancers often display TNFα resistance due to activation the canonical IKK–NFκB/RELA pathway, activated by, induces expression of, cellular inhibitors apoptosis proteins (cIAPs). Our previous studies have demonstrated IAP inhibitor birinapant...
TNFα is a key mediator of immune and radiotherapy-induced cytotoxicity, but many cancers, including head neck squamous cell carcinomas (HNSCC), display TNF resistance due to activation the canonical IKK-NF-κB/RELA pro-survival pathway. However, toxicities associated with direct targeting pathway point need identify mechanism(s) contributing synthetic lethal targets overcome such in cancer cells. Here, RNAi screening for modulators TNFα-NF-κB reporter activity survival unexpectedly implicated...
Digital PCR (dPCR) is an important tool for precise nucleic acid quantification in clinical setting, but the limited multiplexing capability restricts its applications quantitative gene panel profiling. Here, this work describes melt-encoded-tags expanded optical readout digital (METEOR-dPCR), a simple two-step assay that enables simultaneous of large arbitrary genes dPCR platform. Target are quantitatively converted into DNA tags with unique melting temperatures through ligation approach....
Genome-wide analysis of cell-free DNA methylation profile is a promising approach for sensitive and specific detection many cancers. However, scaling such assays clinical translation impractical because the high cost whole-genome bisulfite sequencing. We show that small fraction GC-rich genome highly enriched in CpG sites disproportionately harbors most cancer-specific signature. Here, we report on simple effective heat enrichment CpG-rich regions sequencing (Heatrich-BS) platform allows...
5-Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are the most abundant DNA modifications that have important roles in gene regulation. Detailed studies of these different epigenetic marks aimed at understanding their combined effects dynamic interconversion are, however, hampered by inability current methods to simultaneously measure both modifications, particularly samples with limited quantities. We present analysis restriction enzyme for simultaneous detection multiple epigenomic...
Genome-wide profiling of copy number alterations and DNA methylation in single cells could enable detailed investigation into the genomic epigenomic heterogeneity complex cell populations. However, current methods to do this require sample processing cleanup steps, lack consistency, or are biased their representation. Here, we describe a novel single-tube enzymatic method, Analysis by Restriction Enzyme (DARE), perform deterministic whole genome amplification while preserving information....
The TATA-box Binding Protein (TBP) plays a central role in regulating gene expression and is the first step process of pre-initiation complex (PIC) formation on promoter DNA. lifetime TBP at site controlled by several cofactors including Modifier transcription 1 (Mot1), an essential TBP-associated ATPase. Based ensemble measurements, Mot1 can use adenosine triphosphate (ATP) hydrolysis to displace from DNA various models for how this activity coupled transcriptional regulation have been...