A5033488314- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Monoclonal and Polyclonal Antibodies Research
- Plant nutrient uptake and metabolism
- CRISPR and Genetic Engineering
- Polysaccharides and Plant Cell Walls
- Cancer-related gene regulation
- Prostate Cancer Treatment and Research
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- Protein purification and stability
- Advanced biosensing and bioanalysis techniques
- Genetics and Neurodevelopmental Disorders
- DNA and Nucleic Acid Chemistry
- Congenital heart defects research
- Prostate Cancer Diagnosis and Treatment
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- DNA Repair Mechanisms
- CAR-T cell therapy research
- Enzyme Production and Characterization
- Biofuel production and bioconversion
- Glycosylation and Glycoproteins Research
Howard Hughes Medical Institute
2016-2020
University of California, San Diego
2017-2020
UC San Diego Health System
2020
Stanford University
2016
University of Southern California
2016
National Institutes of Health
2016
NorthShore University HealthSystem
2016
National Cancer Institute
2016
University of Arizona
2016
University of California, Los Angeles
2016
In vertebrates, the conserved Wnt signalling cascade promotes stabilization and nuclear accumulation of beta-catenin, which then associates with lymphoid enhancer factor/T cell factor proteins (LEF/TCFs) to activate target genes. Wnt/beta -catenin is essential for T development differentiation. Here we show that special AT-rich binding protein 1 (SATB1), lineage-enriched chromatin organizer global regulator, interacts beta-catenin recruits it SATB1's genomic sites. Gene expression profiling...
The packaging of newly replicated and repaired DNA into chromatin is crucial for the maintenance genomic integrity. Acetylation histone H3 core domain lysine 56 (H3K56ac) has been shown to play a role in compaction following replication repair Saccharomyces cerevisiae. However, occurrence function such acetylation not reported mammals. Here we show that H3K56 acetylated this modification regulated cell cycle-dependent manner mammalian cells. We also demonstrate acetyltransferase p300...
The 8q24 region harbors multiple risk variants for distinct cancers, including >8 prostate cancer. In this study, we conducted fine mapping of the (127.8–128.8Mb) in search novel associations with common and rare variation 4853 cancer case patients 4678 control subjects African ancestry. All statistical tests were two-sided. We identified three independent at P values less than 5.00×10 –8 , all which replicated studies from Ghana Uganda (combined sample = 5869 patients, 5615 subjects;...
At present almost all the pectinolytic enzymes used for industrial applications are produced by fungi. There a few reports of pectinase production bacterial strains. Therefore, in study, seventy-four strains, isolated from soil and rotten vegetable samples, were screened polygalacturonase production. The strain PG-31, which gave maximum activity, was identified as Bacillus sphaericus (MTCC 7542). Maximal quantities when 16-hours-old inoculum at 7.5% (v/v) medium incubated shaking conditions...
Abstract Genetic variation at the 8q24 locus is linked with greater susceptibility to prostate cancer in men of African ancestry. One such ancestry specific rare variant, rs72725854 (A>G/T) (~6% allele frequency) has been associated a ~2-fold increase risk. However, functional relevance this variant unknown. Here we show that present cancer-specific enhancer locus. Chromatin-conformation capture and dCas9 mediated blocking establish direct regulatory link between lncRNAs PCAT1, PRNCR1...
Cisplatin is an antineoplastic drug administered at suboptimal and intermittent doses to avoid life-threatening effects. Although this regimen shortly improves symptoms in the short term, it also leads more malignant disease long term. We describe a multilayered analysis ranging from chromatin translation-integrating immunoprecipitation sequencing (ChIP-seq), global run-on (GRO-seq), RNA (RNA-seq), ribosome profiling-to understand how cisplatin confers (pre)malignant features by using...
The INK4a/ARF locus encodes important cell-cycle regulators p14ARF, p15INK4b, and p16INK4a. neighboring gene desert to this is the most reproducible GWAS hotspot that harbors one of densest enhancer clusters in genome. However, how multiple enhancers overlap with variants regulate unknown, which an step linking genetic variation associated diseases. Here, we show promoters interact a subset cluster, independent their H3K27ac eRNA levels. Interacting transcriptionally control each other over...
ABSTRACT Retroviral integration has recently been shown to be nonrandom, favoring transcriptionally active regions of chromatin. However, the mechanism for site selection by retroviruses is not clear. We show here occurrence Alu -like motifs in sequences flanking reported viral sites that are significantly different from those obtained randomly picked human genome, suggesting unique primary sequence features exist genomic targeted immunodeficiency virus type 1 (HIV-1). Additionally, these...
Enhancers are transferable DNA elements that regulate target genes within the confines of Topologically Associated Domains (TADs) through Cohesin‐dependent looping. However, potential regulatory functions and mechanisms long‐distance, inter‐TAD enhancer associations remain largely unexplored. We report 17β‐estradiol (E 2 ) rapidly increases spatial proximity a fraction E ‐responsive enhancers located in widely separated TADs. These characterized by recruitment mega‐dalton sized multi...
<h3>Background</h3> T-cell activation requires appropriate strength of stimulation and costimulation. Blocking coinhibitory pathways prevents exhaustion escape. Here, we present the discovery diverse panels lead-quality antibodies, including antibodies against CD3 PD-L1, ready for reformatting into advanced modalities development finely tuned multi-drug approaches a variety tumor targets. <h3>Methods</h3> AlivaMab Discovery Services (ADS) enabled (and PDL-1) antibody from immunized...
<h3>Background</h3> Bispecific antibodies have the potential to unlock novel biology and elicit unique functionalities. There is still an unmet need for effective selective therapeutics cancer treatment. Here, we present discovery of diverse panels lead-quality against two targets reformatting them into bispecifics development dual antagonist therapeutic antibody. <h3>Methods</h3> Binders derived from immunizing AlivaMab<sup>®</sup> Mouse were engineered as bispecific with Fab scFv...
Aging has been largely thought of as a manifestation metabolic malfunctions and physical psychological changes accumulating over time in the body. Recent years have seen seminal research that indicates changing epigenetic landscape individual cells is also one main contributors to process aging, lead term “cellular aging”. INK4/ARF locus on chromosome 9p21 implicated diabetes, heart diseases multiple forms cancer; making it an ideal model study basic rules cellular aging. We identified 33...
Abstract Unliganded nuclear receptors have been implicated in ligand-dependent gene regulation. However, the underlying mechanisms are not fully understood. Here we demonstrate that unliganded ERα binds to specific sites genome thereby pre-marking them as future functional enhancers. Upon ligand exposure, several EREs relatively proximal pre-marked, or persistent, ERα-bound sites. Interestingly, persistent interact extensively, via chromatin looping, with transiently bound forming clustered...
Anticancer drugs with narrow therapeutic window, such as cisplatin, are administrated at suboptimal and intermittent doses to limit their adverse effects in patients. This regimen may allow survival of cancer cells that problematically also gain malignancy result the treatment. Here, we describe a multilayered analysis ranging from chromatin translation (based on ChIP-seq, GRO-seq, RNA-seq, ribosome profiling) comprehensively understand how cisplatin confers new cellular properties...