A5100362495- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Protein Degradation and Inhibitors
- Cellular transport and secretion
- Prostate Cancer Treatment and Research
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cancer Research and Treatments
- Lipid Membrane Structure and Behavior
- Bioinformatics and Genomic Networks
- Cancer-related Molecular Pathways
- Cancer-related molecular mechanisms research
- DNA Repair Mechanisms
- Synthesis and bioactivity of alkaloids
- Gut microbiota and health
- Cancer therapeutics and mechanisms
- Enzyme function and inhibition
- RNA Interference and Gene Delivery
- RNA regulation and disease
- Peptidase Inhibition and Analysis
- Estrogen and related hormone effects
- Clinical Nutrition and Gastroenterology
- Biomedical Text Mining and Ontologies
University of British Columbia
2012-2024
University of Colorado Denver
2024
University of Colorado Anschutz Medical Campus
2024
Cedars-Sinai Medical Center
2024
PathAI (United States)
2023
Agency for Science, Technology and Research
2023
Genome Institute of Singapore
2023
Kyoto University
2022-2023
National University of Singapore
2022
Columbia University
2009-2020
Abstract Numerous cancers, including prostate cancer (PCa), are addicted to transcription programs driven by specific genomic regions known as super-enhancers (SEs). The robust of genes at such SEs is enabled the formation phase-separated condensates factors and coactivators with intrinsically disordered regions. androgen receptor (AR), main oncogenic driver in PCa, contains large co-recruited transcriptional coactivator mediator complex subunit 1 (MED1) androgen-dependent PCa cells, thereby...
Abstract The Long-read RNA-Seq Genome Annotation Assessment Project (LRGASP) Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. consortium generated over 427 million sequences from cDNA and direct RNA datasets, encompassing human, mouse, manatee species, using different protocols sequencing platforms. These data were utilized by developers address challenges in transcript isoform detection quantification, as well de novo identification....
The structures of β class carbonic anhydrases (β-CAs) determined so far fall into two distinct subclasses based on the observed coordination catalytic zinc (Zn2+) ion. subclass β-CAs that coordinate Zn2+ tetrahedrally with four protein-derived ligands is represented by orthologues from Porphyridium purpureum, Escherichia coli, and Mycobacterium tuberculosis. Here we present structure an additional member subclass, Haemophilus influenzae, as well detailed kinetic analysis, revealing...
Poison inhibitors of DNA topoisomerase II (TOP2) are clinically used drugs that cause cancer cell death by inducing damage, which mechanism action is also associated with serious side effects such as secondary malignancy and cardiotoxicity. In contrast, TOP2 catalytic induce limited have low cytotoxicity, effective in suppressing proliferation. They been sought after to be prospective anticancer therapies. Herein the discovery new described. A druggable pocket protein at its binding domain...
Furin is a dibasic endopeptidase responsible for the proteolytic maturation of many precursor proteins in secretory and endocytic pathways mammalian cells. The levels furin expression most cells are very low, this has hampered attempts to identify intracellular compartments which endogenous localized. We have used specific antibody reagent sequence carboxy terminus perform immunofluorescent staining cell lines. This was sensitive enough detect various For part, confined juxtanuclear...
The P21-activated kinases (PAK) are emerging antitumor therapeutic targets. In this paper, we describe the discovery of potent PAK inhibitors guided by structure-based drug design. addition, efflux pyrrolopyrazole series was effectively reduced applying multiple medicinal chemistry strategies, leading to a that orally active in inhibiting tumor growth vivo.
Membrane-induced amphipathic helices (m-AH) can act as membrane curvature sensors by binding preferentially to hydrophobic lipid packing defects enriched in curved surfaces. Reliance on hydrophobicity and for is enhanced when electrostatic interactions are weak. We probed the role of modifying protein charge sensing two m-AH-containing proteins, CTP:phosphocholine cytidylyltransferase (CCT) α-synuclein (α-syn). The m-AH domains both proteins flanked disordered tails with multiple...
The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a versatile RNA-binding protein playing critical role in alternative pre-mRNA splicing regulation cancer. Emerging data have implicated hnRNP as central player regulatory circuit involving its direct transcriptional control by c-Myc oncoprotein and the production of constitutively active ligand-independent splice variant androgen receptor, AR-V7, which promotes castration-resistant prostate cancer (CRPC). As there an urgent need...
Lin28 is a pluripotency factor that regulates cancer cell stem-like phenotypes to promote development and therapy-resistant tumor progression. It acts through its cold shock domain zinc knuckle (ZKD) interact with the Let-7 pre-microRNA block biosynthesis. Chemical inhibition of from interacting presents therapeutic strategy for therapy. Herein, we present computer-aided small molecules by in silico screening 18 million compounds ZINC20 library, followed biological validation 163 predicted...
Resistance to drug treatments is common in prostate cancer (PCa), and the gain-of-function mutations human androgen receptor (AR) represent one of most dominant drivers progression resistance AR pathway inhibitors (ARPI). Previously, we evaluated vitro response 24 mutations, identified men with castration-resistant PCa, five antagonists. In current work, 44 additional PCa-associated mutants, reported literature, thus expanded study effect darolutamide a total 68 mutants. Unlike other...
To restore dystrophin protein in various mutation patterns of Duchenne muscular dystrophy (DMD), the multi-exon skipping (MES) approach has been investigated. However, only limited techniques are available to induce a large deletion cover target exons spread over several hundred kilobases. Here, we utilized CRISPR-Cas3 system for MES induction and showed that dual crRNAs could at exon 45-55 region (∼340 kb), which can be applied types DMD patients. We developed two-color SSA-based reporter...
Haemophilus influenzae β-carbonic anhydrase (HICA) is hypothesized to be an allosteric protein that regulated by the binding of bicarbonate ion a non-catalytic (inhibitory) site controls ligation Asp44 catalytically essential zinc ion. We report here X-ray crystallographic structures two variants (W39F and Y181F) involved in active-site variant (D44N) incapable forming strong ligand. The alteration Trp39 Phe increases apparent Ki for inhibition 4.8-fold. While W39F Y181F are very similar...
Bacteria with multiple drug resistance (MDR) have become a global issue worldwide, and hundreds of thousands people's lives are threatened every year. The emergence novel MDR strains insufficient development new antimicrobial agents the major reasons that limit choice antibiotics for treatment bacterial infection. Thus, preserving clinical value current could be one effective approaches to resolve this problem. Here we identified numerous small RNAs were downregulated in isolates Pseudomonas...
Resistance to androgen-receptor (AR) directed therapies is, among other factors, associated with Myc transcription factors that are involved in development and progression of many cancers. Overexpression N-Myc protein prostate cancer (PCa) leads its transformation advanced neuroendocrine (NEPC) currently has no approved treatments. a short half-life but acts as an NEPC stimulator when it is stabilized by forming protective complex Aurora A kinase (AURKA). Therefore, dual-inhibition AURKA...
Abstract Each cell type in a solid tissue has characteristic transcriptome and spatial arrangement, both of which are observable using modern omics assays. However, the common practice is still to ignore information when clustering cells identify types. In fact, location typically considered only solving related, but distinct, problem demarcating domains (which could include multiple types). We present BANKSY, an algorithm that unifies domain segmentation by constructing product space...