A5078847534- Prostate Cancer Treatment and Research
- Cancer-related molecular mechanisms research
- interferon and immune responses
- Genomics and Chromatin Dynamics
- Cytokine Signaling Pathways and Interactions
- RNA Research and Splicing
- Cardiomyopathy and Myosin Studies
- Congenital heart defects research
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Epigenetics and DNA Methylation
- Cardiac Fibrosis and Remodeling
- Mitochondrial Function and Pathology
- Genetic and Kidney Cyst Diseases
- Inflammatory mediators and NSAID effects
- Ferroptosis and cancer prognosis
- DNA Repair Mechanisms
- Estrogen and related hormone effects
- Cancer, Lipids, and Metabolism
- Hormonal and reproductive studies
- Endometriosis Research and Treatment
- Vibrio bacteria research studies
- Renal and related cancers
- Immunotherapy and Immune Responses
- PARP inhibition in cancer therapy
The University of Texas Southwestern Medical Center
2016-2024
Southwestern Medical Center
2017-2024
Center for Human Genetics
2020-2022
McDermott International (United States)
2018-2020
BRD4 belongs to the bromodomain and extraterminal (BET) family of chromatin reader proteins that bind acetylated histones regulate gene expression. Pharmacological inhibition by BET inhibitors (BETi) has indicated antitumor activity against multiple cancer types. We show is essential for repair DNA double-strand breaks (DSBs) mediates formation oncogenic rearrangements engaging non-homologous end joining (NHEJ) pathway. Mechanistically, genome-wide are associated with enhanced acetylation...
Abstract Bats host a large number of zoonotic viruses, including several viruses that are highly pathogenic to other mammals. The mechanisms underlying this rich viral diversity unknown, but they may be linked unique immunological features allow bats act as asymptomatic reservoirs. Vertebrates respond infection by inducing IFNs, which trigger antiviral defenses through IFN-stimulated gene (ISG) expression. Although the IFN system is characterized at genomic level, less known about bat...
DNA replication transforms cohesin rings dynamically associated with chromatin into the cohesive form to establish sister-chromatid cohesion. Here, we show that, in human cells, loading onto chromosomes during early S phase requires replicative helicase MCM2-7 and kinase DDK. Cohesin its loader SCC2/4 (NIPBL/MAU2 humans) associate DDK phosphorylated MCM2-7. This binding does not require activation by CDC45 GINS, but persistence on activated fork-stabilizing replisome components. Inactivation...
Abstract In prostate cancer, androgen deprivation therapy (ADT) enhances the cytotoxic effects of radiotherapy. This effect is associated with weakening DNA damage response (DDR) normally supported by receptor. As a significant number patients will fail combined ADT and radiotherapy, we hypothesized that DDR may be driven receptor splice variants (ARV) induced ADT. Investigating this hypothesis, found ARVs increase clonogenic survival cancer cells after irradiation in an ADT-independent...
Transcriptional dysregulation is a hallmark of prostate cancer (PCa). We mapped the RNA polymerase II-associated (RNA Pol II-associated) chromatin interactions in normal cells and PCa cells. discovered thousands enhancer-promoter, enhancer-enhancer, as well promoter-promoter interactions. These transcriptional hubs operate within framework set by structural proteins - CTCF cohesins are regulated cooperative action master transcription factors, such androgen receptor (AR) FOXA1. By combining...
// Tuyen T. Dang 1 , Jill M. Westcott Erin A. Maine Mohammed Kanchwala 2 Chao Xing Gray W. Pearson 1, 3 Harold C. Simmons Cancer Center, University of Texas, Southwestern Medical Dallas, TX 75390-8807, USA McDermott Center for Human Growth and Disease, Department Pharmacology, Correspondence to: Pearson, email: gray.pearson@utsouthwestern.edu Keywords: invasion, p63, FAT2, Slug, breast cancer Received: January 07, 2016     Accepted: March 28, Published: April 12, 2016...
IDH-mutant astrocytomas are significantly less aggressive than their IDH-wildtype counterparts. We analyzed The Cancer Genome Atlas dataset (TCGA) and identified a small group of IDH-mutant, WHO grade II–III (n = 14) with an unexpectedly poor prognosis characterized by rapid progression to glioblastoma death within 3 years the initial diagnosis. Compared tumors typical, extended progression-free survival in control age-similar patients, rapidly progressing were markedly increased level...
How genetic defects trigger the molecular changes that cause late-onset disease is important for understanding progression and therapeutic development. Fuchs' endothelial corneal dystrophy (FECD) an RNA-mediated caused by a trinucleotide CTG expansion in intron within TCF4 gene. The mutant intronic CUG RNA present at one-two copies per cell, posing challenge to understand how rare can disease. Late-onset FECD uniquely advantageous model studying triggers because: (i) Affected tissue...
Aneuploidy, defective differentiation, and inactivation of the tumor suppressor TP53 all occur frequently during tumorigenesis. Here, we probe potential links among these cancer traits by inactivating in human embryonic stem cells (hESCs). TP53−/− hESCs exhibit increased proliferation rates, mitotic errors, low-grade structural aneuploidy; produce poorly differentiated immature teratomas mice; fail to differentiate into neural progenitor (NPCs) vitro. Genome-wide CRISPR screen reveals...
Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge, and effective tracking requires rapid return of results. Surveillance is typically performed by whole genome sequencing (WGS), which can be financially prohibitive specialized equipment bioinformatic expertise. Genotyping approaches are methods for monitoring SARS-CoV-2 but require continuous adaptation. Fragment analysis may represent an approach improved variant detection. Methods...
Cohesin folds chromosomes via DNA loop extrusion. Cohesin-mediated chromosome loops regulate transcription by shaping long-range enhancer-promoter interactions, among other mechanisms. Mutations of cohesin subunits and regulators cause human developmental diseases termed cohesinopathy. Vertebrate consists SMC1, SMC3, RAD21, either STAG1 or STAG2. To probe the physiological functions cohesin, we created conditional knockout (cKO) mice with
Background In immunosurveillance, bone‐derived immune cells infiltrate the tumor and secrete inflammatory cytokines to destroy cancer cells. However, have evolved mechanisms usurp promote progression. particular, cytokine, interleukin‐1 (IL‐1), is elevated in prostate (PCa) patient tissue serum, promotes PCa bone metastasis. IL‐1 also represses androgen receptor (AR) accumulation activity cells, yet remain viable tumorigenic; suggesting that may contribute AR‐targeted therapy resistance....
Abstract The estrogen receptor (ER) designated ERα has actions in many cell and tissue types that impact glucose homeostasis. It is unknown if these include mechanisms endothelial cells, which have the potential to influence relative obesity, processes adipose skeletal muscle control. Here we show independent of on events tissue, promotes tolerance by enhancing insulin transport muscle. Endothelial ERα-deficient male mice are intolerant resistant, females antidiabetogenic estradiol (E2)...
Significance Prostaglandin E 2 (PGE ), a cervical ripening agent, mediates unique EP2 receptor signaling pathways in human stromal cells targeting its own synthesis by increasing cyclooxygenase-2 (COX-2) and PGE synthase (PTGES) expression decreasing metabolism loss of degradative enzyme 15-hydroxy prostaglandin dehydrogenase (15-PGDH). Here, we show that down-regulation 15-PGDH is crucial for -induced preterm birth. This report details mechanisms action the cervix serves as catalyst ( i )...
Silent subtype III pituitary adenomas (SS-3) are clinically nonfunctional that more aggressive in terms of invasion and risk recurrence than their conventional null cell counterparts. We previously showed these tumors can be distinguished by immunohistochemistry based on the identification a markedly enlarged fragmented Golgi apparatus. To understand molecular correlates differential aggressiveness, we performed whole transcriptome sequencing (RNAseq) 4 SS-3 adenomas. The genes were highly...
Abstract Background The androgen receptor (AR) nuclear transcription factor is a therapeutic target for prostate cancer (PCa). Unfortunately, patients can develop resistance to AR‐targeted therapies and progress lethal disease, underscoring the importance of understanding molecular mechanisms that underlie treatment resistance. Inflammation implicated in PCa initiation progression we have previously reported inflammatory cytokine, interleukin‐1 (IL‐1), represses AR messenger RNA (mRNA)...
ABSTRACT Animal development is mediated by a surprisingly small set of canonical signaling pathways such as Wnt, Hedgehog, TGF-beta, Notch and Hippo pathways. Although once thought to be present only in animals, recent genome sequencing has revealed components these the closest unicellular relatives animals. These findings raise questions about ancestral functions developmental their potential role emergence animal multicellularity. Here, we provide first functional characterization any...