A5046456211- Galectins and Cancer Biology
- Phagocytosis and Immune Regulation
- Cancer-related gene regulation
- Hippo pathway signaling and YAP/TAZ
- Cancer Mechanisms and Therapy
- Sperm and Testicular Function
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Cancer-related molecular mechanisms research
- Ovarian cancer diagnosis and treatment
- Cancer Cells and Metastasis
- Reproductive Biology and Fertility
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Gastric Cancer Management and Outcomes
- Cancer Research and Treatments
- RNA Research and Splicing
- Birth, Development, and Health
- MicroRNA in disease regulation
- Animal Genetics and Reproduction
- Peptidase Inhibition and Analysis
- Circular RNAs in diseases
- Nanoparticle-Based Drug Delivery
- Chromosomal and Genetic Variations
- Cholangiocarcinoma and Gallbladder Cancer Studies
Hubei University of Automotive Technology
2025
Baylor College of Medicine
2004-2024
The University of Texas MD Anderson Cancer Center
2015-2023
Cornell University
2015
University of Nevada, Reno
2007
Mayo Clinic
2003
Houston Medical Center
2003
Mayo Clinic in Arizona
2003
University of Maryland, College Park
2000
A pharmacologic approach to male contraception remains a longstanding challenge in medicine. Toward this objective, we explored the spermatogenic effects of selective small-molecule inhibitor (JQ1) bromodomain and extraterminal (BET) subfamily epigenetic reader proteins. Here, report potent inhibition testis-specific member BRDT, which is essential for chromatin remodeling during spermatogenesis. Biochemical crystallographic studies confirm that occupancy BRDT acetyl-lysine binding pocket by...
Dicer is an evolutionarily conserved ribonuclease III that necessary for microRNA (miRNA) processing and the synthesis of small interfering RNAs from long double-stranded RNA. Although it has been shown plays important roles in mammalian germline early embryogenesis, functions Dicer-dependent pathways somatic cells female reproductive tract are unknown. Using a transgenic line which Cre recombinase driven by anti-Müllerian hormone receptor type 2 promoter, we conditionally inactivated Dicer1...
Nuage are amorphous ultrastructural granules in the cytoplasm of male germ cells as divergent Drosophila, Xenopus, and Homo sapiens. Most nuage cytoplasmic ribonucleoprotein structures implicated diverse RNA metabolism including regulation PIWI-interacting (piRNA) synthesis by PIWI family (i.e., MILI, MIWI2, MIWI). MILI is prominent embryonic early post-natal also called germinal that often associated with mitochondria intermitochondrial cement. We find GASZ (Germ cell protein Ankyrin...
Abstract Mounting evidence suggests that the Hippo coactivator Yes-associated protein 1 (YAP1) is a major mediator of cancer stem cell (CSC) properties, tumor progression, and therapy resistance as well often terminal node many oncogenic pathways. Thus, targeting YAP1 may be novel therapeutic strategy for types tumors with high expression, including esophageal adenocarcinoma. However, effective inhibitors are currently lacking. Here, we identify small molecule (CA3) not only has remarkable...
Peritoneal carcinomatosis (PC) occurs frequently in patients with gastric adenocarcinoma (GAC) and confers a poor prognosis. Multiplex profiling of primary GACs has been insightful but the underpinnings PC's development/progression remain largely unknown. We characterised exome/transcriptome/immune landscapes PC cells from GAC aiming to identify novel therapeutic targets.We performed whole-exome sequencing (WES) whole transcriptome (RNA-seq) on 44 specimens (43 PC) including an integrative...
Abstract Purpose: Transcriptionally induced chimeric RNAs are an important emerging area of research into molecular signatures for biomarker and therapeutic target development. Salivary exosomes represent a relatively unexplored, but convenient, noninvasive cancer discovery. However, the potential cancer-derived exosomal in saliva as biomarkers is unknown. Here, we explore clinical utility salivary GOLM1-NAA35 RNA (seG-NchiRNA) esophageal squamous cell carcinoma (ESCC). Experimental Design:...
Abstract Background PVT1 has emerged as an oncogene in many tumor types. However, its role Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) is unknown. The aim of this study was to assess the BE/EAC progression uncover therapeutic value against EAC. Methods expression assessed by qPCR normal, BE, EAC tissues statistical analysis performed determine association (stage, metastases, survival). antisense oligonucleotides (ASOs) were tested for their antitumor activity vitro vivo....
Peritoneal carcinomatosis (PC; malignant ascites or implants) occurs in approximately 45% of advanced gastric adenocarcinoma (GAC) patients and associated with a poor survival. The molecular events leading to PC are unknown. yes-associated protein 1 (YAP1) oncogene has emerged many tumour types, but its clinical significance is unclear. Here, we investigated the role YAP1 potential as therapeutic target.Patient-derived cells, patient-derived xenograft (PDX) orthotopic (PDO) models were used...
Objective Many cancers engage embryonic genes for rapid growth and evading the immune system. SOX9 has been upregulated in many tumours, yet role of mediating immunosuppressive tumour microenvironment is unclear. Here, we aim to dissect SOX9-mediated cancer stemness attributes advanced gastric adenocarcinoma (GAC) novel therapeutic discoveries. Methods Bulk RNAseq/scRNA-seq, patient-derived cells/models extensive functional studies were used identify expression functions its target vitro...
Men or mice with homozygous serine/threonine kinase 33 (
Chromatin remodeling is a major event that occurs during mammalian spermiogenesis, the process of spermatid maturation into spermatozoa. Nuclear condensation spermiogenesis accomplished by replacing somatic histones (linker histone H1 and core histones) testis-specific linker histone, H1t, with transition proteins protamines. It has long been thought H1t only all are replaced proteins, subsequently protamines spermiogenesis. Here, we report identification characterization spermatid-specific...
Infertility affects an estimated 7% of men worldwide, nearly a quarter whom are diagnosed as idiopathic. The genetic etiologies idiopathic male infertility unknown, partly due to lack simple diagnostic techniques. Moreover, the transmission risk such defects offspring born from assisted reproductive techniques is increasingly becoming concern for physicians and infertile couples. We explored feasibility obtaining full-length mRNAs transcriptionally inert human spermatozoa in semen...
MicroRNAs (miRNAs) are small non-coding RNAs that mediate post-transcriptional gene silencing. Over 700 human miRNAs have currently been identified, many of which mutated or de-regulated in diseases. Here we report the identification novel through deep sequencing RNAome (<30 nt) over 100 tissues cell lines derived from female reproductive organs both normal and disease states. These specimens include ovarian epithelium cancer, endometrium endometriomas, uterine myometrium smooth muscle...
Abstract Although named “ovarian cancer,” it has been unclear whether the cancer actually arises from ovary, especially for high-grade serous carcinoma (HGSC), also known as ovarian cancer, most common and deadliest cancer. In addition, tumor suppressor p53 is frequently mutated gene in HGSC. However, can cause HGSC remains unknown. this study, we bred a mutation, p53R172H, into conditional Dicer-Pten double-knockout (DKO) mice, mouse model duplicating human HGSC, to generate triple-mutant...
Esophageal cancer is a lethal disease that often resistant to therapy. Alterations of YAP1 and CDK6 are frequent in esophageal cancer. Deregulation both molecules may be responsible for therapy resistance.Expressions were examined cells tissues using immunoblotting immunohistochemistry. expression was induced examine YAP1-mediated activation its association with radiation resistance. Pharmacologic genetic inhibitions performed dissect the mechanisms assess antitumor effects vitro vivo.YAP1...
Objective Gastro-oesophageal cancers (GEC) are resistant to therapy and lead poor prognosis. The cancer stem cells (CSCs) antiapoptotic pathways often confer resistance. We sought elucidate the antitumour action of a BCL-2 inhibitor, AT101 in GEC vitro, vivo clinical trial. Methods Extensive preclinical studies vitro were carried out establish mechanism on targeting CSCs proteins. A pilot trial patients with was completed AT-101 added standard chemoradiation. Results Overexpression MCL-1...
We identified a testis-specific gene encoding protein containing BTB/POZ domain and six kelch repeats, which we named k e l ch h omo og 10 (KLHL10). KLHL10 displays high evolutionary conservation in mammals, as evidenced by 98.7% amino acid identity between mouse human KLHL10. is exclusively expressed the cytoplasm of elongating elongated spermatids (steps 9-16). generated Klhl10 null allele 129S6/SvEv embryonic stem cells, obtained 47 chimeras from independent cell lines. Whereas...
AbstractIn somatic cells, abscission, the physical separation of daughter cells at completion cytokinesis, requires CEP55, ALIX, and TSG101. In contrast, cytokinesis is arrested prior to abscission in differentiating male germ that are interconnected by TEX14-positive intercellular bridges. We have previously shown targeted deletion TEX14 disrupts bridges all causes sterility. Although these findings demonstrate essential for spermatogenesis, it remains be how other proteins come together...
Abstract The peritoneal cavity is a common site of gastric adenocarcinoma (GAC) metastasis. Peritoneal carcinomatosis (PC) resistant to current therapies and confers poor prognosis, highlighting the need identify new therapeutic targets. CD47 conveys “don't eat me” signal myeloid cells upon binding its receptor regulatory protein alpha (SIRPα), which helps tumor circumvent macrophage phagocytosis evade innate immune responses. Previous studies demonstrated that blockade alone results in...
Lipooligosaccharide (LOS) has been implicated in the adhesion and invasion of host epithelial cells. We examined adhesive invasive abilities isogenic gonococcal opacity-associated outer membrane protein-negative, pilus-positive (Opa-Pil+) Neisseria gonorrhoeae strains expressing genetically defined LOS. Strain F62 (Opa-Pil+), lacto-N-neotetraose galNac-lacto-N-neotetraose LOS, its derivative that expressed only LOS (F62 Delta lgtD), adhered to, invaded, to same extent human cervical...
Activation of cancer stem cell signaling is central to acquired resistance therapy in esophageal (EC). ABT-263, a potent Bcl-2 family inhibitor, active against many tumor types. However, effect ABT-263 on EC cells and their resistant counterparts are unknown. Here we report that inhibited proliferation induced apoptosis human chemo-resistant counterparts. The combination with 5-FU had synergistic lethal effects amplified does not depend fully its inhibition BCL-2 proteins cells. To further...
Hippo/YAP1 signaling is a major regulator of organ size, cancer stemness, and aggressive phenotype. Thus, targeting YAP1 may provide novel therapeutic strategy for tumors with high expression in esophageal (EC). Chromatin immunoprecipitation (ChiP) quantitative ChiP-PCR were used to determine the regulation chromatin remodeling protein bromodomain-containing 4 (BRD4) on YAP1. The role bromodomain extraterminal motif (BET) inhibitor JQ1, an established BRD4 inhibitor, inhibition EC cells was...
Gastric adenocarcinoma (GAC) is a lethal disease with limited therapeutic options. Genetic alterations in chromatin remodelling gene AT-rich interactive domain 1A (ARID1A) and mTOR pathway activation occur frequently GAC. Targeting the mechanistic target of rapamycin (mTOR) unselected patients has failed to show survival benefit. A deeper understanding GAC might identify subset that can benefit from inhibition.Genomic ARID1A were analysed Mouse gastric epithelial cells CK19-Cre-Arid1Afl/fl...