A5090742132- Acute Kidney Injury Research
- Heme Oxygenase-1 and Carbon Monoxide
- Traumatic Brain Injury and Neurovascular Disturbances
- Nitric Oxide and Endothelin Effects
- Cancer, Hypoxia, and Metabolism
- Telomeres, Telomerase, and Senescence
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Sirtuins and Resveratrol in Medicine
- Cancer Cells and Metastasis
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Epigenetics and DNA Methylation
- Advanced biosensing and bioanalysis techniques
- Chronic Kidney Disease and Diabetes
- Autophagy in Disease and Therapy
- Immune Response and Inflammation
- Cancer Research and Treatments
- Protein Degradation and Inhibitors
- Cancer-related Molecular Pathways
- Sepsis Diagnosis and Treatment
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Multiple Myeloma Research and Treatments
- Sarcoma Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
Agency for Science, Technology and Research
2017-2024
Genome Institute of Singapore
2017-2023
National University Cancer Institute, Singapore
2020
National University of Singapore
2020
University of Arkansas for Medical Sciences
2009-2012
Acute kidney injury is a frequent and serious complication of sepsis. To better understand the development sepsis-induced acute injury, we performed first time-dependent studies to document changes in renal hemodynamics oxidant generation peritubular microenvironment using murine cecal ligation puncture (CLP) model CLP caused an increase capillary permeability at 2 hours, followed by decreases mean arterial pressure, blood flow (RBF), perfusion 4 which were sustained through 18 hours. The...
Cell state transitions control the functional behavior of cancer cells. Epithelial-to-mesenchymal transition (EMT) confers stem cell-like properties, enhanced tumorigenicity and drug resistance to tumor cells, while mesenchymal-epithelial (MET) reverses these phenotypes. Using high-throughput chemical library screens, retinoids are found be potent promoters MET that inhibit in basal-like breast cancer. defined by reprogramming lipid metabolism. Retinoids bind cognate nuclear receptors, which...
Oxidative stress has been implicated to play a major role in multiorgan dysfunction during sepsis. To study the mechanism of oxidant generation acute kidney injury (AKI) sepsis, we developed an vitro model sepsis using primary cultures mouse cortical tubular epithelial cells exposed serum (2.5–10%) collected from mice at 4 h after induction by cecal ligation and puncture (CLP) or Sham (no sepsis). CLP produced concentration-dependent increase nitric oxide (NO) (nitrate + nitrite) release 6...
Abstract Cancer cells undergo transcriptional reprogramming to drive tumor progression and metastasis. Using cancer cell lines patient-derived organoids, we demonstrate that loss of the negative elongation factor (NELF) complex inhibits breast development through downregulating epithelial-mesenchymal transition (EMT) stemness-associated genes. Quantitative multiplexed Rapid Immunoprecipitation Mass spectrometry Endogenous proteins (qPLEX-RIME) further reveals a significant rewiring...
Abstract Alternative lengthening of telomeres (ALT) supports telomere maintenance in 10–15% cancers, thus representing a compelling target for therapy. By performing anti-cancer compound library screen on isogenic cell lines and using extrachromosomal telomeric C-circles, as bona fide marker ALT activity, we identify receptor tyrosine kinase inhibitor ponatinib that deregulates mechanisms, induces dysfunction, reduced ALT-associated synthesis, targets, vivo, ALT-positive cells. Using...
Sepsis-induced acute kidney injury (AKI) is a complex disease characterized by generation of inducible nitric oxide synthase (iNOS)–derived reactive nitrogen species (RNS) the renal tubular epithelium. While most in vitro models sepsis use combinations lipopolysaccharide and cytokines to simulate exposure inflammatory mediators thought play role sepsis, relevance these limited. To address need for model that more closely mimics microenvironment during we developed an where mIMCD-3 (murine...
Proteasome inhibitors, such as bortezomib and carfilzomib, have shown efficacy in anti-cancer therapy hematological diseases but not solid cancers. Here, we found that liposarcomas (LPS) are susceptible to proteasome inhibition, identified drugs synergize with selinexor, an inhibitor of XPO1-mediated nuclear export. Through quantitative protein profiling phospho-kinase arrays, potential mode actions this combination, including interference ribosome biogenesis inhibition pro-survival kinase...
Abstract Enabling replicative immortality is one prominent feature of cancer cells. To that end, cells activate means to elongate their telomeres. While 85% cancers re-express telomerase, around 15% all rely on the ALT (Alternative Lengthening Telomeres) mechanism. Despite its frequency, no clinically approved ALT-targeted therapy exists date. By performing anti-cancer compound library screen isogenic cell lines and using extrachromosomal telomeric C-circles, as a bona fide marker activity,...
Sepsis-induced acute kidney injury (AKI) is a systemic inflammatory response that initiates oxidative stress in the leading to tubular injury. To study mechanism of oxidant generation epithelial cells during sepsis, we exposed primary cultures mouse serum collected from mice at 4h after induction sepsis by cecal ligation and puncture (CLP) or Sham (no sepsis). CLP produced concentration-dependent cytotoxicity (p < .05 10% vs. Sham). Prior there was decrease ATP serum) an increase NO,...
Our studies in a murine model of cecal ligation and puncture (CLP)‐induced sepsis show that iNOS‐derived reactive nitrogen species (RNS) generated by the tubular epithelium play major role acute kidney injury (AKI) associated with sepsis. Unfortunately, sepsis‐induced AKI is complex disease difficult to vitro . To address need study mechanism oxidant generation injury, we developed new, more relevant where mIMCD‐3 (murine epithelial cells) are treated media containing 5% serum collected from...
Previous studies by our laboratory have shown that sepsis produces a rapid inflammatory response in the kidney leads to tubular injury. There are no vitro models adequately replicate microenvironment during sepsis. To address this need, we established new model of sepsis‐induced renal epithelial injury using serum from septic mice and mouse cell line. mIMCD‐3 cells (epithelial inner medullary collecting duct) were treated with media containing 5% collected at 4h undergone sham surgery (Sham)...
Sepsis affects over 750,000 patients annually and the development of acute kidney injury (AKI) during sepsis nearly doubles mortality rate to 75%. We have recently published that dietary antioxidant, resveratrol (RSV), can improve function survival in cecal ligation puncture (CLP) model mouse. Since RSV has been reported lead activation sirtuin1 (SIRT1), which may be protective, we investigated relationship between SIRT1 acetylation p53. enzyme activity was increased at 10 18h post CLP as...
On the Cover: Co-culture of established mesenchymal and ureteric bud cell lines in three-dimensional (3D) matrices results simple organoid structures.3D co-cultures were immunofluorescently stained for periepithelial capillary-like cells (AQP-1, green) collecting duct (EndoA cytokeratin, red).Nuclei are blue.
Abstract Triple-negative breast cancer (TNBC), as immunohistochemically defined by its estrogen receptor (ER)-negative, progesterone (PR)-negative and human epidermal growth factor receptor-2 (HER2)-negative status, is an important subtype due to biologically aggressive behavior limited treatment options available. TNBC associated with overall poorer prognosis, higher risk of disease recurrence/progression shorter duration response, i.e., resistance. Treatment resistance may be largely...