A5073264150- Cancer-related molecular mechanisms research
- Lymphoma Diagnosis and Treatment
- Sarcoma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- PARP inhibition in cancer therapy
- Ovarian cancer diagnosis and treatment
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- DNA Repair Mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Cell death mechanisms and regulation
- Neuroblastoma Research and Treatments
- Amino Acid Enzymes and Metabolism
- interferon and immune responses
- Ferroptosis and cancer prognosis
- Phagocytosis and Immune Regulation
- Metabolism, Diabetes, and Cancer
- Advanced Breast Cancer Therapies
- Acute Kidney Injury Research
- Advanced Electron Microscopy Techniques and Applications
- Bioinformatics and Genomic Networks
- CRISPR and Genetic Engineering
- Muscle and Compartmental Disorders
Providence College
2022-2024
Heinrich Heine University Düsseldorf
2019-2024
Düsseldorf University Hospital
2022-2024
GlaxoSmithKline (United States)
2023
Johns Hopkins University
2022
Nephrology Center of Maryland
2022
University of British Columbia
2017-2021
BC Cancer Agency
2021
The RAS family of proto-oncogenes are among the most commonly mutated genes in human cancers and predict poor clinical outcome. Several mechanisms underlying oncogenic transformation well documented, including constitutive signaling through RAF-MEK-ERK proproliferative pathway as PI3K-AKT prosurvival pathway. Notably, control redox balance has also been proposed to contribute transformation. However, how homeostasis between reactive oxygen species (ROS) antioxidants, which have opposing...
Oncogenic KRAS is the key driver oncogene for several of most aggressive human cancers. One feature oncogenic expression an early increase in cellular reactive oxygen species (ROS) which promotes transformation if cells manage to escape cell death, mechanisms remain incompletely understood. Here, we identify that as compared WT isogenic systems renders more resistant ferroptosis, a recently described type regulated necrosis. Mechanistically, find with mutant show specific lack...
Abstract Cancer cells must overcome anoikis (detachment-induced death) to successfully metastasize. Using proteomic screens, we found that distinct oncoproteins upregulate IL1 receptor accessory protein (IL1RAP) suppress anoikis. IL1RAP is directly induced by oncogenic fusions of Ewing sarcoma, a highly metastatic childhood sarcoma. inactivation triggers and impedes dissemination sarcoma cells. Mechanistically, binds the cell-surface system Xc− transporter enhance exogenous cystine uptake,...
Abstract Energetic stress compels cells to evolve adaptive mechanisms adjust their metabolism. Inhibition of mTOR kinase complex 1 (mTORC1) is essential for cell survival during glucose starvation. How mTORC1 controls viability starvation not well understood. Here we show that the effectors eukaryotic initiation factor 4E binding proteins 1/2 (4EBP1/2) confer protection mammalian and budding yeast under Mechanistically, 4EBP1/2 promote NADPH homeostasis by preventing NADPH-consuming fatty...
Abstract Glioblastoma is the most common malignant primary brain tumor. To date, clinically relevant biomarkers are restricted to isocitrate dehydrogenase (IDH) gene 1 or 2 mutations and O6-methylguanine DNA methyltransferase ( MGMT ) promoter methylation. Long non-coding RNAs (lncRNAs) have been shown contribute glioblastoma pathogenesis could potentially serve as novel biomarkers. The clinical significance of HOXA Transcript Antisense RNA, Myeloid-Specific HOTAIRM1 was determined by...
Abstract Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a stress-responsive hub that inhibits the translation eEF2, and consequently mRNA elongation, in response to hypoxia nutrient deprivation. EEF2K also involved DNA damage but its role crosslinks, as induced by cisplatin, not known. Here we found eEF2K critical mediate cellular cisplatin. We uncovered deficient cells are more resistant cisplatin treatment. Mechanistically, deficiency blunts activation of associated ATM ATR...
Introduction: In North America, obtaining access for percutaneous nephrolithotomy (PCNL) is often not performed by urologists. Hands-on training sessions help to ensure this skill continues within the urological community. An ex-vivo pig kidney model was developed simulation. This uses porcine tissues with a fluoroscopic C-arm and standard PCNL equipment. The bullseye or triangulation techniques are both possible. We propose as high-fidelity tool teaching access.
 Methods: kidney, fat,...
Abstract Ferroptosis is an iron-dependent form of regulated cell death arising from excessive lipid peroxidation. While seminal work described that oncogenic RAS transformation drives synthetic lethal vulnerability to archetypal ferroptosis inducers including erastin (eradicator and ST-expressing cells) RSL3 (Ras selective 3), more recent suggest signaling may confer resistance. Thus, the impact on cellular response still unclear. Here, we provide unifying evidence across multiple models...
In the phase 2 OVARIO trial (NCT03326193) investigating niraparib-bevacizumab first-line maintenance, median progression-free survival was 14.2 months (95% confidence interval (CI) 8.6 to 16.8) for patients with homologous recombination (HR)-proficient (HRp) epithelial ovarian cancer, and 12.1 CI8.0-not evaluated) undefined HR status. However, real-world data are limited who receive maintenance therapy. The COMB1NE study describes clinical outcomes (time treatment discontinuation; time next...
ABSTRACT Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a stress-responsive hub that inhibits the translation eEF2, and consequently mRNA elongation, in response to hypoxia nutrient deprivation. EEF2K also involved DNA damage but its role crosslinks, as induced by cisplatin, not known. Here we found eEF2K critical mediate cellular cisplatin. We uncovered deficient cells are more resistant cisplatin treatment. Mechanistically, deficiency blunts activation of associated ATM ATR...
Background: Antimicrobials are drugs that often misused and inappropriate antimicrobial prescribing results in poor clinical outcome drug resistance. Monitoring regulation of use is currently being done by the Department Health through Antimicrobial Stewardship (AMS) Program. There a need to determine factors affect successful implementation an AMS program private hospitals Philippines. This study was conducted identify enablers potential barriers implementing nine (9) hospitals....
In our recent study, we demonstrated that oncogenic RAS (rat sarcoma)-mediated transformation and tumorigenesis are supported by transcriptional induction of a crucial antioxidant component, SLC7A11 (solute carrier family 7 member 11), otherwise known as XCT, gene encoding the cystine/glutamate transporter. Our data highlight this promotes biosynthesis glutathione, in turn allowing transformed cells to mitigate tumorigenesis-linked oxidative stress.
SUMMARY Energetic stress compels cells to evolve adaptive mechanisms maintain homeostasis. Here, we report that the negative regulators of mRNA translation initiation eukaryotic factor 4E binding proteins 1/2 (4EBP1/2) are essential promote survival mammalian and budding yeast under glucose starvation. Functionally, 4EBP1/2 inhibit fatty acid synthesis upon energetic via repression Acetyl-CoA Carboxylase Alpha ( ACACA ) translation, sparing NADPH, intracellular redox balance. This has...
Supplementary Data from Proteomic Screens for Suppressors of Anoikis Identify IL1RAP as a Promising Surface Target in Ewing Sarcoma
Supplementary Data from Proteomic Screens for Suppressors of Anoikis Identify IL1RAP as a Promising Surface Target in Ewing Sarcoma