Chris D. Vulpe
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View article: cellMCD Effectively Discovers Drug Resistance and Sensitivity Genes for Acute Myeloid Leukemia
cellMCD Effectively Discovers Drug Resistance and Sensitivity Genes for Acute Myeloid Leukemia Open
Background: Rapid advances in biotechnology provide researchers with the opportunity to integrate omics profiles (genomics, epigenomics, transcriptomics, proteomics, etc.) with multiple phenotypes or experimental conditions. In cancers suc…
Identification of Functional Genetic Components Modulating Toxicity Response to PFOS using Genome-wide CRISPR Screens in HepG2/C3A cells Open
Perfluorooctane sulfonate (PFOS) poses significant health and environmental risks due to its persistence and widespread use and has been linked to various adverse outcomes, such as liver toxicity. Although the molecular responses and toxic…
Physiologically Relevant 3D CRISPR Screening Enhances Mechanistic Insight into Chemical Toxicity Compared to 2D Screening Open
Many omics-based approaches in toxicology research primarily rely on correlative data, often lacking functional relationships or causal links between genotypes and phenotypes. CRISPR-based approaches can overcome this limitation by establi…
Characterizing common loss-of-function genes and their potential utility in assessing population variability and chemical susceptibility Open
Inter-individual and population variability in susceptibility to chemical exposures confounds determination of threshold exposure levels to protect the most vulnerable. Current risk assessment frameworks, in the absence of empiric chemical…
View article: Parkinson’s disease LRRK2 mutations dysregulate iron homeostasis and promote oxidative stress and ferroptosis in human neurons and astrocytes
Parkinson’s disease LRRK2 mutations dysregulate iron homeostasis and promote oxidative stress and ferroptosis in human neurons and astrocytes Open
Background Iron accumulation is a hallmark of sporadic and familial Parkinson’s disease (PD) pathology and correlates with clinical motor symptom severity. The biochemical mechanisms driving iron dyshomeostasis in PD brain and whether thes…
View article: CerS2 is a druggable target in triple-negative breast cancer
CerS2 is a druggable target in triple-negative breast cancer Open
SUMMARY Triple-negative breast cancer (TNBC) remains a significant clinical challenge due to its aggressive nature and lack of effective targeted therapies. The enzyme ceramide synthase 2 (CerS2), which synthesizes pro-apoptotic very long-…
Novel Lipid Biomarkers of Chronic Kidney Disease of Unknown Etiology Based on Urinary Small Extracellular Vesicles: A Pilot Study of Sugar Cane Workers Open
Background/Objectives: Chronic kidney disease of unknown etiology (CKDu) disproportionately affects young male agricultural workers who are otherwise healthy. There is a scarcity of biomarkers for early detection of this type of kidney dis…
View article: Genome-wide CRISPR/Cas9 screen identifies AraC-daunorubicin-etoposide response modulators associated with outcomes in pediatric AML
Genome-wide CRISPR/Cas9 screen identifies AraC-daunorubicin-etoposide response modulators associated with outcomes in pediatric AML Open
Cytarabine, daunorubicin, and etoposide (ADE) have been the standard backbone of induction chemotherapy regimen for patients with pediatric acute myeloid leukemia (pAML) for >5 decades. However, chemoresistance is still a major concern, an…
Electron microscopy evidence of gadolinium toxicity being mediated through cytoplasmic membrane dysregulation Open
Past functional toxicogenomic studies have indicated that genes relevant to membrane lipid synthesis are important for tolerance to the lanthanides. Moreover, previously reported imaging of patient's brains following administration of gado…
View article: Effects of dietary iron deficiency or overload on bone: Dietary details matter
Effects of dietary iron deficiency or overload on bone: Dietary details matter Open
Thus, these data show that cortical bone is more susceptible to iron overload than trabecular bone and highlight the importance of a nutrient-rich diet to potentially mitigate the negative effects of iron overload on bone.
Assessing inorganic nanoparticle toxicity through omics approaches Open
This review aims to provide a deeper understanding and new perspectives of omics approaches to characterize the toxicity and biological interactions of inorganic nanoparticles, and improve the safety of nanoparticle applications.
View article: CRISPR/Cas9 Screen Identifies CPX-351 and 7+3 Regimens Response Modulators with Distinct Sensitive and Resistant Profiles
CRISPR/Cas9 Screen Identifies CPX-351 and 7+3 Regimens Response Modulators with Distinct Sensitive and Resistant Profiles Open
CPX-351 (dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio) is approved for newly diagnosed high-risk and secondary AML as an alternative to the widely used cytarabine and daunorubicin (7+3) …
View article: YAP at the Crossroads of Biomechanics and Drug Resistance in Human Cancer
YAP at the Crossroads of Biomechanics and Drug Resistance in Human Cancer Open
Biomechanical forces are of fundamental importance in biology, diseases, and medicine. Mechanobiology is an emerging interdisciplinary field that studies how biological mechanisms are regulated by biomechanical forces and how physical prin…
Screening the complex biological behavior of late lanthanides through genome-wide interactions Open
Despite their similar physicochemical properties, recent studies have demonstrated that lanthanides can display different biological behaviors. Hence, the lanthanide series can be divided into three parts, namely early, mid, and late lanth…
View article: The Genetic Architecture of Dietary Iron Overload and Associated Pathology in Mice
The Genetic Architecture of Dietary Iron Overload and Associated Pathology in Mice Open
Tissue iron overload is a frequent pathologic finding in multiple disease states including non-alcoholic fatty liver disease (NAFLD), neurodegenerative disorders, cardiomyopathy, diabetes, and some forms of cancer. The role of iron, as a c…
Data from Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma Open
The HIV-protease inhibitor nelfinavir has shown broad anticancer activity in various preclinical and clinical contexts. In patients with advanced, proteasome inhibitor (PI)–refractory multiple myeloma, nelfinavir-based therapy resulted in …
Supplementary Movie S1C from Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma Open
Cells pre-treated for 3h with 20 µM nelfinavir.
Supplementary Movie S1B from Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma Open
Cells pre-treated for 3h with 10 µM brefeldin A
Supplementary Data from Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma Open
Supplementary Methods, figures and tables
Table S4 from Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma Open
All identified binding partners of nelfinavir across multiple cell lines
Supplementary Movie S1B from Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma Open
Cells pre-treated for 3h with 10 µM brefeldin A
Supplementary Movie S1A from Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma Open
Control cells, treated only with biotin
Supplementary Movie S1A from Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma Open
Control cells, treated only with biotin
Supplementary Data from Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma Open
Supplementary Methods, figures and tables
Supplementary Movie S1C from Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma Open
Cells pre-treated for 3h with 20 µM nelfinavir.
Table S4 from Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma Open
All identified binding partners of nelfinavir across multiple cell lines
Data from Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma Open
The HIV-protease inhibitor nelfinavir has shown broad anticancer activity in various preclinical and clinical contexts. In patients with advanced, proteasome inhibitor (PI)–refractory multiple myeloma, nelfinavir-based therapy resulted in …