- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nitric Oxide and Endothelin Effects
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Metabolomics and Mass Spectrometry Studies
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- Cytokine Signaling Pathways and Interactions
- Cellular Mechanics and Interactions
- 3D Printing in Biomedical Research
- Cancer-related molecular mechanisms research
- Adenosine and Purinergic Signaling
- RNA Research and Splicing
- Glutathione Transferases and Polymorphisms
- Pleural and Pulmonary Diseases
- Hematological disorders and diagnostics
- Nanofabrication and Lithography Techniques
- S100 Proteins and Annexins
- Angiogenesis and VEGF in Cancer
- Lymphatic System and Diseases
- Molecular Biology Techniques and Applications
- Cell Image Analysis Techniques
University of Michigan
2013-2021
University of Vermont
2013-2020
Michigan United
2019
Abstract Cancer metabolism is rewired to support cell survival in response intrinsic and environmental stressors. Identification of strategies target these adaptions an area active research. We previously described a cytosolic aspartate aminotransaminase (GOT1)-driven pathway pancreatic cancer used maintain redox balance. Here, we sought identify metabolic dependencies following GOT1 inhibition exploit this feature provide additional insight into regulation metabolism. Using pharmacological...
Abstract The Src kinase controls aspects of cell biology and its activity is regulated by intramolecular structural changes induced protein interactions tyrosine phosphorylation. Recent studies indicate that additionally redox-dependent mechanisms, involving oxidative modification(s) cysteines within the protein, although nature molecular-level impact cysteine oxidation are unknown. Using a combination biochemical cell-based studies, we establish critical importance two residues, Cys-185...
Tumor associated macrophages (TAMs) are increasingly recognized as major contributors to the metastatic progression of breast cancer and enriched levels TAMs often correlate with poor prognosis. Despite our current advances, it remains unclear which subset M2-like have highest capacity enhance program mechanisms regulate this process. Effective targeting that aid requires knowledge specific underlying their pro-metastatic actions, avoid anticipated toxicities from generalized macrophages. To...
Abstract Dual oxidase 1 (DUOX1) is an oxidant-generating enzyme within the airway epithelium that participates in innate host defense and epithelial homeostasis. Recent studies indicate DUOX1 suppressed lung cancers by epigenetic silencing, although importance of silencing cancer development or progression unknown. Here we show loss expression a panel cell lines strongly associated with marker E-cadherin. Moreover, RNAi-mediated cells line NCI-H292 was found to result...
Metabolic flux technology with the Seahorse bioanalyzer has emerged as a standard technique in cellular metabolism studies, allowing for simultaneous kinetic measurements of respiration and glycolysis. Methods to extend utility versatility metabolic assay would undoubtedly have immediate wide-reaching impacts. Herein, we describe platform that couples high-content fluorescence imaging simultaneously provide means normalization data cell number; analyze cycle distribution; quantify...
In breast cancer, tumor hypoxia has been linked to poor prognosis and increased metastasis. Hypoxia activates transcriptional programs in cancer cells that lead motility invasion, as well various metabolic changes. One of these changes, an increase glycogen metabolism, further associated with protection from reactive oxygen species damage may premature senescence. Here we report significantly stores response hypoxia. We found knockdown the brain isoform enzyme catalyzes breakdown,...
Abstract Lung cancers are frequently characterized by inappropriate activation of epidermal growth factor receptor (EGFR)-dependent signaling and epigenetic silencing the NADPH oxidase (NOX) enzyme DUOX1, both potentially contributing to worse prognosis. Based on previous findings linking DUOX1 with redox-dependent EGFR activation, present studies were designed evaluate whether in lung may be responsible for altered regulation. In contrast normal epithelial cells, EGF stimulation cancer cell...
Acrolein is a major thiol-reactive component of cigarette smoke (CS) that thought to contribute increased asthma incidence associated with smoking. Here, we explored the effects acute acrolein exposure on innate airway responses two common airborne allergens, house dust mite and Alternaria alternata, observed C57BL/6 mice (5 ppm, 4 h) dramatically inhibited subsequent allergen challenge, demonstrated by attenuated release epithelial-derived cytokines IL-33, IL-25, IL-1α. other...
Innovative cancer treatments, which improve adjuvant therapy and reduce adverse events, are desperately needed. Nanoparticles provide controlled intracellular biomolecule delivery in the absence of activating external cell surface receptors. Prior reports suggest that intracrine signaling, following overexpression basic fibroblast growth factor (FGF-2) after viral transduction, has a toxic effect on diseased cells. Herein, research goals were to (1) encapsulate recombinant FGF-2 within...
Metastases are the leading cause of death in cancer patients. RhoC, a member Rho GTPase family, has been shown to facilitate metastasis aggressive breast cells by influencing motility, invasion, and chemokine secretion, but as yet there is no integrated model precise mechanism how RhoC promotes metastasis. A common phenotypic characteristic metastatic influenced these mechanisms dysregulation cell-cell junctions. Thus, we set out study RhoA- RhoC-GTPase influence junctions cancers. We...
Abstract Non-small cell lung cancer (NSCLC) remains to be one of the leading causes cancer-related mortalities worldwide. The NADPH oxidase homolog, Dual Oxidase 1 (DUOX1), is an H2O2 producing enzyme located in airway epithelium with key roles mucosal host defense and wound repair mechanisms. Recent studies indicate that DUOX1 epigenetically silenced many forms NSCLC via hypermethylation its promoter. We previously demonstrated silencing cells associated epithelial-to-mesenchymal transition...
Abstract The high metastatic potential of inflammatory and other aggressive breast cancer is the major determinant mortality. Recently, it has become clear that signals from tumor microenvironment (TME) harbor capacity to enhance cell dissemination. Of various cells comprise TME, macrophages are most abundant in solid tumors. Therefore, we aimed better understand relationship between macrophage-breast crosstalk. Intriguingly, our previous work showed (IBC) hyper-migratory response macrophage...
Rationale and Objective: Dual oxidase 1 (DUOX1) is an H2O2-generating enzyme within the airway epithelium with functional roles in innate host defense epithelial homeostasis. DUOX1 suppressed lung cancers by epigenetic silencing, although its importance unknown. We used RNAi approaches to investigate impact of silencing on various molecular features cancer. Results: Stable transfection DUOX1-targeted shRNA cancer cell line H292 (H292-shDUOX1) was found result loss characteristics increased...
Abstract Non-small cell lung cancer (NSCLC) remains to be one of the leading causes cancer-related mortalities worldwide. The NADPH oxidase homolog, Dual Oxidase 1 (DUOX1), is an H2O2 producing enzyme located in airway epithelium with key roles mucosal host defense and wound repair mechanisms. Recent studies indicate that DUOX1 epigenetically silenced many forms NSCLC via hypermethylation its promoter. We previously demonstrated silencing cells closely associated epithelial-to-mesenchymal...
Non‐small cell lung cancer (NSCLC) remains to be one of the leading causes cancer‐related mortalities worldwide. The NADPH oxidase homolog, Dual Oxidase 1 (DUOX1), is an H2O2 producing enzyme located in airway epithelium with key roles mucosal host defense and wound repair mechanisms. Recent studies indicate that DUOX1 epigenetically silenced many forms NSCLC via hypermethylation its promoter. We previously demonstrated silencing cells closely associated epithelial‐to‐mesenchymal transition...
Abstract Breast cancer commonly gives rise to lymph node metastases, and it has been suggested that tumor cell migration is facilitated by the generation of new lymphatic vessels, or lymphangiogenesis. Lymphatic endothelial hyaluronic acid receptor 1 (LYVE-1) a (HA) used as vessel marker. LYVE-1 observed in variety breast epithelial cells, its lymphangiogenic function remains unclear. casually linked vascular growth factors VEGF-C VEGF-D, which are well appreciated for their roles responses....
Inflammatory breast cancer (IBC) is an extremely aggressive and rare form of that disproportionally affects African American younger women. While IBC represents 1-5% cancers, it accounts for 10% all deaths annually in the United States. We have previously shown metabolic characteristics IBC, specifically triple negative (TN) inflammatory cell line SUM149, are significantly altered from those normal cells. RhoC, a member Ras superfamily GTPases, contributes to metastatic phenotype acts as...
SUMMARY Metabolic flux technology with the Seahorse bioanalyzer has emerged as a standard technique in cellular metabolism studies, allowing for simultaneous kinetic measurements of respiration and glycolysis. Methods to extend utility versatility metabolic assay would undoubtedly have immediate wide-reaching impacts. Herein, we describe platform that couples high-content fluorescence imaging simultaneously enhance normalization data cell number; analyze cycle progression; quantify...