A5042802136- Immune Response and Inflammation
- Immune cells in cancer
- interferon and immune responses
- Autophagy in Disease and Therapy
- Calcium signaling and nucleotide metabolism
- Pneumocystis jirovecii pneumonia detection and treatment
- Protein Degradation and Inhibitors
- Acute Myeloid Leukemia Research
- Phagocytosis and Immune Regulation
- Sphingolipid Metabolism and Signaling
- Cancer-related gene regulation
- Synthesis and Catalytic Reactions
- Inflammasome and immune disorders
- Cell death mechanisms and regulation
- Lysosomal Storage Disorders Research
- Bioactive Compounds and Antitumor Agents
- Prostate Cancer Treatment and Research
- Synthesis and biological activity
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
University of Pennsylvania
2021-2024
Sidney Kimmel Cancer Center
2022-2023
Thomas Jefferson University
2022-2023
Lysosomal inhibition elicited by palmitoyl-protein thioesterase 1 (PPT1) inhibitors such as DC661 can produce cell death, but the mechanism for this is not completely understood. Programmed death pathways (autophagy, apoptosis, necroptosis, ferroptosis, and pyroptosis) were required to achieve cytotoxic effect of DC661. Inhibition cathepsins, or iron calcium chelation, did rescue DC661-induced cytotoxicity. PPT1 induced lysosomal lipid peroxidation (LLP), which led membrane permeabilization...
Lysosomal autophagy inhibition (LAI) with hydroxychloroquine or DC661 can enhance cancer therapy, but tumor regrowth is common. To elucidate LAI resistance, proteomics and immunoblotting demonstrated that induced lipid metabolism enzymes in multiple cell lines. Lipidomics showed increased cholesterol, sphingolipids, glycosphingolipids. These changes were associated striking levels of GM1+ membrane microdomains (GMM) plasma membranes lysosomes. Inhibition cholesterol/sphingolipid proteins...
Abstract Purpose: DNMT3A mutations confer a poor prognosis in acute myeloid leukemia (AML), but the molecular mechanisms downstream of disease pathogenesis are not completely understood, limiting targeted therapeutic options. The role miRNA DNMT3A-mutant AML is understudied. Experimental Design: DNA methylation and expression was evaluated human patient samples Dnmt3a/Flt3-mutant mice. treatment efficacy TLR7/8-directed therapies on were vitro Results: miR-196b hypomethylated overexpressed...
Macroautophagy/autophagy-lysosome function promotes growth and survival of cancer cells, making them attractive targets for therapy. One intriguing lysosomal target is PPT1 (palmitoyl-protein thioesterase 1). inhibitors derived from chloroquine block autophagy, have significant antitumor activity in preclinical models are being developed clinical trials. However, the role tumorigenesis remains poorly understood. Here we report that melanoma acute siRNA or pharmacological inhibition led to...
<div>AbstractPurpose:<p><i>DNMT3A</i> mutations confer a poor prognosis in acute myeloid leukemia (AML), but the molecular mechanisms downstream of <i>DNMT3A</i> disease pathogenesis are not completely understood, limiting targeted therapeutic options. The role miRNA <i>DNMT3A</i>-mutant AML is understudied.</p>Experimental Design:<p>DNA methylation and expression was evaluated human patient samples...
Supplementary Data from miR-196b–TLR7/8 Signaling Axis Regulates Innate Immune and Myeloid Maturation in <i>DNMT3A</i>-Mutant AML
Supplementary Data from miR-196b–TLR7/8 Signaling Axis Regulates Innate Immune and Myeloid Maturation in <i>DNMT3A</i>-Mutant AML
<div>AbstractPurpose:<p><i>DNMT3A</i> mutations confer a poor prognosis in acute myeloid leukemia (AML), but the molecular mechanisms downstream of <i>DNMT3A</i> disease pathogenesis are not completely understood, limiting targeted therapeutic options. The role miRNA <i>DNMT3A</i>-mutant AML is understudied.</p>Experimental Design:<p>DNA methylation and expression was evaluated human patient samples...
<div>Abstract<p>Lysosomal autophagy inhibition (LAI) with hydroxychloroquine or DC661 can enhance cancer therapy, but tumor regrowth is common. To elucidate LAI resistance, proteomics and immunoblotting demonstrated that induced lipid metabolism enzymes in multiple cell lines. Lipidomics showed increased cholesterol, sphingolipids, glycosphingolipids. These changes were associated striking levels of GM1<sup>+</sup> membrane microdomains (GMM) plasma membranes...
<div>Abstract<p>Lysosomal autophagy inhibition (LAI) with hydroxychloroquine or DC661 can enhance cancer therapy, but tumor regrowth is common. To elucidate LAI resistance, proteomics and immunoblotting demonstrated that induced lipid metabolism enzymes in multiple cell lines. Lipidomics showed increased cholesterol, sphingolipids, glycosphingolipids. These changes were associated striking levels of GM1<sup>+</sup> membrane microdomains (GMM) plasma membranes...
<p>Supplemental Figure S1: LAI remodels the lipidome of melanoma cells. Supplemental S2: induces UGCG, and UGCG inhibition augments DC661 cytotoxicity, this effect is not seen by blocking cholesterol synthesis key earlier steps autophagy. S3: increases formation GMM in cancer S4: synergistically induced cytotoxicity abrogates without elevating ceramide levels. S5: UGCG-associated PDX cells, a combination eliglustat impairs tumor growth therapy-resistant model.</p>
<p>Supplemental Table S1: Patient Characteristics by UGCG expression defined Risk Groups in the Learning Dataset; Supplemental S2: Validation Dataset (Cirenajwis et al., 2015)</p>
<p>Supplemental Table S1: Patient Characteristics by UGCG expression defined Risk Groups in the Learning Dataset; Supplemental S2: Validation Dataset (Cirenajwis et al., 2015)</p>
<p>Supplemental Figure S1: LAI remodels the lipidome of melanoma cells. Supplemental S2: induces UGCG, and UGCG inhibition augments DC661 cytotoxicity, this effect is not seen by blocking cholesterol synthesis key earlier steps autophagy. S3: increases formation GMM in cancer S4: synergistically induced cytotoxicity abrogates without elevating ceramide levels. S5: UGCG-associated PDX cells, a combination eliglustat impairs tumor growth therapy-resistant model.</p>