A5040694877- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Reproductive Biology and Fertility
- Kruppel-like factors research
- Microtubule and mitosis dynamics
- TGF-β signaling in diseases
- Ovarian cancer diagnosis and treatment
- Nuclear Structure and Function
- Cancer-related Molecular Pathways
- Retinoids in leukemia and cellular processes
- interferon and immune responses
- Protein Degradation and Inhibitors
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Caveolin-1 and cellular processes
- Histone Deacetylase Inhibitors Research
Magee-Womens Research Institute
2023-2024
University of Pittsburgh
2023
Tsinghua University
2023
We recently reported that the transcription factor NFATC4, in response to chemotherapy, drives cellular quiescence increase ovarian cancer chemoresistance. The goal of this work was better understand mechanisms NFATC4-driven chemoresistance.We used RNA sequencing identify NFATC4-mediated differential gene expression. CRISPR-Cas9 and FST (follistatin)-neutralizing antibodies were assess impact loss function on cell proliferation ELISA quantify induction patient samples vitro chemotherapy.We...
Abstract Epidermal growth factor EGF-like domain multiple-6 (EGFL6) is highly expressed in high grade serous ovarian cancer (HGSOC) cells and tumor vasculature. EGFL6 acts on to drive cell proliferation migration. To better understand signaling develop therapeutic strategies target HGSOC, we evaluated phosphorylation of putative receptors their downstream signaling. We demonstrated that induced activation ERBB/HER family receptors; treatment led rapid transient EGFR while inducing prolonged...
Abstract Despite advances in immune and targeted therapies, chemotherapy remains the primary treatment for ovarian cancer (OvCa) patients. Unfortunately, most OvCa patients develop chemotherapy-resistant disease that is inevitably fatal. Quiescence an important yet poorly understood mechanism underlying resistance. Therefore, we aimed to characterize quiescent (qOvCa) cells identify novel therapeutic targets improve patient outcomes. Primary patient-derived qOvCa proliferating were isolated...
Abstract Senescent cells have a unique senescence-associated secretory profile (SASP) and understanding SASP has contributed to numerous advances in knowledge on aging cancer biology. Quiescence, which is an important yet poorly understood mechanism for chemoresistance, related but distinct from senescence. Quiescence shares non-proliferative feature with senescence reversible state quiescent can reenter the cell cycle. We hypothesized that, analogous senescent cells, quiescence-associated...
Chemoresistance is a major driver of cancer deaths. One understudied mechanism chemoresistance quiescence. We used single cell culture to identify, retrieve, and RNA-Seq profile primary quiescent ovarian cells (qOvCa). found that many qOvCa differentially expressed genes are transcriptional targets the Myocardin Related Transcription Factor/Serum Response Factor (MRTF/SRF) pathway. also genetic disruption MRTF-SRF interaction, or an MRTF/SRF inhibitor (CCG257081) impact gene expression...
<div>AbstractPurpose:<p>We recently reported that the transcription factor NFATC4, in response to chemotherapy, drives cellular quiescence increase ovarian cancer chemoresistance. The goal of this work was better understand mechanisms NFATC4-driven chemoresistance.</p>Experimental Design:<p>We used RNA sequencing identify NFATC4-mediated differential gene expression. CRISPR-Cas9 and FST (follistatin)-neutralizing antibodies were assess impact loss function on cell...
<div>AbstractPurpose:<p>We recently reported that the transcription factor NFATC4, in response to chemotherapy, drives cellular quiescence increase ovarian cancer chemoresistance. The goal of this work was better understand mechanisms NFATC4-driven chemoresistance.</p>Experimental Design:<p>We used RNA sequencing identify NFATC4-mediated differential gene expression. CRISPR-Cas9 and FST (follistatin)-neutralizing antibodies were assess impact loss function on cell...
<p>Supplementary Figure 4. The effect of ATF2 siRNA on gene expression and PT340 FST induced chemoresistance. A. Schematic detailing the transwell experiments. CellTrace Violet cells were sorted for rapidly dividing (Dim) or quiescent (Bright) which then plated in chambers either as Dim:Dim Bright:Dim. Cells untreated treated with taxol alone combination IgG anti-FST antibody. Cell counts performed dim data was expressed fold chnage. B. Relative PT412 scrambled two independent siRNAs...
<p>Supplementary Table 1. Primers used in this study.</p>
<p>Supplementary Figure 3. The effect of FST or taxol treatment ovarian cancer proliferation and secretion, the ability a neutralization antibody to inhibit FST's on proliferation. A. PT340 PT412 cells were treated with 200 ng/mL for 72h before cell counts performed. B (i) IHC images (ii) FST+ bodies in OVSAHO tumor xenografts without stained both Ki67 (Forangi Blue) (Fast Red). C. Titer anti-FST neutralizing growth.</p>
<p>Supplementary Figure 5. Schematic of FST CRISPR KO guides and in vivo experiment. A. Binding the two commercially available to mediate KO. B. Mice were injected with SKOV3 cells expressing sgRNA #2. then treated 3 times 10mg/kg Taxol intraperitoneal Paclitaxel at days 7, 14 21. C Dissection control mice presenting multiple metastases an FST-KO which showed no residual disease. White arrows point sites disease.</p>
<p>Supplementary Table 1. Primers used in this study.</p>
<p>Supplementary Figure 3. The effect of FST or taxol treatment ovarian cancer proliferation and secretion, the ability a neutralization antibody to inhibit FST's on proliferation. A. PT340 PT412 cells were treated with 200 ng/mL for 72h before cell counts performed. B (i) IHC images (ii) FST+ bodies in OVSAHO tumor xenografts without stained both Ki67 (Forangi Blue) (Fast Red). C. Titer anti-FST neutralizing growth.</p>
<p>Supplementary Figure 5. Schematic of FST CRISPR KO guides and in vivo experiment. A. Binding the two commercially available to mediate KO. B. Mice were injected with SKOV3 cells expressing sgRNA #2. then treated 3 times 10mg/kg Taxol intraperitoneal Paclitaxel at days 7, 14 21. C Dissection control mice presenting multiple metastases an FST-KO which showed no residual disease. White arrows point sites disease.</p>
<p>Supplementary Figure 2. RNA-seq analysis. A. Schematic of the experimental design. B. Waterfall plot data showing 141 genes which were DE at all time points compared to luciferase control in HEY1 and SKOV3 cell lines. C. Unsupervised clustering analysis genes. D. Box plots demonstrating MYC expression following NFATC4 activation. E. STRING genes.</p>
<p>Supplementary Figure 4. The effect of ATF2 siRNA on gene expression and PT340 FST induced chemoresistance. A. Schematic detailing the transwell experiments. CellTrace Violet cells were sorted for rapidly dividing (Dim) or quiescent (Bright) which then plated in chambers either as Dim:Dim Bright:Dim. Cells untreated treated with taxol alone combination IgG anti-FST antibody. Cell counts performed dim data was expressed fold chnage. B. Relative PT412 scrambled two independent siRNAs...
<p>Supplementary Figure 1. Histological analysis of PT340 cell line. cells were injected into NSG mice, and the resulting tumors harvested for histological analysis, H&E staining showed features Clear Cell Ovarian Carcinoma.</p>
<p>Supplementary Figure 1. Histological analysis of PT340 cell line. cells were injected into NSG mice, and the resulting tumors harvested for histological analysis, H&E staining showed features Clear Cell Ovarian Carcinoma.</p>
<p>Supplementary Figure 2. RNA-seq analysis. A. Schematic of the experimental design. B. Waterfall plot data showing 141 genes which were DE at all time points compared to luciferase control in HEY1 and SKOV3 cell lines. C. Unsupervised clustering analysis genes. D. Box plots demonstrating MYC expression following NFATC4 activation. E. STRING genes.</p>
<p>Supplementary Figure 5. Schematic of FST CRISPR KO guides and in vivo experiment. A. Binding the two commercially available to mediate KO. B. Mice were injected with SKOV3 cells expressing sgRNA #2. then treated 3 times 10mg/kg Taxol intraperitoneal Paclitaxel at days 7, 14 21. C Dissection control mice presenting multiple metastases an FST-KO which showed no residual disease. White arrows point sites disease.</p>
<p>Supplementary Figure 3. The effect of FST or taxol treatment ovarian cancer proliferation and secretion, the ability a neutralization antibody to inhibit FST's on proliferation. A. PT340 PT412 cells were treated with 200 ng/mL for 72h before cell counts performed. B (i) IHC images (ii) FST+ bodies in OVSAHO tumor xenografts without stained both Ki67 (Forangi Blue) (Fast Red). C. Titer anti-FST neutralizing growth.</p>
<p>Supplementary Figure 4. The effect of ATF2 siRNA on gene expression and PT340 FST induced chemoresistance. A. Schematic detailing the transwell experiments. CellTrace Violet cells were sorted for rapidly dividing (Dim) or quiescent (Bright) which then plated in chambers either as Dim:Dim Bright:Dim. Cells untreated treated with taxol alone combination IgG anti-FST antibody. Cell counts performed dim data was expressed fold chnage. B. Relative PT412 scrambled two independent siRNAs...
<p>Supplementary Table 1. Primers used in this study.</p>
<p>Supplementary Table 1. Primers used in this study.</p>
<p>Supplementary Figure 5. Schematic of FST CRISPR KO guides and in vivo experiment. A. Binding the two commercially available to mediate KO. B. Mice were injected with SKOV3 cells expressing sgRNA #2. then treated 3 times 10mg/kg Taxol intraperitoneal Paclitaxel at days 7, 14 21. C Dissection control mice presenting multiple metastases an FST-KO which showed no residual disease. White arrows point sites disease.</p>