A5047923526- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- PARP inhibition in cancer therapy
- Cancer Treatment and Pharmacology
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Bioinformatics and Genomic Networks
- Breast Cancer Treatment Studies
- Hippo pathway signaling and YAP/TAZ
- Pluripotent Stem Cells Research
- Cancer Research and Treatments
- Machine Learning in Bioinformatics
- Advanced Fluorescence Microscopy Techniques
- Advanced biosensing and bioanalysis techniques
- Chemokine receptors and signaling
- Signaling Pathways in Disease
- Mechanisms of cancer metastasis
- Computational Drug Discovery Methods
- Gene expression and cancer classification
- Cell Image Analysis Techniques
- Ethics and Legal Issues in Pediatric Healthcare
- Genomics and Chromatin Dynamics
- Neuroblastoma Research and Treatments
- Genital Health and Disease
Georgetown University
2019-2023
Cornell University
2016-2023
Georgetown University Medical Center
2019-2023
Northwestern University
2014
Background:PIM1 kinase is coexpressed with c-MYC in human prostate cancers (PCs) and dramatically enhances c-MYC-induced tumorigenicity. Here we examine the effects of a novel oral PIM inhibitor, AZD1208, on tumorigenesis recurrence.
Abstract AIB1Δ4 is an N-terminally truncated isoform of the oncogene amplified in breast cancer 1 (AIB1) with increased expression high-grade human ductal carcinoma situ (DCIS). However, role DCIS malignant progression has not been defined. Here we CRISPR-engineered RNA splice junctions to produce normal and early-stage epithelial cells that expressed only AIB1Δ4. These showed enhanced motility invasion 3D cell culture. In zebrafish, AIB1Δ4-expressing enabled parental when present a mixed...
CDK4/6 inhibitors are used in the treatment of advanced estrogen receptor (ER)(+) breast cancer. Their efficacy ER(-) and early-stage cancer is currently under investigation. Here, we show that palbociclib, a inhibitor, can inhibit both progression ductal carcinoma situ (DCIS) growth invasive disease an basal model (MCFDCIS) ER(+) luminal (MCF7 intraductal injection). In MCFDCIS cells, palbociclib repressed cell-cycle gene expression, inhibited proliferation, induced senescence, normalized...
<p>A) Sequence alignment of PCR amplicons genomic DNA spanning exon 4 AIB1 (UCSC genome browser). Black filled boxes are the sequences that align to and dotted lines represent missing/deleted sequences. in DCIS-Î"4 cell line is missing part intron 3 4. Two deleted regions around were identified 10A-Î"4 line; both acceptor site. B) Sanger sequencing exons 2, 3, 4, 5 splice junctions. C) mRNA between 2 MCFDCIS-Î"4 clones parental MCFDCIS cells. D) Western blot shows isoforms' protein...
<p>A list of AIB1Î"4 signature genes that were used to generate KM-plots in Figure S5.</p>
<p>A) Quantification of the number Zebrafish embryos with DCIS or DCIS-Î"4-hy cells that have extravasated out blood vessels and into neighboring tissue. p=0.57. B) MCF10A, MCF10A-Î"4 mixed In cell population, only MCF10A parental line was fluorescently labeled scored for extravasation. are at a 4:1 ratio. C) Invasion assay an endothelial monolayer (HUVEC) using ECIS. MCFDCIS were treated conditioned media (CM) from MCFDCIS-Î"4 4 hours before added to monolayer, vice versa. No as...
<div>Abstract<p>AIB1Δ4 is an N-terminally truncated isoform of the oncogene amplified in breast cancer 1 (AIB1) with increased expression high-grade human ductal carcinoma <i>in situ</i> (DCIS). However, role AIB1Δ4 DCIS malignant progression has not been defined. Here we CRISPR-engineered RNA splice junctions to produce normal and early-stage epithelial cells that expressed only AIB1Δ4. These showed enhanced motility invasion 3D cell culture. In zebrafish,...
<p>Supplementary Methods</p>
<p>A) Representative images of hematoxylin and eosin (H&E) staining MCFDCIS, MCFDCIS-Î"4 mixed (4:1 respectively) tumors that were injected in the mammary fat pad SCID/Beige mice after two or five weeks. not collected at weeks due to small tumor size. Scale bar=50μm. B) Growth subcutaneous DCIS DCIS-Î"4-hy athymic nude mice. n=5. **p<0.01. H&E histology 3 bar = 50μm. C) Quantification P63 Luciferase (unique DCIS) co-localization 2 5 ROI= 2007x1500um. D) quantification p63...
<p>A) Principal component analyses of RNA-Seq from MCFDCIS and MCF10A cell lines the AIB1Î"4 corresponding clones. B) Relapse free survival overall KM-plots in patients with ER-negative breast tumors separated by top regulated genes cells. signature gene list used to generate is Supplementary table S3. C) Volcano plots illustrating differentially expressed (DEGs) clones (|log2(FC)|>1.5 -log(adj p-val)>1.3). Full DEGs S1. D) Significantly enriched hallmark pathways set enrichment...
<p>A) FDR-corrected shared and unique ChIP peaks of AIB1 AIB1Î"4 in MCF10A parental cell line (10A) versus AIB1Î"4-expressing isogenic (10A-Î"4). Shared have at least 1bp overlap. B) MCF7 cells treated for 3 hours with estradiol (E2) or vehicle (V) overlapped MCFDCIS (parental derivative lines). data set obtained from Zwart et al(32). C) Motifs within 200 bp the peak summit significant ChIP-Seq were analyzed motif enrichment using HOMER. In red are motifs to cells. D) histone...
<p>A list of enriched pathways using Gene Set Enrichment Analysis (GSEA).</p>
<p>A list of differentially expressed genes in tumors and cells.</p>
<p>A) Principal component analyses of RNA-Seq from MCFDCIS and MCF10A cell lines the AIB1Î"4 corresponding clones. B) Relapse free survival overall KM-plots in patients with ER-negative breast tumors separated by top regulated genes cells. signature gene list used to generate is Supplementary table S3. C) Volcano plots illustrating differentially expressed (DEGs) clones (|log2(FC)|>1.5 -log(adj p-val)>1.3). Full DEGs S1. D) Significantly enriched hallmark pathways set enrichment...
<p>A) Sequence alignment of PCR amplicons genomic DNA spanning exon 4 AIB1 (UCSC genome browser). Black filled boxes are the sequences that align to and dotted lines represent missing/deleted sequences. in DCIS-Î"4 cell line is missing part intron 3 4. Two deleted regions around were identified 10A-Î"4 line; both acceptor site. B) Sanger sequencing exons 2, 3, 4, 5 splice junctions. C) mRNA between 2 MCFDCIS-Î"4 clones parental MCFDCIS cells. D) Western blot shows isoforms' protein...
<p>A list of enriched pathways using Gene Set Enrichment Analysis (GSEA).</p>
<p>A list of differentially expressed genes in tumors and cells.</p>
<p>Supplementary Methods</p>
<p>A) Quantification of the number Zebrafish embryos with DCIS or DCIS-Î"4-hy cells that have extravasated out blood vessels and into neighboring tissue. p=0.57. B) MCF10A, MCF10A-Î"4 mixed In cell population, only MCF10A parental line was fluorescently labeled scored for extravasation. are at a 4:1 ratio. C) Invasion assay an endothelial monolayer (HUVEC) using ECIS. MCFDCIS were treated conditioned media (CM) from MCFDCIS-Î"4 4 hours before added to monolayer, vice versa. No as...
<p>A) FDR-corrected shared and unique ChIP peaks of AIB1 AIB1Î"4 in MCF10A parental cell line (10A) versus AIB1Î"4-expressing isogenic (10A-Î"4). Shared have at least 1bp overlap. B) MCF7 cells treated for 3 hours with estradiol (E2) or vehicle (V) overlapped MCFDCIS (parental derivative lines). data set obtained from Zwart et al(32). C) Motifs within 200 bp the peak summit significant ChIP-Seq were analyzed motif enrichment using HOMER. In red are motifs to cells. D) histone...
<p>A list of AIB1Î"4 signature genes that were used to generate KM-plots in Figure S5.</p>
<p>A) Representative images of hematoxylin and eosin (H&E) staining MCFDCIS, MCFDCIS-Î"4 mixed (4:1 respectively) tumors that were injected in the mammary fat pad SCID/Beige mice after two or five weeks. not collected at weeks due to small tumor size. Scale bar=50μm. B) Growth subcutaneous DCIS DCIS-Î"4-hy athymic nude mice. n=5. **p<0.01. H&E histology 3 bar = 50μm. C) Quantification P63 Luciferase (unique DCIS) co-localization 2 5 ROI= 2007x1500um. D) quantification p63...