A5063877471- Prostate Cancer Treatment and Research
- Ubiquitin and proteasome pathways
- Lung Cancer Research Studies
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Endoplasmic Reticulum Stress and Disease
- Cancer-related Molecular Pathways
- Peptidase Inhibition and Analysis
- Advanced Proteomics Techniques and Applications
- Animal Virus Infections Studies
- Pancreatic function and diabetes
- Cannabis and Cannabinoid Research
- Monoclonal and Polyclonal Antibodies Research
- Nuclear Structure and Function
- PARP inhibition in cancer therapy
- Epigenetics and DNA Methylation
- Mass Spectrometry Techniques and Applications
- Parvovirus B19 Infection Studies
- Receptor Mechanisms and Signaling
- Cancer Research and Treatments
- Influenza Virus Research Studies
- Radiopharmaceutical Chemistry and Applications
- Viral-associated cancers and disorders
- Genomics and Chromatin Dynamics
Fox Chase Cancer Center
2017-2025
Temple University
2019-2024
Center for Personalized Cancer Treatment
2024
University of the West Indies System
2022
Temple University Health System
2019-2020
Altered MAPK signaling frequently occurs in human disease. MEK1 and MEK2 (MEK1/2) are central protein kinases the cascade that phosphorylate ERK1/2 promoting cell growth. MEK1/2 degraders offer a strategy to characterize both kinase-dependent independent functions of MEK1/2. Here, we discovered degradation, but not kinase inhibition, caused subsequent degradation upstream CRAF via cell-intrinsic mechanism. binding CRAF, catalytic activity, was required for stability maturation functional...
Protein phosphorylation is a reversible post-translation modification essential in cell signaling. This study addresses long-standing question as to how the most abundant serine/threonine protein phosphatase 2 (PP2A) holoenzyme, PP2A/B55α, specifically recognizes substrates and presents them enzyme active site. Here, we show PP2A regulatory subunit B55α recruits p107, pRB-related tumor suppressor substrate. Using molecular cellular approaches, identified conserved region 1 (R1, residues...
Genome-Wide Association Studies (GWAS) and subsequent fine-mapping studies (>50) have implicated single nucleotide polymorphisms (SNPs) located at the CCDC170/C6ORF97-ESR1 locus (6q25.1) as being associated with risk of breast cancer. Surprisingly, our analysis using genome-wide differential allele-specific expression (DASE), an indicator for cancer susceptibility, suggested that genetic alterations CCDC170, but not ESR1, account GWAS-associated this locus. Breast cancer-associated CCDC170...
Abstract The PPP2R2A gene encodes the B55α regulatory subunit of PP2A. Here, we report that is hemizygously lost in ~42% prostate adenocarcinomas, correlating with reduced expression, poorer prognosis, and an increased incidence hemizygous loss (>75%) metastatic disease. Of note, homozygous less common (5%) not at later tumor stages. Reduced expression also seen tissue cell lines. Consistent possibility complete detrimental tumors, deletion cells but present reduces proliferation by...
ABSTRACT A large fraction of epigenetically silent heterochromatin is anchored to the nuclear periphery via ‘tethering proteins’ that function bridge and membrane or lamina. We previously identified a human tethering protein, PRR14, binds through an N-terminal domain, but mechanism regulation lamina association remained be investigated. Here we identify evolutionarily conserved PRR14 binding domain (LBD) both necessary sufficient for positioning at show associates dynamically with lamina,...
The Epstein Barr virus (EBV) infects almost 95% of the population worldwide. While typically asymptomatic, EBV latent infection is associated with several malignancies epithelial and lymphoid origin in immunocompromised individuals. In latently infected cells, genome persists as a chromatinized episome that expresses limited set viral genes different patterns, referred to latency types, which coincide varying stages various malignancies. We have previously demonstrated types correlate...
Abstract The Ser/Thr protein phosphatase 2 A (PP2A) regulates the dephosphorylation of many phosphoproteins. Substrate recognition are mediated by B regulatory subunits. Here, we report identification a substrate conserved motif [RK]-V-x-x-[VI]-R in FAM122A, an inhibitor B55α/PP2A. This is necessary for FAM122A binding to B55α, and computational structure prediction suggests motif, which helical, blocks docking same site. In this model, also spatially constrains access occluding catalytic...
Prostate cell lines from diverse backgrounds are important to addressing disparities in prostate cancer (PCa) incidence and mortality rates among Black men. ACRJ-PC28 was developed a transrectal needle biopsy established via inactivation of the CDKN2A locus simultaneous expression human telomerase. Characterization assays included growth curve analysis, immunoblots, IHC, 3D cultures, immunofluorescence imaging, confocal microscopy, flow cytometry, WGS, RNA-Seq. has been passaged more than 40...
The Ser/Thr protein phosphatase 2A (PP2A) is a highly conserved collection of heterotrimeric holoenzymes responsible for the dephosphorylation many regulated phosphoproteins. Substrate recognition and integration regulatory cues are mediated by B subunits that complexed to catalytic subunit (C) scaffold (A). PP2A/B55 substrate recruitment was thought be charge-charge interactions between surface B55α its substrates. Challenging this view, we recently discovered SLiM [ RK ]- V -x-x-[ VI R in...
<title>Abstract</title> Prostate cancer (PCa) is the most common diagnosed in men worldwide and second leading cause of cancer-related deaths US males 2022. also represents highest mortality disparity between non-Hispanic blacks whites. However, there a relatively small number prostate normal cell lines compared to other cancers. To identify molecular basis PCa progression, it important have epithelial (PrEC) as karyotypically possible. Our lab recently developed novel methodology for rapid...
Prostate cancer (PCa) is the most common diagnosed in men worldwide and was second leading cause of cancer-related deaths US males 2022. also represents highest mortality disparity between non-Hispanic blacks whites. However, there a relatively small number prostate normal cell lines compared to other cancers. To identify molecular basis PCa progression, it important have epithelial (PrEC) as karyotypically possible. Our lab recently developed novel methodology for rapid efficient...
Serine/threonine protein phosphatase 2 (PP2A) forms heterotrimeric holoenzymes, where a scaffold subunit bridges the PP2A catalytic to B regulatory subunit, e.g., B55α. The PP2A/B55α holoenzyme plays key roles in signaling and cell-cycle control targeting multiple substrates. Here, we describe semiquantitative approaches determine substrate specificity. Parts I II detail assess PP2A/B55α-mediated dephosphorylation of immobilized peptide variants. III IV methods PP2A/B55α-substrate-binding...
Abstract A large fraction of epigenetically silent heterochromatin is anchored to the nuclear periphery via “tethering proteins” that function bridge and membrane or lamina. We identified previously a human tethering protein, PRR14, binds through an N-terminal domain, but mechanism regulation lamina association remained be investigated. Here we identify centrally located, evolutionarily conserved PRR14 binding domain (LBD) both necessary sufficient for positioning at also show associates...
<div><p>Prostate cancer cell lines from diverse backgrounds are important to addressing disparities in prostate incidence and mortality rates among Black men. ACRJ-PC28 was developed a transrectal needle biopsy established via inactivation of the <i>CDKN2A</i> locus simultaneous expression human telomerase<i>.</i> Characterization assays included growth curve analysis, immunoblots, IHC, three-dimensional cultures, immunofluorescence imaging, confocal...
<p>In these prior attempts, culture conditions such as media, extra-cellular matrices and flasks were varied to determine the optimal for generation of prostate cancer explants.</p>
<p>Supplemental Table 2: A search in the database of global cell repositories ATCC and ECACC revealed that approximately 40% available prostate derived lines were immortalized via an exogenous source.</p>
<p>Cell viability was determined using the MTS assay and OD readings were taken a 409nm. Plots generated in Microsoft Excel each data point represents average of three replicates. Experiments shown are representative two independent experiments.</p>
<p>STR profile of ACRJ-PC28 generated by IDEXX using PC indicates the novelty cell line (A) as senctic was compared to profiles other lines in DSMZ STR database and did not match anv reported here: (B) that cclls were purely humar origin (C) absence mycoplasma intection</p>
<p>IHC staining on ACRJ-PC28 cells compared to positive controls.</p>
<p>Tissue sample was obtained from a transrectal needle biopsy of the prostate gland patient with PSA</p>
<p>Cell viability was determined using the MTS assay and OD readings were taken a 409nm. Plots generated in Microsoft Excel each data point represents average of three replicates. Experiments shown are representative two independent experiments.</p>