A5066886590- Epigenetics and DNA Methylation
- Chemical Reactions and Isotopes
- Lung Cancer Treatments and Mutations
- Cancer Cells and Metastasis
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Glycosylation and Glycoproteins Research
- FOXO transcription factor regulation
- Microtubule and mitosis dynamics
- Molecular Biology Techniques and Applications
- Hepatocellular Carcinoma Treatment and Prognosis
- interferon and immune responses
- RNA Research and Splicing
- Prostate Cancer Treatment and Research
- Signaling Pathways in Disease
- Lung Cancer Research Studies
- Genomics and Chromatin Dynamics
- PARP inhibition in cancer therapy
- Cancer Research and Treatments
- Ferroptosis and cancer prognosis
- Galectins and Cancer Biology
- Cancer Immunotherapy and Biomarkers
- Biological Research and Disease Studies
Stanford University
2021-2024
Stratford University
2024
University of Nebraska Medical Center
2015-2021
Nebraska Medical Center
2019
Most cancers are diagnosed in persons over the age of sixty, but little is known about how impacts tumorigenesis. While aging accompanied by mutation accumulation - widely understood to contribute cancer risk it also associated with numerous other cellular and molecular changes likely impact Moreover, incidence decreases oldest part population, suggesting that very old may reduce carcinogenesis. Here we show represses tumor initiation growth genetically engineered mouse models human lung...
ABSTRACT Somatic genome editing in mouse models has increased our understanding of the vivo effects genetic alterations areas ranging from neuroscience to cancer biology and beyond. However, existing are limited their ability create multiple targeted edits. Thus, complex interactions that underlie development, homeostasis, disease remains incomplete. Cas12a is an RNA-guided endonuclease with unique attributes enable simple targeting genes crRNA arrays containing tandem guides. To accelerate...
Abstract Background Several reports have shown the role of glycosylation in pancreatic cancer (PC), but a global systematic screening specific glycosyltransferases (glycoTs) its progression remains unknown. Methods We demonstrate rigorous top-down approach using TCGA-based RNA-Seq analysis, multi-step validation RT-qPCR, immunoblots and immunohistochemistry. identified six unique glycoTs (B3GNT3, B4GALNT3, FUT3, FUT6, GCNT3 MGAT3) PC pathogenesis studied their function CRISPR/Cas9-based KD...
Glycosylation plays a critical role in the aggressiveness of pancreatic cancer (PC). Emerging evidences indicate significant involvement stem cells (CSCs) PC aggressiveness. However, importance glycosylation (PCSCs) is yet to be addressed. Hence, we evaluated potential maintenance stemness PCSCs.Effect specific inhibitors on growth and PCSCs was assessed by MTT assay Side Population (SP) analysis. Isolated PCSCs/SP were characterized using molecular functional assays. Expression...
Cancer stem cells (CSCs), which mediate drug resistance and disease recurrence in several cancers, are therapeutically relevant to ovarian cancer (OC), wherein approximately 80% of patients manifest with tumor recurrence. While there markers for CSCs (OCSCs), the mechanism their self-renewal maintenance by unique driver/markers is poorly understood. Here, we evaluated role hPaf1/PD2, a core component RNA Polymerase II-Associated Factor (PAF) complex, OCSCs through marker functional analyses,...
Abstract Epigenetic dysregulation is widespread in cancer. However, the specific epigenetic regulators and processes they control to drive cancer phenotypes are poorly understood. Here, we employed a novel, scalable high-throughput vivo method perform iterative functional screens of over 250 regulatory genes within autochthonous oncogenic KRAS-driven lung tumors. We identified multiple novel tumor suppressor dependency genes. show that HBO1 complex MLL1 among most impactful suppressive lung....
Pancreatic differentiation 2 (PD2), an important subunit of the human PAF complex, was identified after differential screening analysis 19q13 amplicon, and its overexpression induces oncogenic transformation NIH3T3 cells, hence raising possibility a role for PD2 in tumorigenesis metastasis. To test this hypothesis, we analyzed here functional clinical significance pancreatic ductal adenocarcinoma (PDAC) pathogenesis. Using immunohistochemical analysis, found that is detected acini but not...
Abstract Lung cancer is the leading cause of death worldwide, with lung adenocarcinoma being most common subtype. Many oncogenes and tumor suppressor genes are altered in this type, discovery oncogene mutations has led to development targeted therapies that have improved clinical outcomes. However, a large fraction adenocarcinomas lacks known oncogenes, genesis treatment these oncogene-negative tumors remain enigmatic. Here, we perform iterative vivo functional screens using quantitative...
FACT (facilitates chromatin transcription), an essential and evolutionarily conserved heterodimer from yeast to humans, controls transcription is found be upregulated in various cancers. However, the basis for such upregulation not clearly understood. Our recent results deciphering a new ubiquitin-proteasome system regulation of subunit SPT16 orchestrating hint at involvement proteasome controlling with link cancer. To test this, we carried out experiments human embryonic kidney (HEK293)...
RNA polymerase II-associated factor 1 (PAF1)/pancreatic differentiation 2 (PD2) is a core subunit of the human PAF1 complex (PAF1C) that regulates II function during transcriptional elongation. PAF1/PD2 has also been linked to oncogenesis pancreatic ductal adenocarcinoma (PDAC). Here, we report undergoes posttranslational modification (PTM) through SUMOylation, enhancing radiation resistance PDAC cells. We identified preferentially modified by small ubiquitin-related modifier (SUMO 1), and...
The evolutionarily conserved RNA polymerase II-associated factor 1 (Paf1) from yeast to humans regulates transcription and associated processes, thus, malfunctions and/or misregulations of Paf1 are with cellular pathologies. Indeed, (also known as PD2 or pancreatic differentiation 2) is found be upregulated in poorly differentiated cancer cells, such upregulation involved transformation oncogenesis. However, the basis for these cells remains largely unknown. In light this, we have tested...
Abstract The ability of pancreatic ductal adenocarcinoma (PDAC) cells to form tissue destructive metastases remains a critical impediment therapy. Metastasis is complex multistep process that poorly understood and the molecular events cellular states enable cancer overcome each step metastatic cascade remain elusive. To investigate regulators PDAC metastasis, we accrued characterized panel 31 cell lines generated from mouse models PDAC. Initial experiments indicated these have an ~40-fold...
Abstract Background: RNA polymerase associated factor 1 (PAF1)/Pancreatic differentiation 2 (PD2) is one of the core subunit human PAF1 complex (PAF1C), which regulates various cellular functions such as transcriptional elongation and histone modification. We have previously demonstrated its unique role in oncogenesis stem cell maintenance. Studies that PAF1/PD2 gene yields a protein 59.9 Kda (531 amino acids), however it has been found always gives band at 80 Kda. Further, previous studies...
Abstract Background: Ovarian cancer (OC) is the most lethal gynecological malignancy among women with more than 85% of patients manifesting tumor recurrence. Emerging evidence suggests that a small population cells within - ‘cancer stem (CSCs)’ capable to giving rise entire histopathology and responsible for mediating drug resistance, recurrence, disease aggressiveness. Previously, hPaf1(human RNA polymerase II associated factor1)/PD2 (Pancreatic Differentiation2) core component factor (PAF)...