A5007303093- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Sarcoma Diagnosis and Treatment
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Molecular Biology Techniques and Applications
- Immunotherapy and Immune Responses
- Biochemical and Molecular Research
- Cancer Genomics and Diagnostics
- Retinoids in leukemia and cellular processes
- PI3K/AKT/mTOR signaling in cancer
- Chemokine receptors and signaling
- HIV/AIDS drug development and treatment
- Ubiquitin and proteasome pathways
- Lymphoma Diagnosis and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Chronic Lymphocytic Leukemia Research
- Histone Deacetylase Inhibitors Research
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Advanced biosensing and bioanalysis techniques
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
University of Minnesota Medical Center
2011-2025
University of Minnesota
2012-2022
Masonic Cancer Center
2006-2020
Médecins Sans Frontières
2001
Abstract Overall survival of patients with osteosarcoma (OS) has improved little in the past three decades, and better models for study are needed. OS is common large dog breeds genetically inducible mice, making disease ideal comparative genomic analyses across species. Understanding level conservation intertumor transcriptional variation species how it associated progression to metastasis will enable us more efficiently develop effective strategies manage improve therapy. In this study,...
Background/Objectives: NRAS mutations are found in approximately 10% of patients with acute myeloid leukemia (AML), nearly half those occurring at codon 12, but little is known about how differing G12 mutants affect cancer cell activity. Methods: A novel bioinformatic technique, differential expression and pathway ranking (DEAPR), was used to identify the most prominent changes terms both individual genes associated pathways when comparing AML THP-1 cells containing an NRASG12D mutation B11...
Abstract Acute myeloid leukemia (AML) can display de novo or acquired resistance to cytosine arabinoside (Ara-C), a primary component of induction chemotherapy. To identify genes capable independently imposing Ara-C resistance, we applied genome-wide CRISPR library human U937 cells and exposed them Ara-C. Interestingly, all drug resistant clones contained guide RNAs for DCK . avoid gene modification, gRNA cDNA was created by the introduction silent mutations. The screening repeated using ,...
Osteosarcoma is the most common primary bone tumor, with metastatic disease responsible for treatment failure and patient death. A forward genetic screen utilizing Sleeping Beauty mutagenesis in mice previously identified potential drivers of osteosarcoma metastasis, including Slit-Robo GTPase-Activating Protein 2 (Srgap2). This study evaluates role SRGAP2 metastases-associated properties cell lines through Srgap2 knockout via CRISPR/Cas9 nuclease system conditional overexpression murine K12...
Abstract Osteosarcomas are characterized by highly disrupted genomes. Although osteosarcomas lack common fusions, we find evidence of many tumour specific gene-gene fusion transcripts, likely due to chromosomal rearrangements and expression transcription-induced chimeras. Most the fusions result in out-of-frame potentially capable producing long novel protein sequences a plethora neoantigens. To identify explored RNA-sequencing data obtain detailed knowledge transcribed creating program...
Abstract Purpose: Advances in immunotherapy have revolutionized care for some patients with cancer. However, current checkpoint inhibitors are associated significant toxicity and yield poor responses central nervous system tumors, calling into question whether cancer can be applied to glioblastoma multiforme. We determined that targeting the CD200 activation receptors (CD200AR) of a peptide inhibitor (CD200AR-L) overcomes tumor-induced immunosuppression. shown clinical efficacy CD200AR-L...
The use of CRISPR to knockdown or knockout genes is a powerful tool for understanding the specific role gene in disease development. However, it can cause many unanticipated changes transcriptome that are not detected by DNA amplification and Sanger sequencing target site. Various RNA-sequencing techniques be used identify these effectively gauge full impact knockout, thereby providing means selecting appropriate clones further experimentation. Background/Objectives: RNA-seq data from 4...
The evolution from microarrays to transcriptome deep-sequencing (RNA-seq) and RNA interference gene knockouts using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) Transcription Activator-Like Effector Nucleases (TALENs) has provided a new experimental partnership for identifying quantifying the effects of changes on drug resistance. Here we describe results derived two cytarabine (Ara-C) resistance acute myeloid leukemia (AML) cell lines present CRISPR TALEN based...
Follicular lymphoma and diffuse large B-cell (DLBCL) are the most common non-Hodgkin lymphomas distinguishable by unique mutations, chromosomal rearrangements, gene expression patterns. Here, it is demonstrated that early progenitors express 2',3'-cyclic-nucleotide 3' phosphodiesterase (CNP) when targeted with
We previously identified ZNF217 as an oncogenic driver of a subset osteosarcomas using the Sleeping Beauty (SB) transposon system. Here, we followed up by investigating genetic role in osteosarcoma initiation and progression through establishment novel genetically engineered mouse model, vitro assays, orthotopic studies, paired these findings with preclinical studies small-molecule inhibitor. Throughout, demonstrate that is coupled to numerous facets transformation, including proliferation,...
Wnt signaling is activated in many cancer types, yet targeting the canonical pathway has been challenging for therapy. The might be effectively targeted at levels depending on mechanism by which it become hyperactive. Recently, mouse genetic screens have found that R-spondins (RSPOs) act as oncogenes. Evidence includes recurrent genomic rearrangements led to increased
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive, genomically complex, have soft tissue sarcomas, and derived from the Schwann cell lineage. Patients with neurofibromatosis type 1 syndrome (NF1), an autosomal dominant tumor predisposition syndrome, at a high risk for MPNSTs, which usually develop pre-existing benign called plexiform neurofibromas. NF1 is characterized by loss-of-function mutations in gene, encode neurofibromin, Ras GTPase activating protein (GAP)...
Abstract NRAS proteins are central regulators of proliferation, survival, and self-renewal in leukemia. Previous work demonstrated that the effects oncogenic mediating proliferation mutually exclusive within leukemia subpopulations levels vary between highly proliferative self-renewing subpopulations. These findings suggest activity may be important determinants leukemic behavior. To define how affect these functions, we genetically engineered an acute myeloid (AML) cell line, THP-1, to...
Pain is a hallmark feature of sickle cell disease (SCD). Recurrent and unpredictable acute pain due to vaso-oclussive crises (VOC) unique SCD; can be superimposed on chronic pain. To examine the mechanisms underlying in SCD, we performed RNA sequencing dorsal root ganglion (DRG) transgenic mice their age-matched control expressing normal human hemoglobin A, at 2 5 months age. Sickle both ages were equally divided into hypoxia/reoxygenation (to simulate VOC) normoxia treatment, resulting...
Little is known about the prevalence of sexually transmitted infections (STIs) and sexual reproductive health in Central Eastern Europe. However, it clear that major epidemics STIs currently exist.To provide baseline information for development national guidelines on management Azerbaijan.A study STIs, including a questionnaire health, two regions Azerbaijan targeted three groups: (1) pregnant women, (2) gynecology patients, (3) men attending dermatovenereology clinic.The 407 women this had...
Abstract Motivation: Cancer researchers seeking immunotherapy targets in cancer cells need tools to locate highly expressed proteins unique cells. Missense mutation and frameshift location reporter (MMuFLR), a Galaxy-based workflow, analyzes next-generation sequencing paired read RNA-seq output reliably identify small mutations missense protein-coding genes. MMuFLR ignores known SNPs, low quality reads poly-A/T sequences. For each identified, provides the sequence of amino acid substitutions...
<div>Abstract<p>NRAS proteins are central regulators of proliferation, survival, and self-renewal in leukemia. Previous work demonstrated that the effects oncogenic NRAS mediating proliferation mutually exclusive within leukemia subpopulations levels vary between highly proliferative self-renewing subpopulations. These findings suggest activity may be important determinants leukemic behavior. To define how affect these functions, we genetically engineered an acute myeloid (AML)...
Abstract Purpose Advances in immunotherapy have revolutionized care for some cancer patients. However, current checkpoint inhibitors are associated with significant toxicity and yield poor responses patients central nervous system tumors, calling into question whether can be applied to glioblastoma multiforme. We determined that targeting the CD200 activation receptors (CD200AR) of a peptide inhibitor overcomes tumor-induced immunosuppression. shown clinical efficacy trial companion dogs...
SUMMARY Glioblastoma remains a deadly cancer driven by invasion of tumor cells into the brain. Transcriptomic analyses have revealed distinct molecular subtypes, but mechanistic differences that explain clinical are not clear. Here, we show that, as predicted motor-clutch model for cell migration, mesenchymal glioma more spread, generate larger traction forces, and migrate faster in brain tissue compared to proneural cells. Despite their fast migration comparable proliferation rate vitro,...