A5023990588- Protein Degradation and Inhibitors
- Chronic Lymphocytic Leukemia Research
- Acute Myeloid Leukemia Research
- Genomics and Phylogenetic Studies
- Lymphoma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Mycobacterium research and diagnosis
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Advanced biosensing and bioanalysis techniques
- Cancer-related gene regulation
- MicroRNA in disease regulation
- Gene expression and cancer classification
- Immunodeficiency and Autoimmune Disorders
- RNA Interference and Gene Delivery
- Chronic Myeloid Leukemia Treatments
- RNA and protein synthesis mechanisms
- CAR-T cell therapy research
- Circular RNAs in diseases
- Cancer therapeutics and mechanisms
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
Eli Lilly (United States)
2022-2024
The Ohio State University
2014-2023
Sivas Cumhuriyet Üniversitesi
2014-2021
The Ohio State University Wexner Medical Center
2011-2017
University of Illinois Hospital & Health Sciences System
2017
University of Illinois Chicago
2017
Ohio University
2016
Antalya Bilim University
2016
Başkent University
2016
Çankırı Karatekin University
2016
Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (BTK) and effective in chronic lymphocytic leukemia (CLL). Resistance to inhibitors resistance associated with BTK inhibition have not been characterized. Although only a small proportion patients had relapse during ibrutinib therapy, understanding mechanisms important. We evaluated relapsed disease identify mutations that may mediate resistance.
Ibrutinib has been approved by the Food and Drug Administration for treatment of patients with untreated chronic lymphocytic leukemia (CLL) since 2016 but not compared chemoimmunotherapy. We conducted a phase 3 trial to evaluate efficacy ibrutinib, either alone or in combination rituximab, relative
Although Aβ peptides are causative agents in Alzheimer's disease (AD), the underlying mechanisms still elusive. We report that Aβ42 induces a translational block by activating AMPK, thereby inhibiting mTOR pathway. This leads to widespread ER stress, which activates JNK3. JNK3 turn phosphorylates APP at T668, facilitating its endocytosis and subsequent processing. In support, pharmacologically blocking translation results significant increase JNK3-dependent manner. Thus, activation, is...
Zinc deficiency (ZD) increases the risk of esophageal squamous cell carcinoma (ESCC). In a rat model, chronic ZD induces an inflammatory gene signature that fuels ESCC development. microRNAs regulate expression and are aberrantly expressed in cancers. Here we investigated whether (23 weeks) also protumorigenic microRNA signature. Using nanoString technology, evaluated profiles esophagus six additional tissues (skin, lung, pancreas, liver, prostate peripheral blood mononuclear cells [PBMC])....
Bromodomain and extra-terminal (BET) family proteins are key regulators of gene expression in cancer. Herein, we utilize BRD4 profiling to identify critical pathways involved pathogenesis chronic lymphocytic leukemia (CLL). is overexpressed CLL enriched proximal genes upregulated or de novo expressed with known functions disease progression. These genes, including members the B-cell receptor (BCR) signaling pathway, provide a rationale for this therapeutic approach new targets alternative...
Thirty patients with chemotherapy-induced anemia were treated recombinant human erythropoietin for 4 weeks. In this dose-escalation study, cohorts of five to eight per dose level. The doses 25, 50, 100, 200, or 300 IU/kg/d given intravenously 5 days each week. Of 30 patients, 15 (50%) had a greater than 10% increase their hemoglobin (Hb) values and considered responders. At the two highest levels, 11 13 (85%) responded. responding mean Hb level increased by 1.7 g/dL from baseline compared an...
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. It a highly heterogeneous disease, and can be divided roughly into indolent progressive stages based on classic clinical markers. Immunoglobin heavy chain variable region (IgVH) mutational status was found to associated with patient survival outcome, biomarkers linked IgVH has been focus in CLL prognosis research field. However, correlated which accurately predict outcome are yet discovered. In this paper, we investigate...
Background Despite its widespread use, there is no consensus on the postoperative management in patients undergoing free flap reconstructions. We report largest study comparing outcomes, morbidity, and cost with head neck cancer flaps who recovered intensive care unit (ICU) versus a “specialty floor” setting. Methods This was retrospective review of surgery for defects over 4‐year period. Patients before certain date went to ICU immediate after non‐ICU Postoperative medical surgical...
BACKGROUND Exome and targeted sequencing studies have identified potential driver mutations for a variety of tumor types. Cutaneous squamous cell carcinoma (cSCC) is one the most highly mutated cancers but typically associated with low rates metastasis high survival rates. Nevertheless, metastatic cSCC significant health threat; up to 8800 individuals die each year this disease. METHODS Because it difficult predict which cSCCs are more likely metastasize, because best authors' knowledge...
SUMOylation of transcription factors and chromatin proteins is in many cases a negative mark that recruits repress gene expression. In this study, we determined the occupancy Small Ubiquitin-like MOdifier (SUMO)-1 on HeLa cells by use affinity purification coupled with next-generation sequencing. We found SUMO-1 localization was dynamic throughout cell cycle. Surprisingly, observed from G1 through late S phase, but not during mitosis, marks just upstream start site most active housekeeping...
Rearrangements of the MLL (ALL1) gene are very common in acute infant and therapy-associated leukemias. The rearrangements underlie generation fusion proteins acting as potent oncogenes. Several most consistently up-regulated targets fusions, MEIS1 , HOXA7, HOXA9, HOXA10 functionally related have been implicated other types Each four genes was knocked down separately human precursor B-cell leukemic line RS4;11 expressing MLL-AF4. mutant control cells were compared for engraftment NOD/SCID...
Abstract Background Exportin 1 (XPO1/CRM1) is a key mediator of nuclear export with relevance to multiple cancers, including chronic lymphocytic leukemia (CLL). Whole exome sequencing has identified hot-spot somatic XPO1 point mutations which we found disrupt highly conserved biophysical interactions in the NES-binding groove, conferring novel cargo-binding abilities and forcing cellular mis-localization critical regulators. However, pathogenic role played by change-in-function CLL not fully...
Abstract Motivation On-target gene knockdown, using siRNA, ideally results from binding fully complementary regions in mRNA transcripts to induce direct cleavage. Off-target siRNA knockdown can occur through several modes, one being a seed-mediated mechanism mimicking miRNA regulation. Seed-mediated off-target effects when the ∼8 nucleotides at 5’ end of guide strand, called seed region, bind 3’ untranslated mRNA, causing reduced translation. Experiments paired with RNA-seq be used detect...
Abstract Although ∼80% of adult patients with cytogenetically normal acute myeloid leukemia (CN-AML) achieve a complete remission (CR), more than half them relapse. Better identification who are likely to relapse can help inform clinical decisions. We performed RNA sequencing on pretreatment samples from 268 adults de novo CN-AML were younger 60 years age and achieved CR after induction treatment standard “7+3” chemotherapy. After filtering for genes whose expressions associated gene...
Significance In this work we report on the previously uncharacterized clinical and biological role for EGFL7 in acute myeloid leukemia (AML). Patients with increased mRNA expression had lower complete remission rates shorter overall event-free survival, demonstrating relevance of cytogenetically normal AML. Our results show that AML blasts are able to synthesize secrete protein, promoting autocrine blast cell growth. Inhibition decreased proliferation induces apoptosis cells. Taken together,...
Neuroendocrine carcinoma (NEC) can be an aggressive disease with locoregional and distant metastasis. We present this article (1) to highlight the typical presentation of NEC in head neck primary sites such as parotid gland, paranasal sinuses, supraglottis (2) discuss prognosis these tumors based on their histologic subtype stage. base our comments findings retrospective review cases 16 adults-10 men 6 women, aged 43 88 years (mean: 65.8)-who had been diagnosed pathologically confirmed neck....
Protein arginine methyltransferase-5 (PRMT5) is overexpressed in aggressive B-cell non-Hodgkin's lymphomas, including mantle cell lymphoma and diffuse large lymphoma, supports constitutive expression of CYCLIN D1 c-MYC. Here, we combined ChIP analysis with next-generation sequencing to identify microRNA (miRNA) genes that are targeted by PRMT5 lines. We identified enrichment histone 3 dimethylation at Arg-8 (H3(Me2)R8) the promoter regions miR33b, miR96, miR503. knockdown de-repressed...
Protein arginine methyltransferase-5 (PRMT5) is overexpressed in aggressive B-cell non-Hodgkin's lymphomas, including mantle cell lymphoma and diffuse large lymphoma, supports constitutive expression of CYCLIN D1 c-MYC. Here, we combined ChIP analysis with next-generation sequencing to identify microRNA (miRNA) genes that are targeted by PRMT5 lines. We identified enrichment histone 3 dimethylation at Arg-8 (H3(Me2)R8) the promoter regions miR33b, miR96, miR503. knockdown de-repressed...
Bromodomain protein BRD4 reads histone acetylation (H3K27ac), an epigenomic mark of transcription enhancers. CCAAT enhancer binding delta (CEBPD) is a factor typically studied in metabolism. While both are potent effectors and potential therapeutic targets, their relationship was previously unknown. Here we investigated interplay vascular smooth muscle cell (SMC) inflammation. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) revealed H3K27ac/BRD4 enrichment at...