A5028841827- Histone Deacetylase Inhibitors Research
- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer-related gene regulation
- Hematopoietic Stem Cell Transplantation
- Protein Degradation and Inhibitors
- Chronic Myeloid Leukemia Treatments
- Heat shock proteins research
- Ubiquitin and proteasome pathways
- Cytokine Signaling Pathways and Interactions
- DNA Repair Mechanisms
- Lymphoma Diagnosis and Treatment
- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
- Acute Lymphoblastic Leukemia research
- COVID-19 and healthcare impacts
- Cancer-related Molecular Pathways
- CAR-T cell therapy research
- Autophagy in Disease and Therapy
- Genetic factors in colorectal cancer
- Retinoids in leukemia and cellular processes
- Carcinogens and Genotoxicity Assessment
- Glutathione Transferases and Polymorphisms
- Cancer Genomics and Diagnostics
University of Kansas Medical Center
2015-2025
Children's National
2025
University of Kansas
2012-2024
University Medical Center
2024
The University of Kansas Cancer Center
2011-2023
Cancer Research Institute
2014
Moffitt Cancer Center
2010-2012
Cancer Center of Kansas
2012
National Institutes of Health
2012
Augusta University
2008-2010
Nucleophosmin (NPM1) is among the most frequently mutated genes in acute myeloid leukemia (AML). It not known, however, how resulting oncoprotein mutant NPM1 leukemogenic. To reveal cellular machinery which participates cells, we analyzed endogenous protein interactome by mass spectrometry and discovered abundant amounts of master transcription factor driver monocyte lineage differentiation PU.1 (also known as SPI1). Mutant NPM1, aberrantly accumulates cytoplasm, dislocated into cytoplasm...
Abstract Papillary thyroid carcinoma (PTC) demonstrates significantly reduced patient survival with metastatic progression. Tumor progression can be influenced by metabolism, including antioxidant glutathione (GSH). Glutathione peroxidase 4 (GPX4) is a selenoenzyme that uses GSH as co-factor to regulate lipid peroxidation of cell membranes during increased oxidative stress. GPX4 suppression in tumor cells induce ferroptosis. This study aims examine ferroptosis potentially critical pathway...
Histone deacetylase (HDAC) inhibitors (HDI) induce endoplasmic reticulum (ER) stress and apoptosis, while promoting autophagy, which promotes cancer cell survival when apoptosis is compromised. Here, we determined the in vitro vivo activity of combination pan-HDI panobinostat autophagy inhibitor chloroquine against human estrogen/progesterone receptor HER2 (triple)-negative breast (TNBC) cells. Treatment MB-231 SUM159PT cells with disrupted hsp90/histone 6/HSF1/p97 complex, resulting...
Abstract Purpose: We determined the activity of hsp90 inhibitor, and/or Janus-activated kinase 2 (JAK2) tyrosine inhibitor (TKI), against JAK2-V617F–expressing cultured mouse (Ba/F3-JAK2-V617F) and human (HEL92.1.7 UKE-1) or primary CD34+ myeloproliferative neoplasm (MPN) cells. Experimental Design: Following exposure to AUY922 JAK2-TKI TG101209, levels JAK2-V617F, its downstream signaling proteins, as well apoptosis were determined. Results: Treatment with induced proteasomal degradation...
Coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel severe acute syndrome coronavirus 2 (SARS-CoV-2), was declared pandemic in March 2020, and has more than 600,000 deaths United States at time of this report. Hematopoietic stem cell transplantation (HCT) or chimeric antigen receptor T (CAR-T) therapy recipients have higher risk mortality with COVID-19 owing to profound immune dysregulation. In study, we investigated impact SARS-CoV-2 HCT/CAR-T recipients. This...
AbstractThe PRC2 complex protein EZH2 is a histone methyltransferase that known to bind and recruit DNMT1 the DNA modulate methylation. Here, we determined pan-HDAC inhibitor panobinostat (LBH589) treatment depletes levels, disrupts interaction of with EZH2, as well de-represses JunB in human acute leukemia cells. Similar hsp90 17-DMAG, also inhibited chaperone association heat shock 90 which promoted proteasomal degradation EZH2. Unlike decitabine, demethylates promoter DNA, mediated...
Abstract Increased levels of misfolded polypeptides in the endoplasmic reticulum (ER) triggers dissociation glucose-regulated protein 78 (GRP78) from three transmembrane ER-stress mediators, i.e., kinase RNA-like ER (PERK), activating transcription factor-6 (ATF6), and inositol-requiring enzyme 1α, which results adaptive unfolded response (UPR). In present studies, we determined that histone deacetylase-6 (HDAC6) binds deacetylates GRP78. Following treatment with pan-histone deacetylase...
Following DNA damage that results in stalled replication fork, activation of ATR-CHK1 signaling induces the response (DDR) transformed cells. In present studies on human cervical and breast cancer cells, we determined effects hsp90 inhibition levels accumulation damage/repair-associated proteins following exposure to γ-ionizing radiation (IR; 4 Gy). We show with 17-allylamino-demehoxygeldanamycin or novel, nongeldanamycin analogue AUY922 (resorcinylic isoxazole amide; Novartis Pharma)...
We determined the effects of vorinostat (suberoylanalide hydroxamic acid) and/or MK-0457 (VX-680), an Aurora kinase inhibitor on cultured human (HL-60, OCI-AML3, and K562) primary acute myelogenous leukemia (AML) chronic (CML), as well murine pro-B BaF3 cells with ectopic expression unmutated mutant forms Bcr-Abl.Following exposure to vorinostat, apoptosis, loss viability, activity levels Bcr-Abl proteins were determined.Treatment decreased phosphorylation substrates including serine (S)10...
Abstract Purpose: A deregulated epigenome contributes to the transformed phenotype of mantle cell lymphoma (MCL). This involves activity polycomb repressive complex (PRC) 2, containing three core proteins, EZH2, SUZ12, and EED, in which SET domain EZH2 mediates histone methyltransferase activity. We determined effects 3-deazaneplanocin (DZNep), an S-adenosylhomocysteine hydrolase inhibitor, and/or pan-histone deacetylase inhibitor panobinostat (PS) on cultured primary MCL cells. Experimental...
In the present investigation, we report a previously unsuspected function of tumor suppressor protein, APC (adenomatous polyposis coli), in regulation base excision repair (BER). We identified proliferating cell nuclear antigen-interacting protein-like box sequence that binds DNA polymerase β and blocks β-mediated strand-displacement synthesis long patch BER without affecting short BER. further showed colon cancer line expressing wild-type gene was more sensitive to DNA-methylating agent due...
Abstract Purpose: Bortezomib induces unfolded protein response (UPR) and endoplasmic reticulum stress, as well exhibits clinical activity in patients with relapsed refractory mantle cell lymphoma (MCL). Here, we determined the molecular basis of improved vitro vivo combination pan-histone deacetylase inhibitor panobinostat bortezomib against human, cultured, primary MCL cells. Experimental Design: Immunoblot analyses, reverse transcription-PCR, immunofluorescent electron microscopy were used...
The cell cycle comprises sequential events during which a duplicates its genome and divides it into two daughter cells. This process is tightly regulated to ensure that the receives identical copied chromosomal DNA any errors in replication are correctly repaired. Cyclins their enzyme partners, cyclin-dependent kinases (CDKs), critical regulators of G M phase transitions cycle. Mitogenic signals induce formation cyclin/CDK complexes, resulting phosphorylation activation CDKs. Once activated,...