A5082595926- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cytokine Signaling Pathways and Interactions
- Heat shock proteins research
- DNA Repair Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Redox biology and oxidative stress
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- Organoselenium and organotellurium chemistry
- Sirtuins and Resveratrol in Medicine
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Genetics and Neurodevelopmental Disorders
- Immunotherapy and Immune Responses
- Synthesis and Characterization of Heterocyclic Compounds
- Chronic Myeloid Leukemia Treatments
- Glutathione Transferases and Polymorphisms
- RNA modifications and cancer
- vaccines and immunoinformatics approaches
- Adenosine and Purinergic Signaling
- Microtubule and mitosis dynamics
- Genomic variations and chromosomal abnormalities
- Chromosomal and Genetic Variations
- Epigenetics and DNA Methylation
Osong Medical Innovation Foundation
2016-2024
Baylor College of Medicine
2015-2018
Beijing Proteome Research Center
2018
Augusta University
2010-2016
Georgia Regents Medical Center
2014
The University of Kansas Cancer Center
2010-2012
Augusta University Health
2012
Cancer Research Center
2012
Cancer Center of Kansas
2012
University of Kansas
2012
// Kyungsoo Ha 1 , Warren Fiskus 2,* Dong Soon Choi Srividya Bhaskara 3 Leandro Cerchietti 4 Santhana G. T. Devaraj 2 Bhavin Shah Sunil Sharma Jenny C. Chang Ari M. Melnick Scott Hiebert 5 and Kapil N. Bhalla Georgia Regents University, Augusta, GA Houston Methodist Research Institute, Houston, TX Huntsman Cancer Salt Lake City, UT Weill Cornell Medical College, New York, NY Vanderbilt Nashville, TN * These authors contributed equally to this work Correspondence: Bhalla, email: Keywords :...
DNA methylation is an epigenetic mark critical for regulating transcription, chromatin structure and genome stability. Although many studies have shed light on how impacts transcription interfaces with the histone code, far less known about it regulates We others shown that methyltransferase 1 (DNMT1), maintenance methyltransferase, contributes to cellular response damage, yet DNMT1's exact role in this process remains unclear. particularly form of double-strand breaks (DSBs), poses a major...
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...
SIRT2 is a protein deacetylase with tumor suppressor activity in breast and liver tumors where it mutated; however, the critical substrates mediating its antitumor are not fully defined. Here we demonstrate that binds, deacetylates, inhibits peroxidase of antioxidant peroxiredoxin (Prdx-1) cancer cells. Ectopic overexpression SIRT2, but catalytically dead mutant, increased intracellular levels reactive oxygen species (ROS) induced by hydrogen peroxide, which led to an overoxidized multimeric...
Mammalian cells repair DNA double-strand breaks (DSBs) via efficient pathways of direct, nonhomologous end joining (NHEJ) and homologous recombination (HR). Prior work has identified a complex two polypeptides, PSF p54(nrb), as stimulatory factor in reconstituted vitro NHEJ system. also stimulates early steps HR vitro. p54(nrb) are RNA recognition motif-containing proteins with well-established functions processing transport, their apparent involvement DSB was unexpected. Here we investigate...
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)...
Myosin-binding protein C1 (MYBPC1) is an abundant skeletal muscle that expressed predominantly in slow-twitch fibers. Human MYBPC1 mutations are associated with distal arthrogryposis type 1 and lethal congenital contracture syndrome 4. As function incompletely understood, the mechanism by which human result contractures unknown. Here, we demonstrate using antisense morpholino knockdown, mybpc1 required for embryonic motor activity survival a zebrafish model of arthrogryposis. Mybpc1 morphant...
Abstract The pH-selective interaction between the immunoglobulin G (IgG) fragment crystallizable region (Fc region) and neonatal Fc receptor (FcRn) is critical for prolonging circulating half-lives of IgG molecules through intracellular trafficking recycling. By using directed evolution, we successfully identified mutations that improve pH-dependent binding human FcRn prolong serum persistence a model antibody an Fc-fusion protein. Strikingly, trastuzumab-PFc29 aflibercept-PFc29, therapeutic...
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...
Cdc14 is a phosphatase that controls mitotic exit and cytokinesis in budding yeast. In mammals, the two homologues, Cdc14A Cdc14B, have been proposed to regulate DNA damage repair, whereas rely on another phosphatase, PP2A-B55α. It unclear if Cdc14s work redundantly repair which pathways they participate in. More importantly, their target(s) remains elusive. Here we report Cdc14B knockout (Cdc14B−/−) mouse embryonic fibroblasts (MEFs) showed defects repairing ionizing radiation (IR)-induced...
Abstract Double-strand breaks (DSBs) are repaired through two major pathways, homology-directed recombination (HDR) and non-homologous end joining (NHEJ). While HDR can only occur in S/G2, NHEJ happen all cell cycle phases (except mitosis). How then is the repair choice made S/G2 cells? Here we provide evidence demonstrating that APC Cdh1 plays a critical role choosing pathways cells. Our results suggest default for DSBs to recruit 53BP1 RIF1. BRCA1 blocked from being recruited broken ends...
Coffin–Lowry syndrome (CLS) is a rare X‐linked dominant disorder characterized by intellectual disability, craniofacial abnormalities, short stature, tapering fingers, hypotonia, and skeletal malformations. CLS caused mutations in the Ribosomal Protein S6 Kinase, 90 kDa, Polypeptide 3 ( RPS6KA3 ) gene located at Xp22.12, which encodes Kinase 2 (RSK2). Here we analyzed three unrelated patients including one from historical family found two novel mutations. To date, over 140 have been...
Most histone methyltransferases (HMTase) harbor a predicted Su(var)3–9, Enhancer-of-zeste, Trithorax (SET) domain, which transfers methyl group to lysine residue in their substrates. Mutations of the SET domains were reported cause intellectual disability syndromes such as Sotos, Weaver, or Kabuki syndromes. Sotos syndrome is an overgrowth with caused by haploinsufficiency nuclear receptor binding domain protein 1 (NSD1) gene, HMTase at 5q35.2–35.3. Here, we analyzed NSD1 34 Brazilian...
While computational epitope prediction methods have found broad application, their use, specifically in allergy-related contexts, remains relatively less explored. This study benchmarks several publicly available tools, focusing on the allergenic IgE and T-cell epitopes of Fel d 1, an extensively studied allergen. Using a variety tools accessible via Immune Epitope Database (IEDB) other resources, we evaluate ability to identify known linear 1. Our results show limited effectiveness for...
Double-strand breaks (DSBs) are repaired through two major pathways, homology-directed recombination (HDR) and non-homologous end joining (NHEJ). The choice between these pathways is largely influenced by cell cycle phases. HDR can occur only in S/G2 when sister chromatid provide homologous templates, whereas NHEJ take place all phases of the except mitosis. Central to repair Ku70/80 heterodimer which forms a ring structure that binds DSB ends serves as platform recruit factors involved...