A5066788873- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- PARP inhibition in cancer therapy
- Cancer Genomics and Diagnostics
- Insect Resistance and Genetics
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Genomics, phytochemicals, and oxidative stress
- Genetics and Neurodevelopmental Disorders
- NF-κB Signaling Pathways
- Neurobiology and Insect Physiology Research
- Signaling Pathways in Disease
- Adenosine and Purinergic Signaling
- Multiple Myeloma Research and Treatments
- Insect and Pesticide Research
- Immune Cell Function and Interaction
- Cutaneous lymphoproliferative disorders research
- FOXO transcription factor regulation
- Plant Molecular Biology Research
Atal Bihari Vajpayee Indian Institute of Information Technology and Management
2023
University of Utah
2013-2022
Huntsman Cancer Institute
2014-2022
Vanderbilt University
2008-2013
Vanderbilt University Medical Center
2013
Barwon Health
2012
Cairns Hospital
2012
Alice Springs Hospital
2012
NIHR Surgical Reconstruction and Microbiology Research Centre
2012
University of Tennessee at Knoxville
2006-2008
Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology.To identify mechanisms for cancer resistance in elephants compare cellular response to DNA damage among elephants, healthy controls, cancer-prone patients with Li-Fraumeni syndrome (LFS).A comprehensive survey of necropsy data was performed across 36 mammalian species validate large long-lived organisms, (n = 644). The African Asian elephant genomes were analyzed potential...
Successful DNA replication and packaging of newly synthesized into chromatin are essential to maintain genome integrity. Defects in the template challenge genetic epigenetic inheritance. Unfortunately, tracking damage responses (DDRs), histone deposition, maturation at forks is difficult mammalian cells. Here we describe a technology called iPOND (isolation proteins on nascent DNA) analyze active damaged high resolution. Using this methodology, define timing deposition maturation. Class 1...
The BCL6 transcriptional repressor is required for the development of germinal center (GC) B cells and diffuse large cell lymphomas (DLBCLs). Although can recruit multiple corepressors, its repression mechanism action in normal malignant unknown. We find that cells, mostly functions through two independent mechanisms are collectively essential to GC formation DLBCL, both mediated N-terminal BTB domain. These (1) a unique ternary BCOR-SMRT complex at promoters, with each corepressor binding...
// 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 :...
Histone deacetylase (HDAC) 3, as a cofactor in co-repressor complexes containing silencing mediator for retinoid or thyroid-hormone receptors (SMRT) and nuclear receptor (N-CoR), has been shown to repress gene transcription variety of contexts. Here, we reveal novel role HDAC3 positive regulator IL-1-induced expression. Various experimental approaches involving RNAi-mediated knockdown, conditional deletion small molecule inhibitors indicate the majority human murine genes. This effect was...
Given the fundamental roles of histone deacetylases (HDACs) in regulation DNA repair, replication, transcription and chromatin structure, it is fitting that therapies targeting HDAC activities are now being explored as anti-cancer agents. In fact, two deacetylase inhibitors (HDIs), SAHA Depsipeptide, FDA approved for single-agent treatment refractory cutaneous T cell lymphoma (CTCL). An important target these HDIs, 3 (HDAC3), regulates processes such metabolism, tumorigenesis through...
Histone deacetylase 3 (HDAC3) contributes to the regulation of gene expression, chromatin structure, and genomic stability. Because HDAC3 associates with oncoproteins that drive leukemia lymphoma, we engineered a conditional deletion allele in mice explore physiological roles Hdac3 hematopoiesis. We used Vav-Cre transgenic trigger recombination, which yielded dramatic loss lymphoid cells, hypocellular bone marrow, mild anemia. Phenotypic functional analysis suggested was required for...
While a number of DNA binding transcription factors have been identified that control hematopoietic cell fate decisions, only limited transcriptional corepressors (e.g., the retinoblastoma protein [pRB] and nuclear hormone corepressor [N-CoR]) linked to these functions. Here, we show Mtg16 (myeloid translocation gene on chromosome 16), which is targeted by t(16;21) in acute myeloid leukemia, required for progenitor decisions early proliferation. Inactivation skewed cells toward...
Histone lysine methylation is a dynamic process that plays an important role in regulating chromatin structure and gene expression. Recent studies have identified Jhd2, JmjC domain-containing protein, as H3K4-specific demethylase budding yeast. However, questions regarding the regulation functions of Jhd2 remain unanswered. In this study, we show has intrinsic activity to remove all three states H3K4 vivo can dynamically associate with modulate levels on both active repressed genes at...
Histone deacetylases (HDACs) play a critical role in the maintenance of genome stability. Class I HDACs, histone deacetylase 1 and 2 (Hdac1 Hdac2) are recruited to replication fork by virtue their interactions with machinery. However, functions for Hdac1 Hdac2 (Hdacs1,2) DNA not fully understood.Using genetic knockdown systems novel Hdacs1,2-selective inhibitors, we found that loss Hdacs1,2 leads reduction velocity, an increase stress response culminating damage. These observed defects due...
Abstract Histone H3K4 methylation is connected to gene transcription from yeast humans, but its mechanistic roles in and chromatin dynamics remain poorly understood. We investigated the functions for Set1 Jhd2, sole methyltransferase demethylase, respectively, S. cerevisiae . Here, we show that Jhd2 predominantly co-regulate genome-wide transcription. find combined activities of via contribute positive or negative transcriptional regulation. Providing insights, our data reveal together...
The class I histone deacetylases are essential regulators of cell fate decisions in health and disease. While pan- class-specific HDAC inhibitors available, these drugs do not allow a comprehensive understanding individual function, or the therapeutic potential isoform-specific targeting. To systematically compare impact catalytic functions HDAC1, HDAC2 HDAC3, we generated human HAP1 lines expressing catalytically inactive enzymes. Using this genetic toolbox effect inhibition with effects...
High grade epithelial ovarian cancers are relatively sensitive to DNA damaging platinum-based chemotherapy, suggesting that the dependencies of tumors on damage response pathways can be harnessed for therapeutic purposes. Our goal was determine if mark gamma-H2AX phosphorylation (pH2AX) could used identify suitable cytotoxic histone deacetylase inhibitors (HDACi) cancer treatment. Nineteen chemically diverse HDACi compounds were tested in 7 cell lines. Fluorescent, biochemical and cell-based...
Philadelphia chromosome-positive (Ph+) B-cell precursor acute lymphoblastic leukemia (ALL) expressing BCR-ABL1 oncoprotein is a major subclass of ALL with poor prognosis. BCR-ABL1-expressing leukemic cells are highly dependent on double-strand break (DSB) repair signals for their survival. Here we report that first-in-class HDAC1,2 selective inhibitor and doxorubicin (a hyper-CVAD chemotherapy regimen component) impair DSB networks in Ph+ using common as well distinct mechanisms. The but not...
Gain-of-function mutations in the catalytic site of EZH2 (Enhancer Zeste Homologue 2), is observed about 22% diffuse large B-cell lymphoma (DLBCL) cases. Here we show that selective inhibition histone deacetylase 1,2 (HDAC1,2) activity using a small molecule inhibitor causes cytotoxic or cytostatic effects gain-of-function mutant (EZH2GOF) DLBCL cells. Our results blocking HDAC1,2 increases global H3K27ac without causing concomitant decrease H3K27me3 levels. data shows sufficient to present...
In this thought commentary, I highlight the discoveries made by Seto and colleagues related to HDAC11 obesity. discuss how their reported work fills a gap in HDAC field comment on clinical implications of findings. Overall, selective inhibition could be novel potential therapeutic avenue for both obesity diabesity, diabetes caused Future studies further dissect mechanistic link between metabolic programs will pave way designing mechanism-based combination strategies these two life style diseases.
Histone deacetylase 3 (HDAC3) is the catalytic component of NCoR/SMRT corepressor complexes that mediate actions transcription factors implicated in regulation B-cell development and function. We crossed Hdac3 conditional knockout mice with Mb1-Cre knockin animals to delete early progenitor B cells. The spleens Hdac3F/-Mb1-Cre+/- were virtually devoid mature cells, B220+CD43+ progenitors accumulated within bone marrow. Quantitative deep sequencing Ig heavy chain locus from populations...