- Cancer, Hypoxia, and Metabolism
- DNA Repair Mechanisms
- NF-κB Signaling Pathways
- CRISPR and Genetic Engineering
- Glioma Diagnosis and Treatment
- Diet and metabolism studies
- interferon and immune responses
- Histone Deacetylase Inhibitors Research
- Genomics and Chromatin Dynamics
- PARP inhibition in cancer therapy
- Peroxisome Proliferator-Activated Receptors
- Cell death mechanisms and regulation
- Chronic Myeloid Leukemia Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Amino Acid Enzymes and Metabolism
- Protein Degradation and Inhibitors
- Biofield Effects and Biophysics
- RNA Research and Splicing
- Estrogen and related hormone effects
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Eosinophilic Disorders and Syndromes
- Ion Transport and Channel Regulation
- Cancer Cells and Metastasis
- Sirtuins and Resveratrol in Medicine
The University of Texas MD Anderson Cancer Center
2009-2025
Burdwan Medical College & Hospital
2016-2023
The University of Texas Southwestern Medical Center
2013-2022
Houston Methodist
2014-2022
Methodist Hospital
2008-2018
Cornell University
2016-2018
KPC Medical College and Hospital
2013
Case Western Reserve University
2006-2012
University Hospitals of Cleveland
2012
IST Research
2008-2011
Central nervous system (CNS) is an immune privileged site, nevertheless inflammation associates with many CNS diseases. Peroxisome proliferator‐activated receptors (PPARs) are a family of nuclear hormone that regulate and inflammatory responses. Specific ligands for PPAR α , γ δ isoforms have proven effective in the animal models multiple sclerosis (MS), Alzheimer′s disease, Parkinson′s trauma/stroke, suggesting their use treatment neuroinflammatory The activation NF‐ κ B Jak‐Stat signaling...
Despite the success of imatinib mesylate (IM) in early chronic phase myeloid leukemia (CML), patients are resistant to IM and other kinase inhibitors later stages CML. Our findings indicate that inhibition Janus 2 (Jak2) Bcr-Abl+ cells overcomes resistance although precise mechanism Jak2 action is unknown. Knocking down reduced levels Bcr-Abl protein also phosphorylation Tyr177 Bcr-Abl, overexpression rescued these knockdown effects. Treatment with for 4-6 h but not pTyr177 levels. In vitro...
Alpha actinins (ACTNs) are known for their ability to modulate cytoskeletal organization and cell motility by cross-linking actin filaments. We show here that ACTN4 harbors a functional LXXLL receptor interaction motif, interacts with nuclear receptors in vitro mammalian cells, potently activates transcription mediated receptors. Whereas overexpression of potentiates estrogen α (ERα)-mediated transient transfection reporter assays, knockdown decreases it. In contrast, histone deacetylase 7...
Cell-cycle phase is a critical determinant of the choice between DNA damage repair by nonhomologous end-joining (NHEJ) or homologous recombination (HR). Here, we report that double-strand breaks (DSBs) induce ATM-dependent MOF (a histone H4 acetyl-transferase) phosphorylation (p-T392-MOF) and phosphorylated colocalizes with γ-H2AX, ATM, 53BP1 foci. Mutation site (MOF-T392A) impedes in S G2 but not G1 cells. Expression MOF-T392A also blocks reduction DSB-associated seen wild-type S/G2 cells,...
Promyelocytic leukemia protein (PML) sumoylation has been proposed to control the formation of PML nuclear bodies (NBs) and is crucial for PML-dependent cellular processes, including apoptosis transcriptional regulation. However, regulatory mechanisms its specific roles in NBs remain largely unknown. Here, we show that histone deacetylase 7 (HDAC7) knockdown reduces size number human umbilical vein endothelial cells (HUVECs). HDAC7 coexpression stimulates independent HDAC activity....
The chromatin remodeling factor SMARCAD1, an SWI/SNF ATPase family member, has a role in 5′ end resection at DNA double-strand breaks (DSBs) to produce single-strand (ssDNA), critical step for subsequent checkpoint and repair loading remove damage. However, the mechanistic details of SMARCAD1 coupling damage response pathways remains unknown. Here we report that is recruited DSBs through ATM-dependent process. Depletion reduces ionizing radiation (IR)-induced repairosome foci formation DSB...
Myeloid cell leukemia 1 (MCL-1) is a prosurvival BCL-2 protein family member highly expressed in hematopoietic stem cells (HSCs) and regulated by growth factor signals that manifest antiapoptotic activity. Here we report depletion of MCL-1 but not its isoform MCL-1S increases genomic instability sensitivity to ionizing radiation (IR)-induced death. association with DNA increased postirradiation, the colocalized 53BP1 foci. Postirradiation, MCL-1-depleted exhibited decreased γ-H2AX foci,...
Histone deacetylase 7 (HDAC7) is a member of class IIa HDACs that regulate myocyte enhancer factor-2 (MEF2)-mediated transcription and participate in multiple cellular processes such as T cell apoptosis. We have identified alpha-actinin 1 4 HDAC-interacting proteins. The interaction domains are mapped to C terminus amino acids 72-172 HDAC7. A point mutation HDAC7 disrupts its association with MEF2A also 4, indicating binding sites largely overlap. isolated novel splice variant predominantly...
Brain tumours present unique challenges to conventional therapies and pose major health problems around the world. tumour stem cells (BTSCs) represent a small fraction of that maintain growth, drug resistance recurrence properties. Constitutive androstane receptor (CAR) is nuclear transcription factor regulates metabolism homoeostasis. In this study, we examined effect CAR agonist, 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehydeO-(3,4-dichlorobenzyl)oxime (CITCO) on BTSCs.The...
Abstract The homologous recombination (HR) repair pathway maintains genetic integrity after DNA double-strand break (DSB) damage and is particularly crucial for maintaining fidelity of expressed genes. Histone H4 acetylation on lysine 16 (H4K16ac) associated with transcription, but how pre-existing H4K16ac directly affects DSB not known. To answer this question, we used CRISPR/Cas9 technology to introduce I-SceI sites, or reporter cassettes, at defined locations within gene-rich (high...
Radiation‑induced lung injury (RILI) is a prevalent complication following thoracic radiation, and currently there lack of effective intervention options. The present study investigated the potential Compound Kushen Injection (CKI), botanical drug, to mitigate inflammatory responses in mice with RILI, along its underlying mechanisms action. C3H underwent total irradiation (TLI) intraperitoneal injection CKI (2, 4 or 8 ml/kg) once daily for weeks. Pre‑radiation treatment ml/kg starting 2...
RIP1 is a central mediator of cell death in response to stress but can also mediate survival by activating NF-κB. Here, we show that acts as switch EGFR signaling. EGFRvIII an oncogenic mutant does not bind ligand and coexpressed with EGFRWT glioblastoma multiforme (GBM). recruits ubiquitin ligases RIP1, resulting K63-linked ubiquitination RIP1. binds TAK1 NEMO, forming EGFRvIII-RIP1 signalosome activates essential for EGFRvIII-mediated oncogenicity correlates NF-κB activation GBM....
The nitric oxide (NO)-cyclic GMP pathway contributes to human stem cell differentiation, but NO free radical production can also damage DNA, necessitating a robust DNA response (DDR) ensure survival. How the DDR is affected by differentiation unclear. Differentiation of cells, either inducible pluripotent or embryonic derived, increased residual as determined γ-H2AX and 53BP1 foci, with S-phase-specific chromosomal aberration after exposure DNA-damaging agents, suggesting reduced homologous...
Mutations in α-actinin 4 (ACTN4) are linked to familial forms of focal segmental glomerulosclerosis (FSGS), a kidney disease characterized by proteinuria due podocyte injury. The mechanisms underlying ACTN4 mutant-associated FSGS not completely understood. Although α-actinins better known cross-link actin filaments and modulate cytoskeletal organization, we have previously shown that interacts with transcription factors including estrogen receptor MEF2s potentiates their transcriptional...
Glioblastoma Multiforme (GBM) is the most common glial brain tumor resulting in very low patient survival despite current extensive therapeutic efforts. Emerging evidence suggests that more effective treatments are required to overcome heterogeneity, drug resistance and a complex tumor-supporting microenvironment. PBI-05204 specifically formulated botanical consisting of modified supercritical C02 extract Nerium oleander has undergone both Phase I II clinical trials United States for...
The human MOF (hMOF) protein belongs to the MYST family of histone acetyltransferases and plays a critical role in transcription DNA damage response. is essential for cell proliferation; however, its during replication replicative stress unknown. Here we demonstrate that cells depleted under induced by cisplatin, hydroxyurea, or camptothecin have reduced survival, higher frequency S-phase-specific chromosome damage, increased R-loop formation. depletion decreased fork speed and, when...