A5031392337- Genomics and Chromatin Dynamics
- Renal Diseases and Glomerulopathies
- Cervical Cancer and HPV Research
- DNA Repair Mechanisms
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Reproductive System and Pregnancy
- Estrogen and related hormone effects
- Renal and related cancers
- Histone Deacetylase Inhibitors Research
- Plant Virus Research Studies
- Ubiquitin and proteasome pathways
- Ovarian cancer diagnosis and treatment
- Molecular Biology Techniques and Applications
- Forensic and Genetic Research
- Endometriosis Research and Treatment
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Viral-associated cancers and disorders
- Reproductive tract infections research
- PARP inhibition in cancer therapy
- Ion Transport and Channel Regulation
- Cancer-related molecular mechanisms research
- DNA and Nucleic Acid Chemistry
National Institutes of Health
2015-2024
National Institute of Allergy and Infectious Diseases
2017-2024
National Cancer Institute
2015-2017
Case Western Reserve University
2006-2016
University School
2016
ORCID
2016
University Hospitals of Cleveland
2012
Bhabha Atomic Research Centre
2003-2004
Appropriate DNA double-strand break (DSB) repair factor choice is essential for ensuring accurate outcome and genomic integrity. The factors that regulate this process remain poorly understood. Here, we identify two repressive chromatin components, the macrohistone variant macroH2A1 H3K9 methyltransferase tumor suppressor PRDM2, which together direct between antagonistic DSB mediators BRCA1 53BP1. macroH2A1/PRDM2 module mediates an unexpected shift from accessible to condensed requires...
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...
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...
Glucocorticoids are a general class of steroids that possess renoprotective activity in glomeruli through their interaction with the glucocorticoid receptor. However, mechanisms by which glucocorticoids ameliorate proteinuria and glomerular disease not well understood. In this study, we demonstrated α actinin 4 (ACTN4), an actin-cross-linking protein known to coordinate cytoskeletal organization, interacts receptor (GR) nucleus human podocytes (HPCs), key cell type glomerulus critical for...
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...
We have shown previously that Sp100 (a component of the ND10 nuclear body) represses transcription, replication and establishment incoming human papillomavirus (HPV) DNA in early stages infection. In this follow up study, we show does not substantially regulate viral infection maintenance phase, however at late interacts with amplifying genomes to repress processes. find localizes HPV16 foci generated primary keratinocytes, HPV31 form differentiated cells, CIN 1 cervical biopsies. To analyze...
α-Actinins (ACTNs) are a family of proteins cross-linking actin filaments that maintain cytoskeletal organization and cell motility. Recently, it has also become clear ACTN4 can function in the nucleus. In this report, we found (full length) its spliced isoform (Iso) possess an unusual LXXLL nuclear receptor interacting motif. Both potentiate basal transcription activity directly interact with estrogen α, although binds ERα more strongly. We have both ligand-independent ligand-dependent...
The life cycle of human papillomavirus (HPV) depends on keratinocyte differentiation as the virus modulates and takes advantage cellular pathways to replicate its genome assemble viral particles in differentiated cells. Viral genomes are amplified nuclear replication foci keratinocytes, DNA repair factors from damage response signaling pathway recruited DNA. HPV is associated with histones at all stages infectious cycle, here, we show that histone variant macroH2A1 bound enriched isoforms...
Glomerular podocytes are highly differentiated epithelial cells that key components of the kidney filtration units. Podocyte damage or loss is hallmark nephritic diseases characterized by severe proteinuria. Recent studies implicate hormones including glucocorticoids (ligand for glucocorticoid receptor) and vitamin D3 D protect promote repair from injury. In order to elucidate mechanisms underlying hormone-mediated podocyte-protecting activity injury, we carried out microarray gene...
The macroH2A1.2 histone variant facilitates the response to replication stress with implications for genome maintenance and cell growth. A mutually exclusive splice variant, macroH2A1.1, has opposing effects on DNA repair outcome proliferation. Here we discuss potential impact of splicing-modulated macroH2A1 chromatin organization function malignant transformation.
Nuclear receptors are a family of ligand-activated, DNA sequence-specific transcription factors that regulate various aspects animal development, cell proliferation, differentiation, and homeostasis. The physiological roles nuclear their ligands have been intensively studied in cancer metabolic syndrome. However, role kidney diseases is still evolving, despite being used clinically to treat renal for decades. This review will discuss the progress our understanding physiology with emphasis on...
Human papillomavirus genomes replicate extrachromosomally in infected tissues and derived keratinocyte cells. The cell line CIN12 9E was established from a cervical CIN1 lesion, contains replicating HPV31 genomes, is widely used as model to study the HPV life cycle. Here, we clone sequence genome.
Glomerular podocytes are highly differentiated epithelial cells that key components of the kidney filtration units.Podocyte damage or loss is hallmark nephritic diseases characterized by severe proteinuria.Recent studies implicate hormones including glucocorticoids (ligand for glucocorticoid receptor) and vitamin D3 D protect promote repair from injury.In order to elucidate mechanisms underlying hormone-mediated podocyte-protecting activity injury, we carried out microarray gene expression...
Abstract DNA was extracted by using a non-enzymatic method (1) from blood of normal, healthy, and random individuals. Amplification each the three loci performed locus specific primers PCR conditions were as described Lichter et al. (2) for DRD4 Perez-lezaun (3) STR markers. Forward primer both markets labeled with fluorescent Cy5™dye amidite (Amersham Pharmacia Biotech Pvt.Ltd, Sweden). carried out in 25 µL reaction mixture containing ng genomic Eppendorf Gradient Master Cycler all loci.
Abstract Introduction: Long non-coding RNAs (lncRNAs) have been shown to contribute DNA damage response (DDR) by regulating gene expression. However, very little is known about the role that lncRNAs play in repair. In this study we characterized a lncRNA regulates repair Homologous recombination (HR) modulating recruitment of factors at sites damage. Experimental procedures: Control or treated cells were processed for expression analysis, qPCR, live cell imaging, Immunochemistry, Western...
Glomerular podocytes are highly specialized terminally differentiated cells that function as a filtration barrier in the kidney. Loss or damage to is associated with nephrotic syndromes, including focal segmental glomerulosclerosis (FSGS), chronicle kidney disease characterized by proteinuria. Mutations actin‐crosslinking protein alpha actinin 4 (ACTN4) familial forms of FSGS. ACTNs better known for their ability bind actin filaments and modulate cytoskeletal organization. However, we have...
Alpha actinins (ACTNs) are known for their ability to modulate cytoskeletal organization and cell motility by crosslinking actin filaments. However, recently it has been shown that the ACTNs can also play an important role in transcriptional regulation. ACTN4 mutations including K228E, T232I S235P linked familial focal segmental glomerulosclerosis (FSGS), a kidney disease characterized proteinuria. The mechanisms which these associated with FSGS not well defined. We have demonstrated here...
Histone deacetylase 7 (HDAC7) is a member of class IIa HDACs that regulate MEF2-mediated transcription and participate in multiple cellular processes. We have identified alpha actinin 1 4 as HDAC interacting proteins. The interaction domains are mapped to C-terminus á amino acids 72–172 HDAC7. A point mutation HDAC7 disrupts its association with MEF2A also 4, indicating binding sites largely overlapping. isolated novel splice variant predominantly localized the nucleus, pattern distinct from...