- Genetic and Kidney Cyst Diseases
- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Microtubule and mitosis dynamics
- Renal and related cancers
- Protist diversity and phylogeny
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Hedgehog Signaling Pathway Studies
- Neonatal Respiratory Health Research
- 14-3-3 protein interactions
- Bacterial Genetics and Biotechnology
- Reproductive Biology and Fertility
- Epigenetics and DNA Methylation
- Bacteriophages and microbial interactions
- Sperm and Testicular Function
- Genetic Syndromes and Imprinting
- Cystic Fibrosis Research Advances
- Neurogenesis and neuroplasticity mechanisms
- Developmental Biology and Gene Regulation
- Skin and Cellular Biology Research
- Genomics and Chromatin Dynamics
- Congenital heart defects research
- Genomics and Phylogenetic Studies
- Fibroblast Growth Factor Research
Stony Brook University
2014-2024
Stony Brook School
2022
Institut thématique Génétique, génomique et bioinformatique
2014-2015
State University of New York
2008-2015
Pharmac
2008-2009
Howard Hughes Medical Institute
1999-2008
University of Washington
1999-2008
Florida College
2007
University of Florida
2007
National Institute of Genetics
1996-1999
β-Catenin plays a pivotal role in the transcriptional activation of Wnt-responsive genes by binding to TCF/LEF transcription factors. Although it has been suggested that COOH-terminal region β-catenin functions as an domain, mechanisms remain unclear. To screen for potential coactivators bind β-catenin, we used novel yeast two-hybrid system, Ras recruitment system (RRS) detects protein–protein interactions at inner surface plasma membrane. Using this isolated CREB-binding protein (CBP)....
The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates pRB tumor suppressor protein. Cyclin is overexpressed in 20–30% human breast tumors induced both by oncogenes including those for Ras, Neu, Src, β-catenin/lymphoid enhancer factor (LEF)/T cell (TCF) pathway. ankyrin repeat containing serine-threonine protein kinase, integrin-linked kinase (ILK), binds to cytoplasmic domain β1 β3integrin subunits promotes anchorage-independent growth. We show...
Motile multiciliated cells (MCCs) have critical roles in respiratory health and disease are essential for cleaning inhaled pollutants pathogens from airways. Despite their significance human disease, the transcriptional control that governs multiciliogenesis remains poorly understood. Here we identify TP73, a p53 homolog, as governing program airway multiciliogenesis. Mice with TP73 deficiency suffer chronic tract infections due to profound defects ciliogenesis complete loss of mucociliary...
When the brain or spinal cord is injured, glial cells in damaged area undergo complex morphological and physiological changes resulting formation of scar. This scar contains reactive astrocytes, activated microglia, macrophages other myeloid cells, meningeal proliferating oligodendrocyte precursor (OPCs), a dense extracellular matrix. Whether beneficial detrimental to recovery remains controversial. In acute phase recovery, scar-forming astrocytes limit invasion leukocytes macrophages, but...
The oviduct (known as the fallopian tube in humans) is site for fertilization and pre-implantation embryo development. Female steroid hormones, estrogen progesterone, are known to modulate morphology function of cells oviduct. In this review, we focus on actions progesterone secretory, ciliated, muscle cell functions morphologies during fertilization, development, transport humans, laboratory rodents farm animals. We review some aspects oviductal anatomy histology discuss current assisted...
β-Catenin functions in both cell–cell adhesion and as a transcriptional coactivator the canonical Wnt pathway. Nuclear accumulation of β-catenin is hallmark active signaling frequently observed human cancers. Although shuttles out nucleus, molecular mechanisms underlying its translocation remain poorly understood. Chibby (Cby) an evolutionarily conserved molecule that inhibits β-catenin–mediated activation. Here, we identified 14-3-3ε 14-3-3ζ Cby-binding partners using affinity...
Recent studies have unequivocally identified multipotent stem/progenitor cells in mammary glands, offering a tractable model system to unravel genetic and epigenetic regulation of epithelial cell development homeostasis. In this study, we show that Pygo2, member an evolutionarily conserved family plant homeo domain–containing proteins, is expressed embryonic postnatal progenitor cells. Pygo2 deficiency, which achieved by complete or epithelia-specific gene ablation mice, results defective...
Airway multiciliated epithelial cells play crucial roles in the mucosal defense system, but their differentiation process remains poorly understood. Mice lacking basal body component Chibby (Cby) exhibit impaired mucociliary transport caused by defective ciliogenesis, resulting chronic airway infection. In this paper, using primary cultures of mouse tracheal cells, we show that Cby facilitates docking to apical cell membrane through proper formation ciliary vesicles at distal appendage...
ABSTRACTTranscriptional coactivators play a crucial role in gene expression by communicating between regulatory factors and the basal transcription machinery. The coactivator multiprotein bridging factor 1 (MBF1) was originally identified as molecule that connects Drosophila nuclear receptor FTZ-F1 TATA-binding protein (TBP). MBF1 sequence is highly conserved across species fromSaccharomyces cerevisiae to human. Here we provide evidence acquired vitro vivo yeast mediates GCN4-dependent...
Multiprotein bridging factor 1 (MBF1) is a transcriptional cofactor that bridges between the TATA box-binding protein (TBP) and Drosophila melanogaster nuclear hormone receptor FTZ-F1 or its silkworm counterpart BmFTZ-F1. A cDNA clone encoding MBF1 was isolated from Bombyx mori whose sequence predicts basic consisting of 146 amino acids. Bacterially expressed recombinant functional in interactions with TBP positive MBF2. The also makes direct contact through C-terminal region DNA-binding...
SUMMARY: As part of the Bacillus subtilis genome sequencing project, we have determined complete nucleotide sequence a skin element which is located between spoIVCB and spoIIIC. The entire this 48032 bp in length, contains 57 ORFs with putative ribosome-binding sites. Two them correspond to previously sequenced characterized genes, cwIA spoIVCA. Furthermore, seven ORF products identified show interesting similarities known proteins present data banks, including ø105 immunity repressor,...
Tuberous sclerosis complex (TSC) is characterized by the formation of hamartomas in multiple organs resulting from mutations TSC1 or TSC2 gene. Their protein products, hamartin and tuberin, respectively, form a functional that affects cell growth, differentiation, proliferation. Several lines evidence, including renal tumors derived TSC2+/− animals, suggest loss inhibition tuberin associated with up-regulation cyclin D1. As D1 can be regulated through canonical Wnt/β-catenin signaling...
Chibby (Cby) is a conserved component of the Wnt–β-catenin pathway. Cby physically interacts with β-catenin to repress its activation transcription. To elucidate function in vertebrates, we generated Cby−/− mice and found that after 2–3 d weight loss, majority die before or around weaning. All develop rhinitis sinusitis. When challenged Pseudomonas aeruginosa isolates, are unable clear bacteria from nasal cavity. Notably, exhibit complete absence mucociliary transport caused by marked...
New neurons are continually born throughout adulthood in the subventricular zone of lateral ventricle and subgranular dentate gyrus hippocampus. The sequential synaptic integration adult-born has been widely examined rodents, but mechanisms regulating remain largely unknown. primary cilium, a microtubule–based signaling center, plays essential roles vertebrate development, including development central nervous system. We assembly function cilium hippocampal neurons. Strikingly, cilia absent...
Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies. Cby1, the mammalian orthologue of Drosophila Chibby protein, localizes to mature centrioles, is important for ciliogenesis multiciliated airway epithelia mice, antagonizes canonical Wnt signaling via direct regulation β-catenin. We report that deletion mouse Cby1 gene results cystic kidneys, a phenotype common ciliopathies, facilitates formation primary cilia ciliary...
Multiciliated cells of the airways, brain ventricles, and female reproductive tract provide motive force for mucociliary clearance, cerebrospinal fluid circulation, ovum transport. Despite their clear importance to human biology health, molecular mechanisms underlying multiciliated cell differentiation are poorly understood. Prior studies implicate distal appendage/transition fiber protein CEP164 as a central regulator primary ciliogenesis; however, its role in multiciliogenesis remains...
Newly fertilized embryos spend the first few days within oviduct and are transported to uterus, where they implant onto uterine wall. An implantation of embryo before reaching uterus could result in ectopic pregnancy lead maternal death. Estrogen is necessary for transport mammals; however, mechanism involved estrogen-mediated cellular function remains unclear. In this study, we show mouse models that ciliary length beat frequency oviductal epithelial cells regulated through estrogen...
Embryonic stem cell (ESC)-derived cardiomyocytes are anticipated to serve as a useful source for future cell-based cardiovascular disease therapies. Research emphasis is currently focused on determining methods direct the differentiation of ESCs large population with high purity. To this aim, understanding molecular mechanisms that control ESC-to-cardiomyocyte should play critical role in development methodology. The Wnt/beta-catenin signaling pathway has been implicated both embryonic...
Chibby1 (Cby1) is a small, conserved coiled-coil protein that localizes to centrioles/basal bodies and plays crucial role in the formation function of cilia. During early stages ciliogenesis, Cby1 required for efficient recruitment small vesicles at distal end centrioles facilitate basal body docking plasma membrane. Here, we identified family with sequence similarity 92, member A (FAM92A) FAM92B, which harbor predicted lipid-binding BAR domains, as novel Cby1-interacting partners using...