A5086540524- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- RNA Research and Splicing
- Reproductive System and Pregnancy
- Protein Kinase Regulation and GTPase Signaling
- Cellular Mechanics and Interactions
- Neuroinflammation and Neurodegeneration Mechanisms
- Cellular transport and secretion
- Reproductive Physiology in Livestock
- Uterine Myomas and Treatments
- Cell Image Analysis Techniques
- Pregnancy and preeclampsia studies
- Cell Adhesion Molecules Research
- Genomics and Chromatin Dynamics
- Neuropeptides and Animal Physiology
- Cardiomyopathy and Myosin Studies
- Cholinesterase and Neurodegenerative Diseases
- Endometriosis Research and Treatment
- Cell death mechanisms and regulation
- Protein Structure and Dynamics
- Cancer-related Molecular Pathways
- Neuroscience and Neural Engineering
- Pain Mechanisms and Treatments
- Nitric Oxide and Endothelin Effects
University at Buffalo, State University of New York
2012-2024
University of Illinois Chicago
2005-2011
Laboratório Bacchi
2008
Indo-American Center
2008
Czech Academy of Sciences
2001-2004
Czech Academy of Sciences, Institute of Physiology
2001-2004
Charles University
2002
Previous short-term studies have correlated an increase in the phosphorylation of 20-kDa light chain myosin II (MLC20) with blebbing apoptotic cells. We found that this MLC20 is rapidly followed by dephosphorylation when cells are stimulated various agents. not a consequence apoptosis because precedes caspase activation proapoptotic agent or kinase (MLCK) inhibited pharmacologically microinjecting inhibitory antibody to MLCK. Moreover, blocking increased cell survival MLCK treated tumor...
Abstract In vertebrates, two myosin Ic isoforms that localize to the cytoplasm and nucleus have been characterized. The isoform predominantly localizes is called nuclear I (NMI). NMI has identified as a key factor involved in processes such transcription by RNA polymerases II intranuclear transport processes. We report here identification of previously uncharacterized third MYOIC gene product A. Similar NMI, this contains unique N‐terminal peptide sequence, colocalizes with polymerase II....
Cholinergic neuronal loss is one of the hallmarks AD related neurodegeneration; however, preclinical promise α7 nAChR drugs failed to translate into humans. CHRFAM7A, a uniquely human fusion gene, negative regulator and was unaccounted for in models.Molecular methods: Function CHRFAM7A alleles studied vitro two disease relevant phenotypic readouts: electrophysiology Aβ uptake. Genome edited induced pluripotent stem cells (iPSC) were used as model system with context. Double blind...
The differentiation of uterine stromal fibroblasts into decidual cells is critical for establishing pregnancy. This process, called decidualization, requires the reorganization actin cytoskeleton, which mainly depends on dynamics and phosphorylation status myosin light chain. We manipulated with jasplakinolide (100 nM) latrunculin B (1 microM), both significantly inhibited synthesis decidualization markers induced by 6 days treatment embryo-mimicking stimulus interleukin 1beta (IL1B) steroid...
Abstract The α7 nicotinic acetylcholine receptor (α7nAChR) has been a promising target for diseases affecting cognition and higher cortical functions; however, the effect observed in animal models failed to translate into human clinical trials identifying translational gap. CHRFAM7A is human-specific fusion gene with properties that enable incorporation α7nAChR and, being specific, was not accounted preclinical studies. We hypothesized may account this gap understanding its function offer...
Neuroinflammation in Alzheimer's disease (AD) has been the focus for identifying targetable pathways drug development. The role of amyloid beta (Aβ), a prototype damage-associated molecular patterns (DAMPs), implicated triggering an inflammatory response. As alpha7 nicotinic acetylcholine receptor (α7 nAChR) binds Aβ with high affinity, α7 nAChR may play Aβ-induced neuroinflammation. conundrum how as mediator cholinergic anti-inflammatory response trigger not resolved. CHRFAM7A, uniquely...
Differentiation of stromal cells into decidual cells, which is critical to successful pregnancy, represents a complex transformation requiring changes in cytoskeletal architecture. We demonstrate that vitro differentiation human uterine fibroblasts includes down-regulation alpha-smooth muscle actin and beta-tubulin, phosphorylation focal adhesion kinase, redistribution vinculin. This accompanied by varied fibronectin modified ability migrate. Cytoskeletal organization determined primarily...
While advancements in imaging techniques have led to major strides deciphering the human brain, successful interventions are elusive and represent some of most persistent translational gaps medicine. Human restricted CHRFAM7A has been associated with neuropsychiatric disorders.
Myosin IC is a single headed member of the myosin superfamily that localizes to cytoplasm and nucleus implicated in variety processes both compartments. We recently identified novel isoform showed MYOIC gene mammalian cells encodes three isoforms (isoforms A, B, C) differ only addition short isoform-specific N-terminal peptides. The expression pattern mechanisms regulation remain unknown. To determine patterns isoforms, we performed comprehensive analysis two (isoform A B) contain sequences....
Transcriptional coactivator with PDZ-binding motif (TAZ) is known to bind a variety of transcription factors control cell differentiation and organ development. However, its role in uterine physiology has not yet been described. To study regulation during the unique process fibroblasts into decidual cells (decidualization), we utilized human fibroblast (HuF) vitro model. Immunocytochemistry data demonstrated that majority TAZ protein localized nucleus. Treatment HuF embryonic stimulus...
Myosin IC is a single headed member of the myosin superfamily. We recently identified novel isoform and showed that MYOIC gene in mammalian cells encodes three isoforms (isoforms A, B, C). Furthermore, we demonstrated A but not B exhibits tissue specific expression pattern. In this study, extended our analysis patterns by analyzing protein mRNA various cell lines prostate specimens tumor tissues from transgenic mouse (TRAMP) model immunoblotting, qRT-PCR, indirect immunohistochemical...
Distribution of the α subunit stimulatory G protein (G s α) was analyzed in membrane and cytosolic (supernatant 200 000 g ) fractions from rat cortex, thalamus hippocampus during course post‐natal development. In parallel, changes β‐adrenoceptor density adenylyl cyclase activity were determined. Long αL) short αS) variants assessed by immunoblotting using specific polyclonal antisera reacting with both isoforms. Post‐natal development associated an increase total amount brain α. αL dominant...
In vitro differentiation of human pluripotent stem cell into relevant types is a desirable model system that has the biological context, renewable source, and scalable. GABA interneurons basal forebrain cholinergic neurons, derivates medial ganglionic eminence (MGE), are implicated in diverse neuropsychiatric diseases. Various protocols have been proposed to generate MGE progenitors: embryoid body- (EB-) based rosette-derived (RD), adherent (AdD), nonadherent (NAdD) approaches. While Wnt...
Abstract Background CHRFAM7A is a human‐restricted gene associated with neuropsychiatric and neurodegenerative disorders. The translated protein incorporates into the α7 nicotinic acetylcholine receptor (α7nAChR) leading to hypomorphic receptor. Mechanistic insight from isogenic iPSC derived neuronal mononuclear cells demonstrated that affects Ca 2+ signaling activates small GTPase Rac1 an actin cytoskeleton gain of function. Fundamental differences in tissue stiffness human rodent brain are...
Abstract Background Understanding the fundamental differences between human and pre‐human brain is a prerequisite for designing meaningful models therapies AD. Expressed CHRFAM7A , restricted gene with carrier frequency of 75% in population predicts profound translational significance. Method The physiological role explored using multiomics approach on 600 post mortem tissue samples (ROSMAP). emerging pathways are tested validated an isogenic hiPSC model knock‐in neurons monocytes. In vivo...