A5019274721- Pregnancy and preeclampsia studies
- Birth, Development, and Health
- Reproductive System and Pregnancy
- MicroRNA in disease regulation
- Receptor Mechanisms and Signaling
- Autophagy in Disease and Therapy
- Estrogen and related hormone effects
- Neuroscience of respiration and sleep
- Prenatal Screening and Diagnostics
- Extracellular vesicles in disease
- Adipose Tissue and Metabolism
- Neonatal Health and Biochemistry
- Biochemical effects in animals
- Gestational Diabetes Research and Management
- Neuropeptides and Animal Physiology
- Erythrocyte Function and Pathophysiology
- Immune Cell Function and Interaction
- Pregnancy and Medication Impact
- Heme Oxygenase-1 and Carbon Monoxide
- Epigenetics and DNA Methylation
- Bipolar Disorder and Treatment
- Gout, Hyperuricemia, Uric Acid
- Endoplasmic Reticulum Stress and Disease
- Blood Coagulation and Thrombosis Mechanisms
- Circadian rhythm and melatonin
Women & Infants Hospital of Rhode Island
2015-2024
Brown University
2015-2024
Providence College
2019-2020
University of Toyama
2018
Shanghai East Hospital
2017
Rhode Island Hospital
2011-2013
Louisiana State University Health Sciences Center New Orleans
2009
Kagoshima University
1999-2003
Hyogo Medical University
1999
Systemic manifestation of preeclampsia (PE) is associated with circulating factors, including inflammatory cytokines and damage-associated molecular patterns (DAMPs), or alarmins. However, it unclear whether the placenta directly contributes to increased levels these triggers. Here, we demonstrate that pyroptosis, a unique cell death pathway, occurs in predominantly from early onset PE, as evidenced by elevated active caspase-1 its substrate cleaved products, gasdermin D (GSDMD), IL-1β,...
GPER is a G(s)-coupled seven-transmembrane receptor that has been linked to specific estrogen binding and signaling activities are manifested by plasma membrane-associated enzymes. However, in many cell types, predominately localized the endoplasmic reticulum (ER), only minor amounts of detectable at surface, an observation caused controversy regarding its role as membrane receptor. Here, we show constitutively buds intracellularly into EEA-1+ endosomes from clathrin-coated pits. Nonvisual...
Hyperuricemia is an independent risk factor for CKD and contributes to kidney fibrosis. In this study, we investigated the effect of EGF receptor (EGFR) inhibition on development hyperuricemic nephropathy (HN) mechanisms involved. a rat model HN induced by feeding mixture adenine potassium oxonate, increased EGFR phosphorylation severe glomerular sclerosis renal interstitial fibrosis were evident, accompanied dysfunction urine microalbumin excretion. Administration gefitinib, highly...
The etiology of preeclampsia (PE), a serious pregnancy complication, remains an enigma. We have demonstrated that proteinopathy, pathologic feature neurodegenerative diseases, is key observation in the placenta and serum from PE patients. hypothesize macroautophagy/autophagy machinery mediates degradation aggregated proteins damaged organelles impaired PE. Here, we show TFEB (transcription factor EB), master transcriptional regulator lysosomal biogenesis, its regulated proteins, LAMP1,...
Pregnancy is a stress factor culminating into mild endoplasmic reticulum (ER) stress, which necessary for placental development. However, excessive or chronic ER in pre-eclamptic placentas leads to dysfunction. The precise mechanisms through impacts trophoblasts are not well understood. Here, we showed that reduces the number of lysosomes, resulting inhibition autophagic flux trophoblast cells. also disrupted translocation lysosomes surface cells, and inhibited lysosomal exocytosis, whereby...
Preeclampsia is a major pregnancy complication with potential short- and long-term consequences for both mother fetus. Understanding its pathogenesis causative biomarkers likely to yield insights prediction treatment. Herein, we provide evidence that transthyretin, transporter of thyroxine retinol, aggregated in preeclampsia present at reduced levels sera preeclamptic women, as detected by proteomic screen. We demonstrate transthyretin aggregates form deposits placental tissue cause...
Herpes simplex type 1 (HSV1) replicates in epithelial cells and secondarily enters local sensory neuronal processes, traveling retrograde to the nucleus enter latency. Upon reawakening newly synthesized viral particles travel anterograde back of lip, causing recurrent cold sore. HSV1 co-purifies with amyloid precursor protein (APP), a cellular transmembrane glycoprotein receptor for transport machinery that when proteolyzed produces A-beta, major component senile plaques. Here we focus on...
Abstract In preeclampsia, the serum levels of transthyretin, a carrier protein for thyroxine, are elevated. Transthyretin isolated from preeclamptic is also aggregated and can induce preeclampsia-like symptoms in pregnant IL10 −/− mice. Using western blotting, immunofluorescence, ELISA qRT-PCR, we investigated production transthyretin by placentae whether carried into maternal circulation via placental extracellular vesicles. Both total were present higher compared to normotensive (p <...
Lactic acid (LA) metabolism in the tumor microenvironment contributes to establishment and maintenance of immune tolerance. This pathway is characterized associated macrophages. However, role LA at maternal-fetal interface during early pregnancy, especially decidual macrophage differentiation, are still unclear. Herein, for first time, we discovered that can trigger either M2 or M1 polarization via oxidative phosphorylation glycolysis regulation under normoxia hypoxia, respectively. Also,...
Abstract A non-invasive and sensitive blood test has long been a goal for early stage disease diagnosis treatment Alzheimer’s (AD) other proteinopathy diseases. We previously reported that preeclampsia (PE), severe pregnancy complication, is another disorder with impaired autophagy. hypothesized induced autophagy deficiency would promote accumulation of pathologic protein aggregates. Here, we describe novel, assay detects serum aggregates from patients PE (n = 33 onset late onset)...
Abstract The etiology of preeclampsia (PE), a severe complication pregnancy with several clinical manifestations and high incidence maternal fetal morbidity mortality, remains unclear. This issue is major hurdle for effective treatment strategies. We recently demonstrated that PE exhibits an Alzheimer-like impaired autophagy proteinopathy in the placenta. Targeting these pathological pathways may be novel therapeutic strategy PE. Stimulation natural disaccharide trehalose its lacto analog...
Abstract DC-NK cell interactions are thought to influence the development of maternal tolerance and de novo angiogenesis during early gestation. However, it is unclear which mechanism ensures cooperative dialogue between DC NK cells at feto-maternal interface. In this article, we show that uterine key source IL-10 required regulate phenotype pregnancy success. Upon in vivo expansion gestation, expressed increased levels IL-10. Exogenous administration was sufficient overcome failure dams...
We have previously described that placental activation of autophagy is a central feature normal pregnancy, whereas impaired in preeclampsia (PE). Here, we show hypoxia–reoxygenation (H/R) treatment dysregulates key molecules maintain autophagy–lysosomal flux primary human trophoblasts (PHTs). Ultrastructural analysis using transmission electron microscopy reveals significant reduction autophagosomes and autolysosomes H/R-exposed PHTs. H/R-induced accumulation protein aggregates follows...
The structural determinants of nicotinic acetylcholine receptor (AChR) trafficking have yet to be fully elucidated. Hydrophobic residues occur within short motifs important for endoplasmic reticulum (ER) export or endocytotic trafficking. Hence, we tested whether highly conserved hydrophobic residues, primarily leucines, in the cytoplasmic domain α4β2 AChR subunits were required cell surface expression AChRs. Mutation F350, L351, L357, and L358 alanine α4 subunit attenuates mutant F342,...