A5012931368- Cassava research and cyanide
- Metabolomics and Mass Spectrometry Studies
- Angiogenesis and VEGF in Cancer
- Nitric Oxide and Endothelin Effects
- Regulation of Appetite and Obesity
- Zebrafish Biomedical Research Applications
- Liver Disease Diagnosis and Treatment
- Cell Adhesion Molecules Research
- Congenital heart defects research
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Pharmacology and Obesity Treatment
- Diet and metabolism studies
- Pregnancy and preeclampsia studies
- Pancreatic function and diabetes
- COVID-19 Clinical Research Studies
- Pesticide Exposure and Toxicity
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Cardiovascular Conditions and Treatments
- Diabetes Treatment and Management
- Wound Healing and Treatments
- Biochemical Analysis and Sensing Techniques
- Mitochondrial Function and Pathology
- Drug-Induced Hepatotoxicity and Protection
Beth Israel Deaconess Medical Center
2018-2024
Harvard University
2013-2024
Broad Institute
2013-2023
Massachusetts General Hospital
2013-2023
Cardiovascular Institute Hospital
2021
Hadassah Medical Center
2020
Center for Systems Biology
2017
Yale University
2000-2011
University of California, Los Angeles
2006
Cedars-Sinai Medical Center
2005
Leptin is a hormone that regulates food intake, and its receptor (OB-Rb) expressed primarily in the hypothalamus. Here, it shown OB-Rb also human vasculature primary cultures of endothelial cells. In vitro vivo assays revealed leptin has angiogenic activity. vivo, induced neovascularization corneas from normal rats but not fa/fa Zucker rats, which lack functional receptors. These observations indicate vascular endothelium target for suggest physiological mechanism whereby leptin-induced...
The role of the cardiac myocyte as a mediator paracrine signaling in heart has remained unclear. To address this issue, we generated mice with myocyte-specific deletion vascular endothelial growth factor gene, thereby producing cardiomyocyte-specific knockout secreted factor. hearts these had fewer coronary microvessels, thinned ventricular walls, depressed basal contractile function, induction hypoxia-responsive genes involved energy metabolism, and an abnormal response to β-adrenergic...
We have identified conditions for forming cultured human umbilical vein endothelial cells (HUVEC) into tubes within a three-dimensional gel that on implantation immunoincompetent mice undergo remodeling complex microvessels lined by endothelium. HUVEC suspended in mixed collagen/fibronectin gels organize cords with early lumena 24 h and then apoptose. Twenty-hour constructs, s.c. implanted immunodeficient mice, display HUVEC-lined thin-walled the 31 days after implantation....
In addition to having a major role in energy homeostasis, leptin is emerging as pleiotropic cytokine with multiple physiological effector functions. The recently discovered proangiogenic activity of suggested the hypothesis that its production might be regulated by hypoxia, are other angiogenic factors. To examine this proposal, expression protein and mRNA was measured found markedly up-regulated response ambient or chemical hypoxia (upon exposure desferrioxamine cobalt chloride), an effect...
Leptin, a 16 kDa pleiotropic cytokine primarily expressed in adipose tissue, has been shown to cause multiple systemic biological actions. Recently, leptin also documented as an important component of the wound healing process and its receptor appears be tissue. We have previously demonstrated that is potent angiogenic factor exerting direct effects on endothelial cells transcription encoding gene regulated by hypoxia. Here, we hypothesize expression acutely up-regulated ischemic tissue...
Spectrin α2 (αII-spectrin) is a scaffolding protein encoded by the Spna2 gene and constitutively expressed in most tissues. Exon trapping of C57BL/6 mice allowed targeted disruption αII-spectrin. Heterozygous animals displayed no phenotype 2 years age. Homozygous deletion was embryonic lethal at day 12.5 to 16.5 with retarded intrauterine growth, craniofacial, neural tube cardiac anomalies. The loss αII-spectrin did not alter levels αI- or βI-spectrin, transcriptional any β-spectrin ankyrin,...
The discovery of metabolite-phenotype associations may highlight candidate biomarkers and metabolic pathways altered in disease states. We sought to identify novel metabolites associated with obesity one its major complications, nonalcoholic fatty liver (NAFLD), using a liquid chromatography-tandem mass spectrometry method. In 997 individuals Framingham Heart Study Generation 3 (FHS Gen 3), we identified an association between anandamide (AEA) BMI. Further examination revealed that AEA was...
Endothelial dysfunction accompanies the microvascular thrombosis commonly observed in severe COVID-19. Constitutively, endothelial surface is anticoagulant, a property maintained at least part via signaling through Tie2 receptor. During inflammation, antagonist angiopoietin-2 (Angpt-2) released from cells and inhibits Tie2, promoting prothrombotic phenotypic shift. We sought to assess whether COVID-19 associated with procoagulant alterations Tie2/angiopoietin axis. Primary HUVECs treated...
The STAT (signal transducer and activator of transcription) proteins play a crucial role in the regulation gene expression, but their targets manner which they select them remain largely unknown. Using chromatin immunoprecipitation DNA microarray analysis (ChIP-chip), we have identified regions human chromosome 22 bound by STAT1 STAT2 interferon-treated cells. Analysis genomic loci proximal to these binding sites introduced new candidate target genes, several are affiliated with...
Virtually all organisms seek to maximize fitness by matching fuel availability with energy expenditure. In vertebrates, glucose homeostasis is central this process, levels finely tuned match changing requirements. To discover new pathways regulating in vivo, we performed a large-scale chemical screen live zebrafish and identified the small molecule alexidine as potent glucose-lowering agent. We found that inhibits PTEN-like mitochondrial phosphatase PTPMT1 other pharmacological genetic means...
Recent advances in proteomic technologies have made high-throughput profiling of low-abundance proteins large epidemiological cohorts increasingly feasible. We investigated whether aptamer-based could identify biomarkers associated with future development type 2 diabetes (T2DM) beyond known risk factors. identified dozens markers highly significant associations T2DM across longitudinal (n = 2839) followed for up to 16 years. leveraged proteomic, metabolomic, genetic, and clinical data from...
Age-related deficits in skeletal muscle function, termed sarcopenia, are due to loss of mass and changes the intrinsic mechanisms underlying contraction. Sarcopenia is associated with falls, functional decline, mortality. Electrical impedance myography (EIM)-a minimally invasive, rapid electrophysiological tool-can be applied animals humans monitor health, thereby serving as a biomarker both preclinical clinical studies. EIM has been successfully employed several species; however,...
Angiogenesis is regulated by means of a balance between activators and inhibitors. However, little known regarding the regulation quiescent state adult vessels. Corticotropin-releasing factor receptor 2 (CRFR2) found in both endothelial smooth muscle cells (SMCs) vasculature, where its function has remained elusive. We have investigated role CRFR2 as determinant tissue vascularization comparing control CRFR2-deficient mice with immunohistological morphometric techniques. To define mechanisms...
Exposure to cyanide causes a spectrum of cardiac, neurological, and metabolic dysfunctions that can be fatal. Improved antidotes are needed, but the ideal biological pathways target not known. To understand better effects discover novel antidotes, we developed zebrafish model exposure scaled it for high-throughput chemical screening. In screen 3120 small molecules, discovered 4 block toxicity. The most potent antidote was riboflavin. Metabolomic profiling cyanide-treated revealed changes in...
Throughout a vertebrate organism’s lifespan, skeletal muscle mass and function progressively decline. This age-related condition is termed sarcopenia. In humans, sarcopenia associated with risk of falling, cardiovascular disease, all-cause mortality. As the world population ages, projected to reach 2 billion older adults worldwide in 2050, economic burden on healthcare system also increase considerably. Currently, there are no pharmacological treatments for sarcopenia, given long-term nature...
Nitric oxide (NO) has been demonstrated to mediate events during ovulation, pregnancy, blastocyst invasion and preimplantation embryogenesis. However, less is known about the role of NO postimplantation development. Therefore, in this study, we explored effects vascular development murine yolk sac, which begins shortly after implantation. Establishment vitelline circulation crucial for normal embryonic growth Moreover, functional inactivation endodermal layer sac by environmental insults or...
Background Cardiovascular development is vital for embryonic survival and growth. Early gestation embryo loss or malformation has been linked to yolk sac vasculopathy congenital heart defects (CHDs). However, the molecular pathways that underlie these structural in humans remain largely unknown hindering of molecular-based diagnostic tools novel therapies. Methodology/Principal Findings Murine embryos were exposed high glucose, a condition known induce cardiovascular both animal models...
Abstract G protein‐coupled receptors (GPCRs) comprise the largest group of membrane in eukaryotic genomes and collectively they regulate nearly all cellular processes. Despite widely recognized importance this class proteins, many GPCRs remain understudied. receptor 27 (Gpr27) is an orphan GPCR that displays high conservation during vertebrate evolution. Although, GPR27 known to be expressed tissues metabolism including pancreas, skeletal muscle, adipose tissue, its functions are poorly...
Objective As there is significant heterogeneity in the weight loss response to pharmacotherapy, one of most important clinical questions obesity medicine how predict an individual’s pharmacotherapy. The present study examines patterns among overweight and obese women who demonstrated early robust twice daily exenatide treatment compared those treated with hypocaloric diet matched placebo injections. Methods We randomized 182 (BMI 25-48 kg/m2) alone or injections plus diet. In both groups, ≥...
Little is understood about the embryonic development of sociality. We screened 1120 known drugs and found that inhibition topoisomerase IIα (Top2a) resulted in lasting social deficits zebrafish. In mice, prenatal Top2 caused defects interaction communication, which are behaviors relate to core symptoms autism. Mutation Top2a zebrafish down-regulation a set genes highly enriched for associated with autism humans. Both Top2a-regulated autism-associated gene sets have binding sites polycomb...