A5090167798- Eosinophilic Esophagitis
- Protease and Inhibitor Mechanisms
- Ovarian cancer diagnosis and treatment
- Cancer-related molecular mechanisms research
- Connective tissue disorders research
- Peptidase Inhibition and Analysis
- Plant Molecular Biology Research
- Helicobacter pylori-related gastroenterology studies
- Bone and Dental Protein Studies
- Colorectal Cancer Treatments and Studies
- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Light effects on plants
- Inflammatory Bowel Disease
- Microscopic Colitis
- Dermatological and Skeletal Disorders
- Circadian rhythm and melatonin
- Bone Metabolism and Diseases
- Lipid metabolism and disorders
- Growth Hormone and Insulin-like Growth Factors
- Ferroptosis and cancer prognosis
- Blood Coagulation and Thrombosis Mechanisms
- Cancer, Stress, Anesthesia, and Immune Response
- RNA and protein synthesis mechanisms
- Digestive system and related health
Virginia Tech
2020-2021
Icahn School of Medicine at Mount Sinai
2008-2014
Genomics (United Kingdom)
2014
Mount Sinai Hospital
2011
Pediatrics and Genetics
2007
The 'vanishing bone' or inherited osteolysis/arthritis syndromes represent a heterogeneous group of skeletal disorders characterized by mineralization defects affected bones and joints. Differing in anatomical distribution, severity associated syndromic features, gene identification each disorder should provide unique insights into genetic/molecular pathways contributing to the overall control growth development. We previously described then demonstrated that novel autosomal recessive...
Peutz–Jeghers syndrome (PJS) is a rare hereditary disorder resulting from mutations in serine/threonine kinase 11 (STK11) and characterized by gastrointestinal (GI) hamartomatous polyps, mucocutaneous pigmentation, an increased risk for specific cancers. Little known about the genetic implications of STK11 with regard to their role dysplastic malignant transformation GI polyps. Peripheral blood genomic DNA samples 116 Chinese PJS patients 52 unrelated families were investigated mutations....
Abstract Background We sought to identify candidate serum biomarkers for the detection and surveillance of EOC. Based on RNA-Seq transcriptome analysis patient-derived tumors, highly expressed secreted proteins were identified using a bioinformatic approach. Methods was used quantify papillary serous ovarian cancer transcriptomes. Paired end sequencing 22 flash frozen tumors performed. Sequence alignments processed with program ELAND, expression levels ERANGE then bioinformatically screened...
RNA-Seq allows a theoretically unbiased analysis of both genome-wide transcription levels and mutation status tumor. Using this technique we sought to identify novel candidate therapeutic targets expressed in epithelial ovarian cancer (EOC).Specifically, invasion/migration based on expression across all tumors, novelty EOC, known function. revealed the high CD151, transmembrane protein, stages EOC. Expression was confirmed at mRNA protein using RT-PCR immunohistochemical staining,...
In mammals, a set of core clock genes form transcription-translation feedback loops to generate circadian oscillations. We and others recently identified novel transcript at the Period2 (Per2) locus that is transcribed from antisense strand Per2 This transcript, Per2AS, expressed rhythmically antiphasic mRNA, leading our hypothesis Per2AS mutually inhibit each other's expression double negative loop. By perturbing we found transcription, but not represses However, does repress as knockdown...
Multicentric osteolysis with arthropathy (MOA; MIM 605156) is an inherited osteolyses and arthritis syndrome resulting from loss of matrix metalloproteinase 2 (MMP-2). We recently demonstrated that Mmp2(-/-) mice represent a unique model for the study human disease, sharing many features including skeletal dysplasia defects in osteoblast behavior. therefore sought to explore secondary molecular effects MMP-2 loss, which coexist underlying phenotypes. used quantitative real-time RT-PCR...
Abstract Background and Aims NX-13 activation of NLRX1 reduces intracellular reactive oxygen species decreases inflammation in animal models colitis. A phase 1a trial demonstrated a gut-selective pharmacokinetic profile with good tolerability. This Ib study aimed to evaluate the safety, tolerability, pharmacokinetics patients active ulcerative colitis [UC]. Methods We conducted multicentre, randomized, double-blind, placebo-controlled UC. Patients Mayo Clinic Score 4–10 were randomly...
Abstract Background Immunometabolism exerts a bimodal action at the interface of extracellular immune response and intracellular metabolism. It controls both processes inflammatory responses by regulating cellular energy supply & demands, factors that determine how cell responds to signals. Hence, immunometabolic pathways represent an attractive target as gate entry checkpoint for cascade. Nucleotide-binding oligomerization domain, Leucine Rich repeat containing X1 (NLRX1) PLeXin...
Abstract: Inactivating mutations of matrix metalloproteinase 2 ( MMP2 ) cause multicentric osteolysis with nodulosis and arthritis, one a group inherited osteolytic arthritic disorders. We have previously shown that mice lacking Mmp2 share similar syndromic features the human disorder, at cellular level, -/- mouse osteoblasts osteoclasts reduced numbers proliferation rates critical developmental time points. While hypothesized, effect loss on apoptosis has not been examined in this system....
Elementary cellular biology teaches that proteins are the main actors within cells. In addition, DNA carries genetic information and mRNA serves as go-between molecule to create protein using code from DNA. Recent advances in sequencing technologies have revealed a large portion of our is transcribed even though it does not appear encode proteins. Further studies shown many these non-coding RNAs (ncRNAs) serve regulatory functions Here, we examine role such molecules regulation circadian...
Abstract Background Although the precise role of eosinophils in IBD is debated, elevated may influence response to therapy and clinical outcomes1. Thus, therapeutic agents which affect both neutrophil eosinophil recruitment provide more robust improvement patients with UC. NLRX1 an immunometabolic protein reduces oxidative stress, shifts cellular metabolism, decreases inflammation multiple cell types implicated ulcerative colitis (UC). Studies agonists (gut-selective NX-13 & systemic...
Abstract Background NLRX1 activation reduces inflammation by decreasing oxidative stress and altering cellular metabolism within multiple cell types implicated in ulcerative colitis (UC). Colitis animal models demonstrated reduced disease severity a phase 1b clinical trial showed signs of rapid symptom endoscopic improvement patients with active UC.1, 2 Abdominal pain driven visceral hypersensitivity may persist even after has resolved, negatively affecting their quality life.3, 4...
Abstract Background In mouse models, NX-13 is an orally active, gut-restricted NLRX1 agonist that has been shown to reduce severity of disease in multiple UC models through a novel immunometabolic, bimodal mechanism. Most preclinical studies rely upon rodent the human gastrointestinal physiology, microbiome, and immune system bear greater similarity pigs. Therefore, we sought expand validate our results mice using dextran sulfate sodium (DSS) pig model colitis. Here, describe severity,...
Abstract Background PLXDC2 is expressed on the cell surface of macrophage, dendritic and specific mesenchymal epithelial cells whose activation shifts cellular metabolism reduces oxidative stress to rebalance immune response decrease inflammation. It’s role in IBD pathogenesis unknown. improves disease severity rheumatoid arthritis models1, while loss exacerbates DSS colitis2. PX-04 a novel, first-in-class, orally active agonist. Here, we report consequences activating using an acute colitis...
Abstract Background In rodent models of ulcerative colitis (UC), NX-13 (as an orally active, gut selective NLRX1 agonist) improves disease activity through a novel bimodal mechanism. Subsequently, pig DSS experiment was performed to generate pharmacokinetic (PK) and mechanistic insights, given pigs can be dosed with tablets their gastrointestinal physiology, microbiome, immune system is markedly more similar humans than rodents are. We here describe the efficacy PK in compared phase 1...