A5040168097- Sphingolipid Metabolism and Signaling
- Genomics and Chromatin Dynamics
- DNA and Nucleic Acid Chemistry
- Ion Transport and Channel Regulation
- Hippo pathway signaling and YAP/TAZ
- Cellular Mechanics and Interactions
- Cell Adhesion Molecules Research
- Clusterin in disease pathology
- Neonatal Respiratory Health Research
- Angiogenesis and VEGF in Cancer
- Nuclear Structure and Function
- Phagocytosis and Immune Regulation
- Heat shock proteins research
- Cancer therapeutics and mechanisms
- Inflammasome and immune disorders
- Axon Guidance and Neuronal Signaling
- Hydrogen's biological and therapeutic effects
- NF-κB Signaling Pathways
- Caveolin-1 and cellular processes
- Tracheal and airway disorders
- ATP Synthase and ATPases Research
- interferon and immune responses
- Protein Kinase Regulation and GTPase Signaling
- Immune Cell Function and Interaction
- MicroRNA in disease regulation
Illinois College
2019-2024
University of Illinois Chicago
2017-2024
Center for Vascular Biology Research
2023-2024
University of Illinois Urbana-Champaign
2019-2021
National Institute of Immunology
2018
All India Institute of Medical Sciences
2011-2016
The vascular endothelial growth factor-A (VEGF-A)-VEGFR2 pathway drives tumor vascularization by activating proangiogenic signaling in cells (ECs). Here, we show that EC-sphingosine-1-phosphate receptor 1 (S1PR1) amplifies VEGFR2-mediated angiogenic to enhance growth. We cancer induce S1PR1 activity ECs, and thereby, conditional deletion of ECs (EC-S1pr1−/− mice) impairs Mechanistically, engages the heterotrimeric G-protein Gi, which VEGF-VEGFR2 due an increase tyrosine kinase c-Abl1....
Acute lung injury (ALI) is a lethal inflammatory disorder whose incidence on the rise. Alveolar macrophages normally act to resolve inflammation, but when dysregulated they can provoke ALI. We demonstrate that monocyte-derived (CD11b+ macrophages) recruited into airspace upregulate anti-inflammatory function of alveolar by suppressing their stimulator type 1 interferon gene (STING) signaling. Depletion CD11b+ in mice (macrophagedep mice) after endotoxin or Pseudomonas aeruginosa causes...
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Regenerating vascular endothelium under sepsis, trauma, and viral infections is vital for promoting the resolution of inflammatory diseases such as acute lung injury (ALI). Transient receptor potential canonical (TRPC) channels mediated Ca2+ entry compromises organ functions survival from injury. Through decoding domain in TRPC6 responsible injury, we unveiled intricate molecular mechanisms underlying regeneration injured tissue. We found that substitution isoleucine111 within Ist ankyrin...
The mechanical environment generated through the adhesive interaction of endothelial cells (ECs) with matrix controls nuclear tension, preventing aberrant gene synthesis and transition from restrictive to leaky endothelium, a hallmark acute lung injury (ALI). However, mechanisms controlling tension transmission nucleus EC-restrictive fate remain elusive. Here, we demonstrate that, in kinase-independent manner, focal adhesion kinase (FAK) safeguards maintain fate. In FAK-depleted ECs, robust...
Increased lung vascular permeability and neutrophilic inflammation are hallmarks of acute injury. Alveolar macrophages (AMϕ), the predominant sentinel cell type in airspace, die massive numbers while fending off pathogens. Recent studies indicate that AMϕ pool is replenished by airspace-recruited monocytes, but mechanisms instructing conversion recruited monocytes into reparative remain elusive. Cyclic AMP (cAMP) a barrier protective immunosuppressive second messenger lung. Here, we...
The high mobility group A1 (HMGA1) are non-histone chromosomal proteins consisting of HMGA1a and HMGA1b which act as architectural transcription factors. Elevated levels HMGA1 reported in a number human cancers suggested tumor markers. Due to their role neoplastic transformation progression, we considered potential target for downregulation at the transcriptional level. present paper deals with binding widely used chemotherapeutic agent, adriamycin (ADM), hmga1gene promoter (−304 −284),...
High-mobility group A1 (HMGA1) is a non-histone chromosomal protein, which known as ‘architectural’ transcription factor that facilitates the assembly of ‘enhanceosome.’ Because its elevated expression in number human malignancies, with barely minimal levels healthy adults, HMGA1 considered potential ‘tumor marker.’ Therefore, we looked at inhibition hmga1 using anti-gene strategy, an attractive therapeutic approach. This was achieved by two triplex forming oligonucleotides (TFOs), TFO1 and...
We have recently uncovered that endothelial cell (EC) S1PR1 controls the effectiveness of VEGFR2 driven tumor angiogenesis. By using ECs, EC-S1PR1−/- mice and antagonist, we showed VEGF-VEGFR2 pathway requires EC-S1PR1-induced signaling to efficiently drive vascularization growth, indicating combining antagonist with anti-VEGF/VEGFR2 therapy may eradicate resistant tumors.
High mobility group A1 (HMGA1), a non-histone chromosomal protein, is highly expressed in wide range of human cancers including cervical, breast, and prostate cancers. Therefore, hmga1 gene considered as an attractive potential target for anticancer drugs. We have chosen 27 bp DNA sequence from regulatory region promoter studied its interaction with adriamycin (ADM) vitro expression HMGA1 the presence ADM HeLa cell line. A variety biophysical techniques were employed to understand...
Neutrophils (PMNs) reside as a marginated pool within the vasculature, ready for deployment during infection. However, how endothelial cells (ECs) control PMN extravasation and activation to strengthen tissue homeostasis remains ill-defined. Here, we found that vascular ETS-related gene (ERG) is generalized mechanism regulating activity in preclinical injury models human patients. We show ERG loss ECs rewired PMN-transcriptome, enriched genes associated with CXCR2-CXCR4 signaling. Rewired...
Vascular endothelium, the inner most lining of all blood vessels, controls transport nutrients, protein, water, and leukocytes across vessel wall thereby maintains lung tissue fluid homeostasis. Damage to endothelial integrity caused by mediagenic, inflammatory, or toxic agents results in pulmonary edema, inflammation, organ failure, high lethality. A key pathogenic characteristic vascular injury involves an excessive loss cells (EC) accompanied generation inflammatory cytokines. Genome-wide...
Impairment of endothelial barrier integrity causes vascular injury leading to acute lung (ALI), which, if not resolved, can compromise a patient’s functions and mortality. While it is known that both cells (EC) their underlying extracellular matrix (ECM) are required for preserving homeostasis functions, much the efforts understand mechanisms regulating these have focused mainly on EC. A fundamental unresolved question whether lung-remodeled ECM formed due leaky endothelium impacts EC so,...
In the lungs, phenotypically different alveolar macrophages (AMs) co-exist with interstitial monocyte-derived (Mo-Macs) to regulate lung homeostasis. We have shown that airspace-recruited Mo-Macs resolve inflammation, restoring lung-fluid Analyzing publicly available datasets (Immgen Consortium), we found compared Mo-Macs, AMs are also enriched pathways regulating mitochondria function, but their significance remain elusive. During development, generated by differentiation of lung-recruited...
Sphingosine‐1‐phosphate (S1P) activation of sphingosine‐1‐phosphate receptor 1 (S1PR1) in endothelial cells (ECs) strengthens the barrier and prevents lung injury. However mechanisms regulating EC‐S1PR1 expression remains unclear. Recently, we showed that endothelial‐specific deletion focal adhesion kinase (FAK) mice severely disrupted vascular function. Microarray analysis FAK depleted a marked reduction S1PR1 expression. Thus, tested hypothesis impaired synthesis is responsible for...
Abstract Vascular endothelium forms a restrictive barrier to defend the underlying tissue against uncontrolled influx of circulating protein and immune cells. Mechanisms that mediate transition from leaky endothelium, hallmark injury exemplified by acute lung (ALI), remain elusive. Using endothelial cell (EC)-Fak -/- mice, we show FAK sensing transmission mechanical tension EC nucleus governs fate. In FAK- deleted EC, increased induced Rho kinase caused tyrosine phosphorylation nuclear...
Sphingosine‐1‐phosphate receptor 1 (S1PR1) signaling has been implicated in regulation of vascular permeability, lymphocyte trafficking, inflammation, and cardiac function. In endothelial cells (ECs), S1PR1 stimulates Gi‐dependent intracellular cascades, which enhances barrier ECs regulate primary host defense mechanism. this study, we used S1PR1‐GFP reporter mice to determine dynamics activity the lung response endotoximia during injury resolution. These mice, having S1pr1 knockin vector...
Lung macrophages (M Φ ) are important in triggering the immune response and thereby resolve acute lung injury (ALI) by sensing pathogens through pattern recognizing receptors including TLRs. However, role of resolving inflammation is less well understood. Herein, we used transgenic mice expressing human diphtheria toxin receptor (DTR) under control Cd11b‐promoter to assess their specific regulating inflammatory injury. Administration (DT) DTR selectively depletes CD11b cells causing...
Loss of endothelial barrier function is a hall mark acute lung injury, which induces 40% lethality in affected patients. Sphingosine‐1‐phosphate receptor 1 (S1PR1) upon ligating S1P on cell (EC) surface enhances and reverses vascular hyper‐permeability variety inflammatory injury including endotoxin, LPS. Whether S1PR1 activated dynamically following ECs repairs exclusively through EC‐cell signaling remains enigmatic. Using S1PR1‐GFP‐signaling reporter mice (S1PR1 reporter) mice, nuclear GFP...