Publications by authors named "Vijay Avin Balaji Ragunathrao"

4 Publications

  • Page 1 of 1

Using machine learning to develop a novel COVID-19 Vulnerability Index (C19VI).

Sci Total Environ 2021 Jun 5;773:145650. Epub 2021 Feb 5.

Department of Microbiology and Immunology, UIC, Chicago, IL, USA.

COVID-19 is now one of the most leading causes of death in the United States (US). Systemic health, social and economic disparities have put the minorities and economically poor communities at a higher risk than others. There is an immediate requirement to develop a reliable measure of county-level vulnerabilities that can capture the heterogeneity of vulnerable communities. This study reports a COVID-19 Vulnerability Index (C19VI) for identifying and mapping vulnerable counties. We proposed a Random Forest machine learning-based vulnerability model using CDC's sociodemographic and COVID-19-specific themes. An innovative 'COVID-19 Impact Assessment' algorithm was also developed for evaluating severity of the pandemic and to train the vulnerability model. Developed C19VI was statistically validated and compared with the CDC COVID-19 Community Vulnerability Index (CCVI). Finally, using C19VI and the census data, we explored racial inequalities and economic disparities in COVID-19 health outcomes. Our index indicates that 575 counties (45 million people) fall into the 'very high' vulnerability class, 765 counties (66 million people) in the 'high' vulnerability class, and 1435 counties (204 million people) in the 'moderate' or 'low' vulnerability class. Only 367 counties (20 million people) were found as 'very low' vulnerable areas. Furthermore, C19VI reveals that 524 counties with a racial minority population higher than 13% and 420 counties with poverty higher than 20% are in the 'very high' or 'high' vulnerability classes. The C19VI aims at helping public health officials and disaster management agencies to develop effective mitigation strategies especially for the disproportionately impacted communities.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862885PMC
June 2021

Programming to S1PR1 Endothelial Cells Promote Restoration of Vascular Integrity.

Circ Res 2021 Apr 30. Epub 2021 Apr 30.

Pharmacology and Regerative Medicine, University of Illinois at Chicago College of Medicine, UNITED STATES.

Increased endothelial permeability and defective repair are the hallmarks of several vascular diseases including acute lung injury (ALI). However, little is known about the intrinsic pathways activating the endothelial cell (EC) regenerative programs. Studies have invoked a crucial role of sphingosine-1-phosphate (S1P) in resolving endothelial hyperpermeability through the activation of the G-protein coupled receptor, sphingosine-1-phosphate receptor 1 (S1PR1). Here we addressed mechanisms of generation of a population of S1PR1 EC and their pivotal role in restoring endothelial integrity. Studies were made using inducible EC-S1PR1 (iEC-S1PR1) mice and S1PR1-GFP reporter mice to trace the generation of S1PR1 EC. We observed in a mouse model of endotoxemia that S1P generation induced the programming of S1PR1 to S1PR1 EC, which eventually comprised 80% of the lung EC. The cell transition was required for reestablishing the endothelial junctional barrier. We observed that conditional deletion of S1PR1 in EC increased endothelial permeability. RNA-seq analysis of S1PR1 EC showed enrichment of genes regulating S1P synthesis and transport, specifically sphingosine kinase 1 (SPHK1) and SPNS2. Activation of transcription factors EGR1 and STAT3 was required for transcribing SPHK1 and SPNS2, respectively and both served to increase S1P production and amplify S1PR1 EC transition. Furthermore, transplantation of S1PR1 EC population into injured lung vasculature restored endothelial integrity. Our findings show that generation of the S1PR1 EC population activates the endothelial regenerative program to mediate endothelial repair. Results raise the possibility of harnessing this pathway to restore vascular homeostasis in inflammatory vascular injury states.
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http://dx.doi.org/10.1161/CIRCRESAHA.120.318412DOI Listing
April 2021

S1PR1 and VEGFR2 - a synergy that promotes tumor angiogenesis?

Mol Cell Oncol 2020 7;7(4):1746131. Epub 2020 Apr 7.

Department of Pharmacology and the Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL, USA.

We have recently uncovered that endothelial cell (EC) S1PR1 controls the effectiveness of VEGFR2 driven tumor angiogenesis. By using tumor ECs, EC-S1PR1 mice and S1PR1 antagonist, we showed that VEGF-VEGFR2 pathway requires EC-S1PR1-induced signaling to efficiently drive tumor vascularization and growth, indicating combining S1PR1 antagonist with anti-VEGF/VEGFR2 therapy may eradicate resistant tumors.
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http://dx.doi.org/10.1080/23723556.2020.1746131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469464PMC
April 2020

Sphingosine-1-Phosphate Receptor 1 Activity Promotes Tumor Growth by Amplifying VEGF-VEGFR2 Angiogenic Signaling.

Cell Rep 2019 12;29(11):3472-3487.e4

Department of Pharmacology and The Center for Lung and Vascular Biology, The University of Illinois College of Medicine, Chicago, IL 60612, USA. Electronic address:

The vascular endothelial growth factor-A (VEGF-A)-VEGFR2 pathway drives tumor vascularization by activating proangiogenic signaling in endothelial cells (ECs). Here, we show that EC-sphingosine-1-phosphate receptor 1 (S1PR1) amplifies VEGFR2-mediated angiogenic signaling to enhance tumor growth. We show that cancer cells induce S1PR1 activity in ECs, and thereby, conditional deletion of S1PR1 in ECs (EC-S1pr1 mice) impairs tumor vascularization and growth. Mechanistically, we show that S1PR1 engages the heterotrimeric G-protein Gi, which amplifies VEGF-VEGFR2 signaling due to an increase in the activity of the tyrosine kinase c-Abl1. c-Abl1, by phosphorylating VEGFR2 at tyrosine-951, prolongs VEGFR2 retention on the plasmalemma to sustain Rac1 activity and EC migration. Thus, S1PR1 or VEGFR2 antagonists, alone or in combination, reverse the tumor growth in control mice to the level seen in EC-S1pr1 mice. Our findings suggest that blocking S1PR1 activity in ECs has the potential to suppress tumor growth by preventing amplification of VEGF-VEGFR2 signaling.
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http://dx.doi.org/10.1016/j.celrep.2019.11.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927555PMC
December 2019