Notre Dame Researchers Invent Trap for Capturing and Comparing Individual Bacterial Cells

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University of Notre Dame
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Notre Dame Researchers Invent Trap for Capturing and Comparing Individual Bacterial Cells
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Genomics—Integrated Research Facility at Fort Detrick

The Genomics team at the IRF-Frederick supports studies, including virus genome sequence analysis, host transcriptome and metagenome analysis, and subpopulation or immune response analysis using single-cell sequencing. The team provides collaborative support for genomic analysis planning, sample preparation, preparation of sequencing libraries, next-generation sequencing using short-read or nanopore-based long-read sequencing, and data analyses.

National and Regional Biocontainment Research Facilities

The National Biocontainment Laboratories (NBLs) and Regional Biocontainment Laboratories (RBLs) provide BSL4/3/2 and BSL3/2 biocontainment facilities, respectively, for research on biodefense and emerging infectious disease agents.  

Genomic Research Integration System (GRIS)

The Genomic Research Integration System (GRIS) Portal provides meaningful collaborative analysis of integrated clinical, family, and genomic data generated from the Clinical Genomics Program and its collaborators’ studies. GRIS streamlines data management for experimental analysis, validation, and reporting workflows to improve productivity, standardization, data integrity, data sharing, and reproducibility.

Why Does COVID-19 Cause Severe Illness in Some Patients but Not Others?

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Yale School of Medicine
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Why Does COVID-19 Cause Severe Illness in Some Patients but Not Others?
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AI Helps Create Better, Simpler Hepatitis, COVID-19 Tests

CRISPR and Single-Cell Sequencing Pinpoint Causal Genetic Variants for Traits and Diseases

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New York University
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CRISPR Single-Cell Sequencing Pinpoint Causal Genetic Variants Traits Diseases
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Sinu P. John, Ph.D.

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Signaling Systems Section
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Program Description

Our research focuses primarily on identification of cell intrinsic factors (protein coding and non-coding genes) associated with regulation of macrophage signaling. We use high throughput genome-wide techniques such as RNAi screening, CRISPR screening, RNA-seq, ATAC-seq, etc. to identify and characterize the genes and gene-regulatory mechanisms that modulate the immune response in macrophage cells. In addition, we study the role of various external factors (environmental pollutants, drugs, diet, etc.) that modulate the immune response in macrophages with an emphasis to develop therapeutic candidates for the treatment of infectious and immune diseases. We use both bacterial and several emerging viral models such as HIV, Influenza, SARS-CoV-2, etc. to study the impact of immune regulation by various intrinsic and external factors.

Selected Publications

John SP, Singh A, Sun J, Pierre MJ, Alsalih L, Lipsey C, Traore Z, Balcom-Luker S, Bradfield CJ, Song J, Markowitz TE, Smelkinson M, Ferrer M, Fraser IDC. Small-molecule screening identifies Syk kinase inhibition and rutaecarpine as modulators of macrophage training and SARS-CoV-2 infection. Cell Rep. 2022 Oct 4;41(1):111441.

John SP, Sun J, Carlson RJ, Cao B, Bradfield CJ, Song J, Smelkinson M, Fraser IDC. IFIT1 Exerts Opposing Regulatory Effects on the Inflammatory and Interferon Gene Programs in LPS-Activated Human Macrophages. Cell Rep. 2018 Oct 2;25(1):95-106.e6.

John SP, Chin CR, Perreira JM, Feeley EM, Aker AM, Savidis G, Smith SE, Elia AE, Everitt AR, Vora M, Pertel T, Elledge SJ, Kellam P, Brass AL. The CD225 domain of IFITM3 is required for both IFITM protein association and inhibition of influenza A virus and dengue virus replication. J Virol. 2013 Jul;87(14):7837-52.

Zhu J, Gaiha GD, John SP, Pertel T, Chin CR, Gao G, Qu H, Walker BD, Elledge SJ, Brass AL. Reactivation of latent HIV-1 by inhibition of BRD4. Cell Rep. 2012 Oct 25;2(4):807-16.

Everitt AR, Clare S, Pertel T, John SP, Wash RS, Smith SE, Chin CR, Feeley EM, Sims JS, Adams DJ, Wise HM, Kane L, Goulding D, Digard P, Anttila V, Baillie JK, Walsh TS, Hume DA, Palotie A, Xue Y, Colonna V, Tyler-Smith C, Dunning J, Gordon SB; GenISIS Investigators; MOSAIC Investigators; Smyth RL, Openshaw PJ, Dougan G, Brass AL, Kellam P. IFITM3 restricts the morbidity and mortality associated with influenza. Nature. 2012 Mar 25;484(7395):519-23.

Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E, Adams DJ, Xavier RJ, Farzan M, Elledge SJ. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell. 2009 Dec 24;139(7):1243-54.

Visit PubMed for a complete publication listing.

Major Areas of Research
  • Genes and epigenetic states modulating macrophage signaling and function
  • Identification and characterization of trained immunity stimuli
  • Applications of trained immunity in infectious and immune disease

Researchers Warn of Tick-Borne Disease Babesiosis

Tick-borne Powassan virus is being transmitted in concentrated clusters in New England, Yale study says

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Yale University
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Tick-borne Powassan virus is being transmitted in concentrated clusters in New England, Yale study says
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