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Laboratory of Human Retrovirology and Immunoinformatics (LHRI)
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Laboratory of Human Retrovirology and Immunoinformatics


1. Mission
2. Research Interest
3. Address
4. Campus Map
5. Ask Questions
6. LHRI Group
1. Mission
The mission of the Laboratory of Human Retrovirology and Immunoinformatics (LHRI) is to investigate the mechanism of immune and viral responses in infected individuals utilizing microbiological, biochemical and immunological techniques, and bioinformatics analysis.
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2. Research Interest
The Laboratory of Human Retrovirology and Immunoinformatics (LHRI) has investigated mechanism of multiple-class drug resistant (MDR) in HIV infection. Goals of the studies are to define salvage therapies for each patient-infected with MDR strains and to develop novel anti-viral therapies for each MDR strain using either chemical compounds (nucleotide, peptides or others) or immune regulatory proteins (cytokines or other proteins). LHRI has cloned multiple MDR strains from the infected patients and profiled drug sensitivity of each strain against FDA approved and experimental drugs in vitro. LHRI has also characterized pathogenesis and innate immune response to MDR infection. LHRI has first reported that Interleukin-27 possesses anti-HIV property and discovered four novel none-coding RNAs as novel anti-viral nucleotides; those are potential anti-MDR reagents. The second LHRI research area is the mechanism of human innate immune response via Ku70, a component of the DNA repair complex protein, as a cytosolic DNA sensor. Upon transfection with DNA or infection with DNA virus, Ku70 in the cytosol detects the invaded DNA and then predominately induces interferon lambda1 (IFN-λ1) rather than IFN-α or IFN-β, through a STING-dependent signaling pathway. Accumulation of cytoplasmic translocation of Ku70 only occurred in DNA-triggered IFN-λ1 inducible cells and enhances the innate immune response. Recently, LHRI found that Herpes Simplex Virus type-1 (DNA virus) infection induces IFN-λ1 via Ku70, but it is strain-dependent; HSV-1 McKrae, but not MacIntyre strain induces IFN-λ1 (Figure 1).


Figure 1. The cytoplasmic translocation of Ku70 in DNA transfected or HSV-1 virus (McKrae and MacIntyre strain) infected HEK cells. The localization of Ku70 was visualized under confocal microscope. HEK cells were seeded on coverslip-inserted 12-well plates, and then were transfected with MFP488-labelled DNA (green) or infected by HSV-1 at MOL of 1.6 h after DNA transfection or 16 h after infection, the cells were fixed and stained with anti-Ku70 (red) antibody or anti-HSV-1 (green) antibody. Nuclei were visualized by DAPI (blue). Original magnification was x40. Scale bar: 10 μm.

The mechanism was further confirmed by that the inhibition of Ku70 translocation also inhibited IFN-λ1 induction, and enhancing the acetylation status of the cells promotes Ku70's cytoplasmic accumulation, increases DNA-mediated IFN-λ1 induction. These findings provide insights into the molecular mechanism by which the versatile sensor detects pathogenic DNA in a localization-dependent manner (Figure 2).


Figure 2. Working model for the cytosolic DNA sensing activity of Ku70. Ku70 undergoes a translocation from the nucleus to the cytoplasm to recognize cytosolic viral DNA or other form of DNA followed by interacting with STING and activating the downstream IFN-λ1 signaling pathway. Acetylation modulates DNA-mediated Ku70-dependent IFN-λ1 induction. Ku80 colocalizes with Ku70 during Ku70 translocation from the nucleus to the cytoplasm, but not directly involving in Ku70's cytosolic DNA activity.

The third research area is to study the host genetic determinants that affect HIV pathogenesis and progression. Genome-wide associate study have identified eleven loci associated with three biomarker levels (six loci known in the general population and five novel loci associated with D-dimer and IL-6 levels) in people living with HIV (PLWH) of three ethnic groups: African (AFR), Admixed American (AMR), European (EUR). Three of them are ethnic specific and other eight loci have been identified by transethnic meta-analyses (Figure 3).


Figure 3. Manhattan plots of transethnic meta-analyses results for genetic associations with three biomarkers. (A). hsCRP levels, (B). D-dimer levels, (C). IL-6 levels. Loci are labeled by the closest genes. Each point represents one SNP and is plotted by chromosomal location (x-axis) and -log10(P) (y-axis). The dashed red line represents genome-wide significance (P = 5 x 10-8) and SNPs meeting this threshold are colored red.

The findings support the hypothesis that host genetics may partially contribute to chronic inflammation in PLWH and help to identify potential targets for intervention of serious non-AIDS complications. LHRI also has a strong bioinformatics team supporting the research in the basic and translational research sections in LHRI, other laboratories in ADRD at Frederick National laboratory, NIAID and other NIH institutes. The bioinformatics team is also responsible for updating and maintaining the Database for Annotation, Visualization and Integrated Discovery (DAVID), an important bioinformatics resource system.
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3. Address
310 Wood Street
Building 315, Room 8
Laboratory of Human Retrovirology and Immunoinformatics
Applied/Developmental Research Directorate
Frederick National Laboratory for Cancer Research
Frederick, MD 21702
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4. Campus Map
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5. Ask Questions
DAVID Bioinformatics Questions? Contact the DAVID Bioinformatic Team
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6. LHRI Group


Laboratory of Human Retrovirology and Immunoinformatics (LHRI)

Tomozumi Imamichi, Ph.D.
Sr. Principal Investigator
timamichi@mail.nih.gov
(301) 846-5450
Basic Research Translational Research Bioinformatics
Hongyan Sui, Ph.D.
Scientist II

Suranjana Goswami, Ph.D.
Scientist I

Qian Chen, M.D.
Research Associate III

Jun Yang, M.S.
Bioinformatics Analyst V

Two Postdoctoral Positions Available



Sylvain Laverdure, Ph.D.
Scientist I

Francesca Scrimieri, Ph.D.
Scientist I

Sharada Paudel, Ph.D.
Research Associate II

Whitney Bruchey, B.S.
Research Associate II





Weizhong Chang, Ph.D.
Sr. Bioinformatics Scientist
weizhong.chang@nih.gov
(301) 846-6295

Brad T Sherman, M.S.
IT Manager I

Xiaoli Jiao, Ph.D.
Computational Scientist

Ming Hao, Ph.D.
Bioinformatics Analyst III

Ju Qiu, M.S.
Bioinformatics Analyst II
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Last edited on February 22, 2021



 Please cite Nature Protocols 2009; 4(1):44 & Nucleic Acids Res. 2009;37(1):1 within any publication that makes use of any methods inspired by DAVID.
                                            
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