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  1. Article: Cell-free Chromatin Immunoprecipitation to detect molecular pathways in Physiological and Disease States.

    Jang, Moon K / Markowitz, Tovah E / Andargie, Temesgen E / Apalara, Zainab / Kuhn, Skyler / Agbor-Enoh, Sean

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Patient monitoring is a cornerstone in clinical practice to define disease phenotypes and guide clinical management. Unfortunately, this is often reliant on invasive and/or less sensitive methods that do not provide deep phenotype assessments of disease ... ...

    Abstract Patient monitoring is a cornerstone in clinical practice to define disease phenotypes and guide clinical management. Unfortunately, this is often reliant on invasive and/or less sensitive methods that do not provide deep phenotype assessments of disease state to guide treatment. This paper examined plasma cell-free DNA chromatin immunoprecipitation sequencing (cfChIP-seq) to define molecular gene sets in physiological and heart transplant patients taking immunosuppression medications. We show cfChIP-seq reliably detect gene signals that correlate with gene expression. In healthy controls and in heart transplant patients, cfChIP-seq reliably detected housekeeping genes. cfChIP-seq identified differential gene signals of the relevant immune and non-immune molecular pathways that were predominantly downregulated in immunosuppressed heart transplant patients compared to healthy controls. cfChIP-seq also identified tissue sources of cfDNA, detecting greater cell-free DNA from cardiac, hematopoietic, and other non-hematopoietic tissues such as the pulmonary, digestive, and neurological tissues in transplant patients than healthy controls. cfChIP-seq gene signals were reproducible between patient populations and blood collection methods. cfChIP-seq may therefore be a reliable approach to provide dynamic assessments of molecular pathways and tissue injury associated to disease.
    Language English
    Publishing date 2023-01-25
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.24.525414
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cell-free chromatin immunoprecipitation to detect molecular pathways in heart transplantation.

    Jang, Moon Kyoo / Markowitz, Tovah E / Andargie, Temesgen E / Apalara, Zainab / Kuhn, Skyler / Agbor-Enoh, Sean

    Life science alliance

    2023  Volume 6, Issue 12

    Abstract: Existing monitoring approaches in heart transplantation lack the sensitivity to provide deep molecular assessments to guide management, or require endomyocardial biopsy, an invasive and blind procedure that lacks the precision to reliably obtain biopsy ... ...

    Abstract Existing monitoring approaches in heart transplantation lack the sensitivity to provide deep molecular assessments to guide management, or require endomyocardial biopsy, an invasive and blind procedure that lacks the precision to reliably obtain biopsy samples from diseased sites. This study examined plasma cell-free DNA chromatin immunoprecipitation sequencing (cfChIP-seq) as a noninvasive proxy to define molecular gene sets and sources of tissue injury in heart transplant patients. In healthy controls and in heart transplant patients, cfChIP-seq reliably detected housekeeping genes. cfChIP-seq identified differential gene signals of relevant immune and nonimmune molecular pathways that were predominantly down-regulated in immunosuppressed heart transplant patients compared with healthy controls. cfChIP-seq also identified cell-free DNA tissue sources. Compared with healthy controls, heart transplant patients demonstrated greater cell-free DNA from tissue types associated with heart transplant complications, including the heart, hematopoietic cells, lungs, liver, and vascular endothelium. cfChIP-seq may therefore be a reliable approach to profile dynamic assessments of molecular pathways and sources of tissue injury in heart transplant patients.
    MeSH term(s) Humans ; Heart Transplantation ; Chromatin Immunoprecipitation ; Heart ; Chromatin Immunoprecipitation Sequencing ; Cell-Free Nucleic Acids/genetics
    Chemical Substances Cell-Free Nucleic Acids
    Language English
    Publishing date 2023-09-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ISSN 2575-1077
    ISSN (online) 2575-1077
    DOI 10.26508/lsa.202302003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Racial Differences in Donor-Derived Cell-Free DNA and Mitochondrial DNA After Heart Transplantation, on Behalf of the GRAfT Investigators.

    Shah, Palak / Agbor-Enoh, Sean / Lee, Seiyon / Andargie, Temesgen E / Sinha, Shashank S / Kong, Hyesik / Henry, Lawrence / Park, Woojin / McNair, Erick / Tchoukina, Inna / Shah, Keyur B / Najjar, Samer S / Hsu, Steven / Rodrigo, Maria E / Jang, Moon Kyoo / Marboe, Charles / Berry, Gerald J / Valantine, Hannah A

    Circulation. Heart failure

    2024  Volume 17, Issue 4, Page(s) e011160

    Abstract: Background: Black heart transplant patients are at higher risk of acute rejection (AR) and death than White patients. We hypothesized that this risk may be associated with higher levels of donor-derived cell-free DNA (dd-cfDNA) and cell-free ... ...

    Abstract Background: Black heart transplant patients are at higher risk of acute rejection (AR) and death than White patients. We hypothesized that this risk may be associated with higher levels of donor-derived cell-free DNA (dd-cfDNA) and cell-free mitochondrial DNA.
    Methods: The Genomic Research Alliance for Transplantation is a multicenter, prospective, longitudinal cohort study. Sequencing was used to quantitate dd-cfDNA and polymerase chain reaction to quantitate cell-free mitochondrial DNA in plasma. AR was defined as ≥2R cellular rejection or ≥1 antibody-mediated rejection. The primary composite outcome was AR, graft dysfunction (left ventricular ejection fraction <50% and decrease by ≥10%), or death.
    Results: We included 148 patients (65 Black patients and 83 White patients), median age was 56 years and 30% female sex. The incidence of AR was higher in Black patients compared with White patients (43% versus 19%;
    Conclusions: Elevated dd-cfDNA and cell-free mitochondrial DNA after heart transplant may mechanistically be implicated in the higher incidence of AR and worse clinical outcomes in Black transplant recipients.
    Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.
    MeSH term(s) Humans ; Female ; Middle Aged ; Male ; DNA, Mitochondrial/genetics ; Cell-Free Nucleic Acids/genetics ; Longitudinal Studies ; Prospective Studies ; Race Factors ; Stroke Volume ; Biomarkers ; Graft Rejection/genetics ; Ventricular Function, Left ; Heart Failure/genetics ; Heart Failure/surgery ; Heart Transplantation/adverse effects ; Tissue Donors
    Chemical Substances DNA, Mitochondrial ; Cell-Free Nucleic Acids ; Biomarkers
    Language English
    Publishing date 2024-02-20
    Publishing country United States
    Document type Multicenter Study ; Journal Article
    ZDB-ID 2429459-7
    ISSN 1941-3297 ; 1941-3289
    ISSN (online) 1941-3297
    ISSN 1941-3289
    DOI 10.1161/CIRCHEARTFAILURE.123.011160
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Cell-Free DNA Maps Tissue Injury and Correlates with Disease Severity in Lung Transplant Candidates.

    Balasubramanian, Shanti / Richert, Mary E / Kong, Hyesik / Fu, Sheng / Jang, Moon Kyoo / Andargie, Temesgen E / Keller, Michael B / Alnababteh, Muhtadi / Park, Woojin / Apalara, Zainab / Sun, Jian / Redekar, Neelam / Orens, Jonathan / Aryal, Shambhu / Bush, Errol L / Cantu, Edward / Diamond, Joshua / Shah, Pali / Yu, Kai /
    Nathan, Steven D / Agbor-Enoh, Sean

    American journal of respiratory and critical care medicine

    2023  Volume 209, Issue 6, Page(s) 727–737

    Abstract: Rationale: ...

    Abstract Rationale:
    MeSH term(s) Humans ; Prospective Studies ; Cell-Free Nucleic Acids ; Primary Graft Dysfunction ; Retrospective Studies ; Lung Transplantation ; Patient Acuity
    Chemical Substances Cell-Free Nucleic Acids
    Language English
    Publishing date 2023-12-20
    Publishing country United States
    Document type Multicenter Study ; Journal Article
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.202306-1064OC
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Emergency myelopoiesis distinguishes multisystem inflammatory syndrome in children from pediatric severe COVID-19.

    Roznik, Katerina / Andargie, Temesgen E / Johnston, T Scott / Gordon, Oren / Wang, Yi / Peart Akindele, Nadine / Persaud, Deborah / Antar, Annukka A R / Manabe, Yukari C / Zhou, Weiqiang / Ji, Hongkai / Agbor-Enoh, Sean / Karaba, Andrew H / Thompson, Elizabeth A / Cox, Andrea L

    The Journal of infectious diseases

    2024  

    Abstract: Background: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition caused by recent SARS-CoV-2 infection, but the underlying immunological mechanisms driving this distinct syndrome are unknown.: Methods: We utilized ... ...

    Abstract Background: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition caused by recent SARS-CoV-2 infection, but the underlying immunological mechanisms driving this distinct syndrome are unknown.
    Methods: We utilized high dimensional flow cytometry, cell-free (cf) DNA, and cytokine and chemokine profiling to identify mechanisms of critical illness distinguishing MIS-C from severe acute COVID-19 (SAC).
    Results: Compared to SAC, MIS-C patients demonstrated profound innate immune cell death and features of emergency myelopoiesis (EM), an understudied phenomenon observed in severe inflammation. EM signatures were characterized by fewer mature myeloid cells in the periphery and decreased expression of HLA-DR and CD86 on antigen presenting cells. IL-27, a cytokine known to drive hematopoietic stem cells towards EM, was increased in MIS-C, and correlated with immature cell signatures in MIS-C. Upon recovery, EM signatures decreased, and IL-27 plasma levels returned to normal levels. Despite profound lymphopenia, we report a lack of cfDNA released by adaptive immune cells and increased CCR7 expression on T cells indicative of egress out of peripheral blood.
    Conclusions: Immune cell signatures of EM combined with elevated innate immune cell-derived cfDNA levels distinguish MIS-C from SAC in children and provide mechanistic insight into dysregulated immunity contributing towards MIS-C, offering potential diagnostic and therapeutic targets.
    Language English
    Publishing date 2024-01-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiae032
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Chronic graft-versus-host disease is characterized by high levels and distinctive tissue-of-origin patterns of cell-free DNA.

    Pang, Yifan / Andargie, Temesgen E / Jang, Moon Kyoo / Kong, Hyesik / Park, Woojin / Hill, Thomas / Redekar, Neelam / Fu, Yi-Ping / Parth, Desai A / Holtzman, Noa G / Pavletic, Steven Z / Agbor-Enoh, Sean

    iScience

    2023  Volume 26, Issue 11, Page(s) 108160

    Abstract: Chronic graft-versus-host disease (cGvHD) is a devastating complication of hematopoietic stem cell transplantation (HSCT). Effective early detection may improve the outcome of cGvHD. The potential utility of circulating cell-free DNA (cfDNA), a sensitive ...

    Abstract Chronic graft-versus-host disease (cGvHD) is a devastating complication of hematopoietic stem cell transplantation (HSCT). Effective early detection may improve the outcome of cGvHD. The potential utility of circulating cell-free DNA (cfDNA), a sensitive marker for tissue injury, in HSCT and cGvHD remains to be established. Here, cfDNA of prospectively collected plasma samples from HSCT recipients (including both cGvHD and non-cGvHD) and healthy control (HC) subjects were evaluated. Deconvolution methods utilizing tissue-specific DNA methylation signatures were used to determine cfDNA tissue-of-origin. cfDNA levels were significantly higher in HSCT recipients than HC and significantly higher in cGvHD than non-cGvHD. cGvHD was characterized by a high level of cfDNA from innate immune cells, heart, and liver. Non-hematologic tissue-derived cfDNA was significantly higher in cGvHD than non-cGvHD. cfDNA temporal dynamics and tissue-of-origin composition have distinctive features in patients with cGvHD, supporting further exploration of the utility of cfDNA in the study of cGvHD.
    Language English
    Publishing date 2023-11-02
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.108160
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Cell-free DNA reveals distinct pathology of multisystem inflammatory syndrome in children.

    Andargie, Temesgen E / Roznik, Katerina / Redekar, Neelam / Hill, Tom / Zhou, Weiqiang / Apalara, Zainab / Kong, Hyesik / Gordon, Oren / Meda, Rohan / Park, Woojin / Johnston, Trevor S / Wang, Yi / Brady, Sheila / Ji, Hongkai / Yanovski, Jack A / Jang, Moon K / Lee, Clarence M / Karaba, Andrew H / Cox, Andrea L /
    Agbor-Enoh, Sean

    The Journal of clinical investigation

    2024  Volume 134, Issue 1

    Language English
    Publishing date 2024-01-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI178008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Drebrin 1 in dendritic cells regulates phagocytosis and cell surface receptor expression through recycling for efficient antigen presentation.

    Elizondo, Diana M / Andargie, Temesgen E / Haddock, Naomi L / Boddie, Thomas A / Lipscomb, Michael W

    Immunology

    2018  Volume 156, Issue 2, Page(s) 136–146

    Abstract: Phagocytosis, macropinocytosis and antigen presentation by dendritic cells (DC) requires reorganization of the actin cytoskeleton. Drebrin (Dbn1) is an actin binding and stabilizing protein with roles in endocytosis, formation of dendrite spines in ... ...

    Abstract Phagocytosis, macropinocytosis and antigen presentation by dendritic cells (DC) requires reorganization of the actin cytoskeleton. Drebrin (Dbn1) is an actin binding and stabilizing protein with roles in endocytosis, formation of dendrite spines in neurons and coordinating cell-cell synapses in immune cells. However, its role in DC phagocytosis and antigen presentation is unknown. These studies now report that silencing of Dbn1 in DC resulted in restrained cell surface display of receptors, most notably MHC class I and II and co-stimulatory molecules. This, as expected, resulted in impaired antigen-specific T-cell activation and proliferation. Studies additionally revealed that knockdown of Dbn1 in DC impaired macropinocytosis and phagocytosis. However, there was a concomitant increase in fluid-phase uptake, suggesting that Dbn1 is responsible for the differential control of macropinocytosis versus micropinocytosis activities. Taken together, these findings now reveal that Dbn1 plays a major role in coordinating the actin cytoskeletal activities responsible for antigen presentation in DC.
    MeSH term(s) Animals ; Antigen Presentation ; Cytoskeleton/genetics ; Cytoskeleton/immunology ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Gene Expression Regulation/immunology ; Gene Knockout Techniques ; Histocompatibility Antigens Class I/genetics ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Antigens Class II/genetics ; Histocompatibility Antigens Class II/immunology ; Immunological Synapses/genetics ; Immunological Synapses/immunology ; Lymphocyte Activation/genetics ; Mice ; Mice, Transgenic ; Neuropeptides/genetics ; Neuropeptides/immunology ; Phagocytosis ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology
    Chemical Substances Histocompatibility Antigens Class I ; Histocompatibility Antigens Class II ; Neuropeptides ; drebrins
    Language English
    Publishing date 2018-11-08
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 80124-0
    ISSN 1365-2567 ; 0019-2805 ; 0953-4954
    ISSN (online) 1365-2567
    ISSN 0019-2805 ; 0953-4954
    DOI 10.1111/imm.13010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Inhibition of Allograft Inflammatory Factor-1 in Dendritic Cells Restrains CD4

    Elizondo, Diana M / Andargie, Temesgen E / Yang, Dazhi / Kacsinta, Apollo D / Lipscomb, Michael W

    Frontiers in immunology

    2017  Volume 8, Page(s) 1502

    Abstract: Allograft inflammatory factor-1 (AIF1) is a cytoplasmic scaffold protein shown to influence immune responses in macrophages and microglial cells. The protein contains ... ...

    Abstract Allograft inflammatory factor-1 (AIF1) is a cytoplasmic scaffold protein shown to influence immune responses in macrophages and microglial cells. The protein contains Ca
    Language English
    Publishing date 2017-11-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2017.01502
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Cell-free DNA reveals distinct pathology of multisystem inflammatory syndrome in children.

    Andargie, Temesgen E / Roznik, Katerina / Redekar, Neelam / Hill, Tom / Zhou, Weiqiang / Apalara, Zainab / Kong, Hyesik / Gordon, Oren / Meda, Rohan / Park, Woojin / Johnston, Trevor S / Wang, Yi / Brady, Sheila / Ji, Hongkai / Yanovski, Jack A / Jang, Moon K / Lee, Clarence M / Karaba, Andrew H / Cox, Andrea L /
    Agbor-Enoh, Sean

    The Journal of clinical investigation

    2023  Volume 133, Issue 21

    Abstract: Multisystem inflammatory syndrome in children (MIS-C) is a rare but life-threatening hyperinflammatory condition induced by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes pediatric COVID-19 (pCOVID-19). The ... ...

    Abstract Multisystem inflammatory syndrome in children (MIS-C) is a rare but life-threatening hyperinflammatory condition induced by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes pediatric COVID-19 (pCOVID-19). The relationship of the systemic tissue injury to the pathophysiology of MIS-C is poorly defined. We leveraged the high sensitivity of epigenomics analyses of plasma cell-free DNA (cfDNA) and plasma cytokine measurements to identify the spectrum of tissue injury and glean mechanistic insights. Compared with pediatric healthy controls (pHCs) and patients with pCOVID-19, patients with MIS-C had higher levels of cfDNA primarily derived from innate immune cells, megakaryocyte-erythroid precursor cells, and nonhematopoietic tissues such as hepatocytes, cardiac myocytes, and kidney cells. Nonhematopoietic tissue cfDNA levels demonstrated significant interindividual variability, consistent with the heterogenous clinical presentation of MIS-C. In contrast, adaptive immune cell-derived cfDNA levels were comparable in MIS-C and pCOVID-19 patients. Indeed, the cfDNA of innate immune cells in patients with MIS-C correlated with the levels of innate immune inflammatory cytokines and nonhematopoietic tissue-derived cfDNA, suggesting a primarily innate immunity-mediated response to account for the multisystem pathology. These data provide insight into the pathogenesis of MIS-C and support the value of cfDNA as a sensitive biomarker to map tissue injury in MIS-C and likely other multiorgan inflammatory conditions.
    MeSH term(s) Humans ; Child ; COVID-19/genetics ; SARS-CoV-2 ; Cell-Free Nucleic Acids/genetics ; Cytokines
    Chemical Substances Cell-Free Nucleic Acids ; Cytokines
    Language English
    Publishing date 2023-11-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI171729
    Database MEDical Literature Analysis and Retrieval System OnLINE

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