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Author Howard A Young

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Multi-omics: Differential expression of IFN-γ results in distinctive mechanistic features linking chronic inflammation, gut dysbiosis, and autoimmune diseases.

Heekyong R Bae, Patrick S C Leung, Deborah L Hodge, John M Fenimore, Seon-Min Jeon, Vishal Thovarai, Amiran Dzutsev, Andrew A Welcher, Michael Boedigheimer, Michael A Damore, Myung-Sook Choi, Richard A Fravell, Giorgio Trinchieri, M Eric Gershwin, Howard A Young,

Low grade, chronic inflammation is a critical risk factor for immunologic dysfunction including autoimmune diseases. However, the multiplicity of complex mechanisms and lack of relevant murine models limit our understanding of the precise role of chronic inflammation. To address these hurdles, we took advantage of multi-omics data and a unique ... Read more >>

J. Autoimmun. (Journal of Autoimmunity)
[2020, 111:102436]

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Adaptive in vivo device for theranostics of inflammation: Real-time monitoring of interferon-γ and aspirin.

Chaomin Cao, Ronghua Jin, Hui Wei, Zhongning Liu, Shengnan Ni, Guo-Jun Liu, Howard A Young, Xin Chen, Guozhen Liu,

Cytokines mediate and control immune and inflammatory responses. Complex interactions exist among cytokines, inflammation, and the innate and adaptive immune responses in maintaining homeostasis, health, and well-being. On-demand, local delivery of anti-inflammatory drugs to target tissues provides an approach for more effective drug dosing while reducing the adverse effects of ... Read more >>

Acta Biomater (Acta biomaterialia)
[2020, 101:372-383]

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Ion Gresser 1928-2019.

Jan Vilcek, Howard A Young,

Nat. Immunol. (Nature immunology)
[2019, 20(7):775]

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IFN-γ: A cytokine at the right time, is in the right place.

J Daniel Burke, Howard A Young,

Interferon gamma has long been studied as a critical mediator of tumor immunity. In recent years, the complexity of cellular interactions that take place in the tumor microenvironment has become better appreciated in the context of immunotherapy. While checkpoint inhibitors have dramatically improved remission rates in cancer treatment, IFN-γ and ... Read more >>

Semin. Immunol. (Seminars in immunology)
[2019, 43:101280]

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Report on the 2018 Cancer, Autoimmunity, and Immunology Conference.

Colleen S Curran, Connie L Sommers, Howard A Young, Katarzyna Bourcier, Marie Mancini, Elad Sharon,

With the increased use of cancer immunotherapy, a number of immune-related adverse events (irAEs) are being identified. These irAEs can be compared with known autoimmune disorders in similar tissues, with important similarities and differences. Understanding the etiology of irAEs may bring to light concepts applicable to immune responses in cancer, ... Read more >>

J. Immunol. (Journal of immunology (Baltimore, Md. : 1950))
[2019, 202(10):2823-2828]

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Meeting Overview: Interferon Lambda-Disease Impact and Therapeutic Potential.

Thomas R O'Brien, Howard A Young, Raymond P Donnelly, Ludmila Prokunina-Olsson,

A meeting entitled, "Interferon Lambda: Disease Impact and Translational Potential," was held on the campus of the National Institutes of Health in Bethesda, Maryland, on October 25-26, 2018. To our knowledge, this was the first meeting that focused exclusively on interferon lambda (IFN-λ). The meeting's purpose was to enhance interdisciplinary ... Read more >>

J. Interferon Cytokine Res. (Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research)
[2019, 39(10):586-591]

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Durvalumab in Combination with Olaparib in Patients with Relapsed SCLC: Results from a Phase II Study.

Anish Thomas, Rasa Vilimas, Christopher Trindade, Rebecca Erwin-Cohen, Nitin Roper, Liqiang Xi, Venkatesh Krishnasamy, Elliot Levy, Andy Mammen, Samantha Nichols, Yuanbin Chen, Vamsidhar Velcheti, Faye Yin, Eva Szabo, Yves Pommier, Seth M Steinberg, Jane B Trepel, Mark Raffeld, Howard A Young, Javed Khan, Stephen Hewitt, Jung-Min Lee,

PURPOSE:Despite high tumor mutationburden, immune checkpoint blockade has limited efficacy in SCLC. We hypothesized that poly (ADP-ribose) polymerase inhibition could render SCLC more susceptible to immune checkpoint blockade. METHODS:A single-arm, phase II trial (NCT02484404) enrolled patients with relapsed SCLC who received durvalumab, 1500 mg every 4 weeks, and olaparib, 300 ... Read more >>

J Thorac Oncol (Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer)
[2019, 14(8):1447-1457]

Cited: 4 times

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Thymic expression of IL-4 and IL-15 after systemic inflammatory or infectious Th1 disease processes induce the acquisition of "innate" characteristics during CD8+ T cell development.

Natalia S Baez, Fabio Cerbán, Constanza Savid-Frontera, Deborah L Hodge, Jimena Tosello, Eva Acosta-Rodriguez, Laura Almada, Adriana Gruppi, Maria Estefania Viano, Howard A Young, Maria Cecilia Rodriguez-Galan,

Innate CD8+ T cells express a memory-like phenotype and demonstrate a strong cytotoxic capacity that is critical during the early phase of the host response to certain bacterial and viral infections. These cells arise in the thymus and depend on IL-4 and IL-15 for their development. Even though innate CD8+ ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2019, 15(1):e1007456]

Cited: 1 time

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Partners in Crime: Fledgling Tumors Hijack Inflammation.

Balamurugan Kuppusamy, Howard A Young,

J. Interferon Cytokine Res. (Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research)
[2019, 39(1):1-5]

Cited: 0 times

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Critical role of post-transcriptional regulation for IFN-γ in tumor-infiltrating T cells.

Fiamma Salerno, Aurelie Guislain, Julian J Freen-Van Heeren, Benoit P Nicolet, Howard A Young, Monika C Wolkers,

Protective T cell responses against tumors require the production of Interferon gamma (IFN-γ). However, tumor-infiltrating T cells (TILs) gradually lose their capacity to produce IFN-γ and therefore fail to clear malignant cells. Dissecting the underlying mechanisms that block cytokine production is thus key for improving T cell products. Here we ... Read more >>

Oncoimmunology (Oncoimmunology)
[2019, 8(2):e1532762]

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Interferon-Gamma Impairs Maintenance and Alters Hematopoietic Support of Bone Marrow Mesenchymal Stromal Cells.

Marieke Goedhart, Anne S Cornelissen, Carlijn Kuijk, Sulima Geerman, Marion Kleijer, Jaap D van Buul, Stephan Huveneers, Marc H G P Raaijmakers, Howard A Young, Monika C Wolkers, Carlijn Voermans, Martijn A Nolte,

Bone marrow (BM) mesenchymal stromal cells (MSCs) provide microenvironmental support to hematopoietic stem and progenitor cells (HSPCs). Culture-expanded MSCs are interesting candidates for cellular therapies due to their immunosuppressive and regenerative potential which can be further enhanced by pretreatment with interferon-gamma (IFN-γ). However, it remains unknown whether IFN-γ can also ... Read more >>

Stem Cells Dev. (Stem cells and development)
[2018, 27(9):579-589]

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Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions.

Ashley V Menk, Nicole E Scharping, Rebecca S Moreci, Xue Zeng, Cliff Guy, Sonia Salvatore, Heekyong Bae, Jianxin Xie, Howard A Young, Stacy Gelhaus Wendell, Greg M Delgoffe,

To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain unclear. We show T cell activation rapidly induces glycolysis independent of transcription, ... Read more >>

Cell Rep (Cell Reports)
[2018, 22(6):1509-1521]

Cited: 26 times

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The interplay of type I and type II interferons in murine autoimmune cholangitis as a basis for sex-biased autoimmunity.

Heekyong R Bae, Deborah L Hodge, Guo-Xiang Yang, Patrick S C Leung, Sathi Babu Chodisetti, Julio C Valencia, Michael Sanford, John M Fenimore, Ziaur S M Rahman, Koichi Tsuneyama, Gary L Norman, M Eric Gershwin, Howard A Young,

We have reported on a murine model of autoimmune cholangitis, generated by altering the AU-rich element (ARE) by deletion of the interferon gamma (IFN-γ) 3' untranslated region (coined ARE-Del-/- ), that has striking similarities to human primary biliary cholangitis (PBC) with female predominance. Previously, we suggested that the sex bias ... Read more >>

Hepatology (Hepatology (Baltimore, Md.))
[2018, 67(4):1408-1419]

Cited: 4 times

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Therapeutic and immunological interventions in primary biliary cholangitis: from mouse models to humans.

Atsushi Tanaka, Patrick S C Leung, Howard A Young, M Eric Gershwin,

Arch Med Sci (Archives of medical science : AMS)
[2018, 14(4):930-940]

Cited: 0 times

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Current prospects of type II interferon γ signaling and autoimmunity.

Daniel S Green, Howard A Young, Julio C Valencia,

Interferon γ (IFNγ) is a pleiotropic protein secreted by immune cells. IFNγ signals through the IFNγ receptor, a protein complex that mediates downstream signaling events. Studies into IFNγ signaling have provided insight into the general concepts of receptor signaling, receptor internalization, regulation of distinct signaling pathways, and transcriptional regulation. Although ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2017, 292(34):13925-13933]

Cited: 21 times

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Toward solving the etiological mystery of primary biliary cholangitis.

Atsushi Tanakaa, Patrick Sc Leung, Howard A Young, M Eric Gershwin,

Primary biliary cholangitis (PBC) is considered a model autoimmune disease due to its signature AMA autoantibody, female predominance and relatively specific portal infiltration and cholestasis. The identification and cloning of the major mitochondrial autoantigens, recognized by AMA, have served as an immunologic platform to identify the earliest events involved in ... Read more >>

Hepatol Commun (Hepatology communications)
[2017, 1(4):275-287]

Cited: 5 times

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Th1 Differentiation Drives the Accumulation of Intravascular, Non-protective CD4 T Cells during Tuberculosis.

Michelle A Sallin, Shunsuke Sakai, Keith D Kauffman, Howard A Young, Jinfang Zhu, Daniel L Barber,

Recent data indicate that the differentiation state of Th1 cells determines their protective capacity against tuberculosis. Therefore, we examined the role of Th1-polarizing factors in the generation of protective and non-protective subsets of Mtb-specific Th1 cells. We find that IL-12/23p40 promotes Th1 cell expansion and maturation beyond the CD73+CXCR3+T-betdim stage, and ... Read more >>

Cell Rep (Cell Reports)
[2017, 18(13):3091-3104]

Cited: 23 times

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Rapid and Rigorous IL-17A Production by a Distinct Subpopulation of Effector Memory T Lymphocytes Constitutes a Novel Mechanism of Toxic Shock Syndrome Immunopathology.

Peter A Szabo, Ankur Goswami, Delfina M Mazzuca, Kyoungok Kim, David B O'Gorman, David A Hess, Ian D Welch, Howard A Young, Bhagirath Singh, John K McCormick, S M Mansour Haeryfar,

Toxic shock syndrome (TSS) is caused by staphylococcal and streptococcal superantigens (SAgs) that provoke a swift hyperinflammatory response typified by a cytokine storm. The precipitous decline in the host's clinical status and the lack of targeted therapies for TSS emphasize the need to identify key players of the storm's initial ... Read more >>

J. Immunol. (Journal of immunology (Baltimore, Md. : 1950))
[2017, 198(7):2805-2818]

Cited: 4 times

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CD4 T Cell-Derived IFN-γ Plays a Minimal Role in Control of Pulmonary Mycobacterium tuberculosis Infection and Must Be Actively Repressed by PD-1 to Prevent Lethal Disease.

Shunsuke Sakai, Keith D Kauffman, Michelle A Sallin, Arlene H Sharpe, Howard A Young, Vitaly V Ganusov, Daniel L Barber,

IFN-γ-producing CD4 T cells are required for protection against Mycobacterium tuberculosis (Mtb) infection, but the extent to which IFN-γ contributes to overall CD4 T cell-mediated protection remains unclear. Furthermore, it is not known if increasing IFN-γ production by CD4 T cells is desirable in Mtb infection. Here we show that ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2016, 12(5):e1005667]

Cited: 88 times

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Chronic expression of interferon-gamma leads to murine autoimmune cholangitis with a female predominance.

Heekyong R Bae, Patrick S C Leung, Koichi Tsuneyama, Julio C Valencia, Deborah L Hodge, Seohyun Kim, Tim Back, Megan Karwan, Anand S Merchant, Nobuyuki Baba, Dechun Feng, Ogyi Park, Bin Gao, Guo-Xiang Yang, M Eric Gershwin, Howard A Young,

UNLABELLED:In most autoimmune diseases the serologic hallmarks of disease precede clinical pathology by years. Therefore, the use of animal models in defining early disease events becomes critical. We took advantage of a "designer" mouse with dysregulation of interferon gamma (IFNγ) characterized by prolonged and chronic expression of IFNγ through deletion ... Read more >>

Hepatology (Hepatology (Baltimore, Md.))
[2016, 64(4):1189-1201]

Cited: 23 times

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Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers.

Catalina Lee-Chang, Monica Bodogai, Kanako Moritoh, Xin Chen, Robert Wersto, Ranjan Sen, Howard A Young, Michael Croft, Luigi Ferrucci, Arya Biragyn,

B cell dysregulation in aging is thought to mostly occur in conventional B2 cells without affecting innate B1 cells. Elderly humans and mice also accumulate 4-1BBL(+)MHC class-I(Hi)CD86(Hi)B cells of unknown origin. In this article, we report that these cells, termed 4BL cells, are activated murine and possibly human B1a cells. ... Read more >>

J. Immunol. (Journal of immunology (Baltimore, Md. : 1950))
[2016, 196(8):3385-3397]

Cited: 6 times

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Regulation of IFN-γ Expression.

John Fenimore, Howard A Young,

Interferon gamma, referred to here as IFN-γ, is a major component in immunological cell signaling and is a critical regulatory protein for overall immune system function. First discovered in 1965 (Wheelock Science 149: (3681)310-311, 1965), IFN-γ is the only Type II interferon identified. Its expression is both positively and negatively ... Read more >>

Adv. Exp. Med. Biol. (Advances in experimental medicine and biology)
[2016, 941:1-19]

Cited: 2 times

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Surface display of glycosylated Tyrosinase related protein-2 (TRP-2) tumour antigen on Lactococcus lactis.

Jeevanathan Kalyanasundram, Suet Lin Chia, Adelene Ai-Lian Song, Abdul Rahim Raha, Howard A Young, Khatijah Yusoff,

The exploitation of the surface display system of food and commensal lactic acid bacteria (LAB) for bacterial, viral, or protozoan antigen delivery has received strong interest recently. The Generally Regarded as Safe (GRAS) status of the Lactococcus lactis coupled with a non-recombinant strategy of in-trans surface display, provide a safe ... Read more >>

BMC Biotechnol. (BMC biotechnology)
[2015, 15:113]

Cited: 6 times

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Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications.

Ken-ichiro Matsunaga, Michiko Kimoto, Charlotte Hanson, Michael Sanford, Howard A Young, Ichiro Hirao,

We present a remodeling method for high-affinity unnatural-base DNA aptamers to augment their thermal stability and nuclease resistance, for use as drug candidates targeting specific proteins. Introducing a unique mini-hairpin DNA provides robust stability to unnatural-base DNA aptamers generated by SELEX using genetic alphabet expansion, without reducing their high affinity. ... Read more >>

Sci Rep (Scientific reports)
[2015, 5:18478]

Cited: 9 times

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Impact of dietary components on NK and Treg cell function for cancer prevention.

Young S Kim, Thomas J Sayers, Nancy H Colburn, John A Milner, Howard A Young,

An important characteristic of cancer is that the disease can overcome the surveillance of the immune system. A possible explanation for this resistance arises from the ability of tumor cells to block the tumoricidal activity of host immune cells such as natural killer (NK) cells by inducing the localized accumulation ... Read more >>

Mol. Carcinog. (Molecular carcinogenesis)
[2015, 54(9):669-678]

Cited: 6 times

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