Papers by Gabriele Grunig
American Journal of Respiratory and Critical Care Medicine
A striking aspect of COVID-19 is the difference in the outcome of the infection between different... more A striking aspect of COVID-19 is the difference in the outcome of the infection between different countries, and different ethnic groups within one country. We surveyed the literature on SARS-CoV-2 complemented with comparative publications on SARS-CoV and other coronaviruses to capture the current understanding of virus – host interactions including virus subtypes, transmission, zoonotic aspects, and potential host determinants.
Frontiers in Physiology
Rationale: Therapeutic exercise training has been shown to significantly improve pulmonary hypert... more Rationale: Therapeutic exercise training has been shown to significantly improve pulmonary hypertension (PH), including 6-min walking distance and right heart function. Supplemental nightly oxygen also has therapeutic effects. A biomarker tool that could query critical gene networks would aid in understanding the molecular effects of the interventions.
American Journal of Respiratory and Critical Care Medicine
Circulation research, Jan 27, 2017
Lung and Blood institute (NHLBI) launched an initiative, PVDOMICS (Redefining Pulmonary Hypertens... more Lung and Blood institute (NHLBI) launched an initiative, PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) that aims to augment the current pulmonary hypertension (PH) classification based on shared biological features. PVDOMICS will enroll 1500 participants with PH and disease and healthy comparators. Enrollees will undergo deep clinical phenotyping, and blood will be acquired for comprehensive omic analyses that will focus on discovery of molecular-based subtypes of pulmonary vascular disease (PVD) through application of high dimensional model-based clustering methods. In addition to an updated, molecular classification of PVD, the phenomic data generated will be a rich resource to the broad community of heart and lung disease investigators. Editorial, see p 1106 PH is a hemodynamic condition that causes increased blood pressure in the pulmonary arteries and the right heart leading to adverse clinical outcomes. The current World Symposium on Pulmonary Hypertension (WSPH) classification of PH is based on a combination of patient characteristics, clinical features, and cardiopulmonary hemodynamics, and these features are used to inform treatment options. 1 Aside from heritable pulmonary arterial hypertension, this classification is not tied to molecular or cellular pathobiologic mechanism to explain the pathogenesis of PH. The NIH has a vested interest in understanding the causes and natural history of PH, as well as the discovery of effective treatment options. Since the first large NIH registry of patients with pulmonary arterial hypertension >30 years ago, 2 significant advances in scientific knowledge and translational medicine have occurred, highlighting a need for updating the current clinical classification system. The NHLBI has sponsored several workshops focusing on PVD research strategic planning over the past decade. PVD encompasses PH and PVD without PH, for example, pulmonary vasculitis and pathological pulmonary vascular remodeling without hemodynamic criteria for PH. Experts identified the need for aggressive genotype-phenotype characterization of PVD and incorporation of systems biology approaches to identify previously unrecognized relationships at a molecular, cellular, or clinical level and to identify potential subjects for appropriate clinical studies. 3,4 A workshop convened by the American Thoracic Society (ATS) had similar recommendations. 5 Both the NIH and ATS workshops highlighted the recent rapid advances in the mechanistic understanding of PVD, improved imaging techniques, omics (hereafter referred to as-omic) technologies, and novel methods for biomarker discovery that present a unique opportunity for clinicians and scientists working jointly to augment PH classification on the basis of these new metrics. In response to the identified opportunities for improved PVD research and treatment, a new PVD initiative from the Division of Lung Diseases was launched in 2014 by the NHLBI. Called PVDOMICS, this program (RFA-HL-14-027 and RFA-HL-14-030) supports a national team of multidisciplinary investigators to perform comprehensive, deep phenotyping across groups 1 to 5 PH. A Data Coordinating Center (Cleveland Clinic) and 6 clinical centers (Brigham and
EBioMedicine, 2016
Gaucher disease (GD), the most common lysosomal storage disease, is caused by mutations in GBA1 e... more Gaucher disease (GD), the most common lysosomal storage disease, is caused by mutations in GBA1 encoding of β-glucocerebrosidase (GCase). Recently it was reported that progranulin (PGRN) insufficiency and deficiency associated with GD in human and mice, respectively. However the underlying mechanisms remain unknown. Here we report that PGRN binds directly to GCase and its deficiency results in aggregation of GCase and its receptor LIMP2. Mass spectrometry approaches identified HSP70 as a GCase/LIMP2 complex-associated protein upon stress, with PGRN as an indispensable adaptor. Additionally, 98 amino acids of C-terminal PGRN, referred to as Pcgin, are required and sufficient for the binding to GCase and HSP70. Pcgin effectively ameliorates the disease phenotype in GD patient fibroblasts and animal models. These findings not only demonstrate that PGRN is a co-chaperone of HSP70 and plays an important role in GCase lysosomal localization, but may also provide new therapeutic interventi...
EBioMedicine, Jan 4, 2016
Gaucher disease (GD) is a genetic disease caused by mutations in the GBA1 gene which result in re... more Gaucher disease (GD) is a genetic disease caused by mutations in the GBA1 gene which result in reduced enzymatic activity of β-glucocerebrosidase (GCase). This study identified the progranulin (PGRN) gene (GRN) as another gene associated with GD. Serum levels of PGRN were measured from 115 GD patients and 99 healthy controls, whole GRN gene from 40 GD patients was sequenced, and the genotyping of 4 SNPs identified in GD patients was performed in 161 GD and 142 healthy control samples. Development of GD in PGRN-deficient mice was characterized, and the therapeutic effect of rPGRN on GD analyzed. Serum PGRN levels were significantly lower in GD patients (96.65±53.45ng/ml) than those in healthy controls of the general population (164.99±43.16ng/ml, p<0.0001) and of Ashkenazi Jews (150.64±33.99ng/ml, p<0.0001). Four GRN gene SNPs, including rs4792937, rs78403836, rs850713, and rs5848, and three point mutations, were identified in a full-length GRN gene sequencing in 40 GD patients...
Chest, 2003
... Janice Hwang, BS; David Yen, BS; Thomas Tschernig, MD; Donna Rennick, PhD; and Gabriele Gruni... more ... Janice Hwang, BS; David Yen, BS; Thomas Tschernig, MD; Donna Rennick, PhD; and Gabriele Grunig, DVM, PhD ... The changes include attraction and differentiation of mast cell precursors, proliferation, attraction, and activation of eosinophils, and IgE production by B cells. ...
The Journal of Immunology, Apr 1, 2011
The Journal of Immunology, Apr 1, 2007
Biology of Reproduction, 1995
The distribution of four cytokines was analyzed in the endometrium and trophoblast of the horse b... more The distribution of four cytokines was analyzed in the endometrium and trophoblast of the horse between Days 30 and 55 of gestation. Endometrial tissues, invasive trophoblast (chorionic girdle), and noninvasive trophoblast (chorion and allantochorion) were examined separately. Cytokine expression was determined by amplification of specific mRNA via the reverse transcriptase-polymerase chain reaction (RT-PCR). Messenger RNA for interleukin 2 (IL-2), interleukin 4 (IL-4), and interferon y (IFNy) was detected in endometrial tissues, unstimulated peripheral blood lymphocytes, and control kidney tissue, but not in trophoblasts. Leukocytes resident in the endometrium or traversing the uterus via blood vessels might be the source of these cytokines. Endometrial tissues and invasive and noninvasive trophoblasts expressed mRNA for tumor necrosis factor a (TNFa). Immunoreactive TNFa protein was detected in different cell types of the endometrium and in the invasive and noninvasive trophoblast. The ubiquitous expression of TNFa by the endometrium and trophoblasts suggests that this cytokine might have an important role in regulating placental growth and differentiation or maternal leukocyte responses to trophoblasts. IL-2, IL-4, and IFNy might have important immunoregulatory roles within the endometrium.
Veterinary Immunology and Immunopathology, Jul 31, 1994
The regulatory effects of phorbol myristate acetate (PMA) on the expression of the CD4 molecule o... more The regulatory effects of phorbol myristate acetate (PMA) on the expression of the CD4 molecule on horse T cells were investigated. On both peripheral blood lymphocytes and thymocytes, PMA resulted in a rapid and transient down-regulation of equine CD4 expression, but had no such effect on the surface expression of equine CD5, CD8 or major histocompatibility complex (MHC) class I and class II molecules. Over 75% of the surface CD4 molecules per cell were lost after a 4 h exposure to PMA at 37 degrees C. The regulation of equine CD4 expression induced by PMA was temperature dependent and reversible. The PMA-mediated loss of CD4 expression was inhibited at 4 degrees C. After 24 h of exposure to PMA, CD4 molecules were re-expressed on the cell surface, even in the continued presence of PMA. These findings demonstrate that equine CD4+ T cells undergo alterations in CD4 expression in response to PMA, and suggest that the equine homolog of the CD4 molecule is regulated by PMA in a similar manner to the human CD4 molecule.
The Journal of Immunology, May 1, 2014
The Faseb Journal, Mar 1, 2008
Biomarker Insights, 2016
This review discusses biomarkers that are being researched for their usefulness to phenotype chro... more This review discusses biomarkers that are being researched for their usefulness to phenotype chronic inflammatory lung diseases that cause remodeling of the lung's architecture. The review focuses on asthma, chronic obstructive pulmonary disease (COPD), and pulmonary hypertension. Biomarkers of environmental exposure and specific classes of biomarkers (noncoding RNA, metabolism, vitamin, coagulation, and microbiome related) are also discussed. Examples of biomarkers that are in clinical use, biomarkers that are under development, and biomarkers that are still in the research phase are discussed. We chose to present examples of the research in biomarker development by diseases, because asthma, COPD, and pulmonary hypertension are distinct entities, although they clearly share processes of inflammation and remodeling.
The Journal of Immunology, Apr 1, 2010
The Journal of Immunology, May 1, 2012
B31. ENVIRONMENTAL EXPOSURES THAT INFLUENCE LUNG FUNCTION, 2012
PloS one, 2015
Air pollution is known to exacerbate chronic inflammatory conditions of the lungs including pulmo... more Air pollution is known to exacerbate chronic inflammatory conditions of the lungs including pulmonary hypertension, cardiovascular diseases and autoimmune diseases. Directly pathogenic antibodies bind pro-inflammatory cell receptors and cause or exacerbate inflammation. In contrast, anti-inflammatory antibody isotypes (e.g. mouse immunoglobulin G1, IgG1) bind inhibitory cell receptors and can inhibit inflammation. Our previous studies showed that co-exposure to antigen and urban ambient particulate matter (PM2.5) induced severe pulmonary arterial thickening and increased right ventricular systolic pressures in mice via T-cell produced cytokines, Interleukin (IL)-13 and IL-17A. The aim of the current study was to understand how B cell and antibody responses integrate into this T cell cytokine network for the pulmonary hypertension phenotype. Special focus was on antigen-specific IgG1 that is the predominant antibody in the experimental response to antigen and urban ambient PM2.5. Wil...
Uploads
Papers by Gabriele Grunig