scispace - formally typeset
Search or ask a question
Author

Conor Gruber

Bio: Conor Gruber is an academic researcher from Icahn School of Medicine at Mount Sinai. The author has contributed to research in topics: Myeloid & Medicine. The author has an hindex of 11, co-authored 20 publications receiving 1391 citations.
Topics: Myeloid, Medicine, Biology, Immune system, Antigen

Papers
More filters
Journal ArticleDOI
Nicolas Vabret1, Graham J. Britton1, Conor Gruber1, Samarth Hegde1, Joel Kim1, Maria Kuksin1, Rachel Levantovsky1, Louise Malle1, Alvaro Moreira1, Matthew D. Park1, Luisanna Pia1, Emma Risson1, Miriam Saffern1, Bérengère Salomé1, Myvizhi Esai Selvan1, Matthew P. Spindler1, Jessica Tan1, Verena van der Heide1, Jill Gregory1, Konstantina Alexandropoulos1, Nina Bhardwaj1, Brian D. Brown1, Benjamin Greenbaum1, Zeynep H. Gümüş1, Dirk Homann1, Amir Horowitz1, Alice O. Kamphorst1, Maria A. Curotto de Lafaille1, Saurabh Mehandru1, Miriam Merad1, Robert M. Samstein1, Manasi Agrawal, Mark Aleynick, Meriem Belabed, Matthew Brown1, Maria Casanova-Acebes, Jovani Catalan, Monica Centa, Andrew Charap, Andrew K Chan, Steven T. Chen, Jonathan Chung, Cansu Cimen Bozkus, Evan Cody, Francesca Cossarini, Erica Dalla, Nicolas F. Fernandez, John A. Grout, Dan Fu Ruan, Pauline Hamon, Etienne Humblin, Divya Jha, Julia Kodysh, Andrew Leader, Matthew Lin, Katherine E. Lindblad, Daniel Lozano-Ojalvo, Gabrielle Lubitz, Assaf Magen, Zafar Mahmood2, Gustavo Martinez-Delgado, Jaime Mateus-Tique, Elliot Meritt, Chang Moon1, Justine Noel, Timothy O'Donnell, Miyo Ota, Tamar Plitt, Venu Pothula, Jamie Redes, Ivan Reyes Torres, Mark P. Roberto, Alfonso R. Sanchez-Paulete, Joan Shang, Alessandra Soares Schanoski, Maria Suprun, Michelle Tran, Natalie Vaninov, C. Matthias Wilk, Julio A. Aguirre-Ghiso, Dusan Bogunovic1, Judy H. Cho, Jeremiah J. Faith, Emilie K. Grasset, Peter S. Heeger, Ephraim Kenigsberg, Florian Krammer1, Uri Laserson1 
16 Jun 2020-Immunity
TL;DR: The current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death are summarized.

1,350 citations

Journal ArticleDOI
12 Nov 2020-Cell
TL;DR: The auto-antigen reactivity of MIS-C plasma revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens.

396 citations

Posted ContentDOI
06 Jul 2020-medRxiv
TL;DR: To assess the role for autoimmunity secondary to infection, the auto-antigen reactivity of MIS-C plasma was profiled, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens.
Abstract: Initially, the global outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spared children from severe disease However, after the initial wave of infections, clusters of a novel hyperinflammatory disease have been reported in regions with ongoing SARS-CoV-2 epidemics While the characteristic clinical features are becoming clear, the pathophysiology remains unknown Herein, we report on the immune profiles of eight Multisystem Inflammatory Syndrome in Children (MIS-C) cases We document that all MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with normal isotype-switching and neutralization capability We further profiled the secreted immune response by high-dimensional cytokine assays, which identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1) and mucosal immune dysregulation (IL-17A, CCL20, CCL28) Mass cytometry immunophenotyping of peripheral blood revealed reductions of mDC1 and non-classical monocytes, as well as both NK- and T- lymphocytes, suggesting extravasation to affected tissues Markers of activated myeloid function were also evident, including upregulation of ICAM1 and FcR1 in neutrophil and non-classical monocytes, well-documented markers in autoinflammation and autoimmunity that indicate enhanced antigen presentation and Fc-mediated responses Finally, to assess the role for autoimmunity secondary to infection, we profiled the auto-antigen reactivity of MIS-C plasma, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens All patients were treated with anti- IL6R antibody or IVIG, which led to rapid disease resolution tracking with normalization of inflammatory markers

133 citations

Journal ArticleDOI
23 Dec 2020-Cell
TL;DR: Human T-bet deficiency underlies mycobacterial disease by preventing the development of innate (NK) and innate-like adaptive lymphocytes (iNKT, MAIT, and Vδ2+ γδ T cells) and IFN-γ production by them.

77 citations

Journal ArticleDOI
TL;DR: A neonate who presented with hydrocephalus, necrotizing cellulitis, systemic inflammation, and respiratory failure was followed by a prompt and sustained recovery after treatment with ruxolitinib and a homozygous mutation at an essential splice site on USP18 was identified.
Abstract: Deficiency of ubiquitin-specific peptidase 18 (USP18) is a severe type I interferonopathy. USP18 down-regulates type I interferon signaling by blocking the access of Janus-associated kinase 1 (JAK1) to the type I interferon receptor. The absence of USP18 results in unmitigated interferon-mediated inflammation and is lethal during the perinatal period. We describe a neonate who presented with hydrocephalus, necrotizing cellulitis, systemic inflammation, and respiratory failure. Exome sequencing identified a homozygous mutation at an essential splice site on USP18. The encoded protein was expressed but devoid of negative regulatory ability. Treatment with ruxolitinib was followed by a prompt and sustained recovery. (Funded by King Saud University and others.).

62 citations


Cited by
More filters
01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

4,408 citations

Journal ArticleDOI
TL;DR: In this article, the authors describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity.

2,933 citations

01 Jan 2011
TL;DR: The sheer volume and scope of data posed by this flood of data pose a significant challenge to the development of efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data.
Abstract: Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

2,187 citations

Journal ArticleDOI
TL;DR: The first discoveries that shape the current understanding of SARS-CoV-2 infection throughout the intracellular viral life cycle are summarized and relate that to the knowledge of coronavirus biology.
Abstract: The SARS-CoV-2 pandemic and its unprecedented global societal and economic disruptive impact has marked the third zoonotic introduction of a highly pathogenic coronavirus into the human population. Although the previous coronavirus SARS-CoV and MERS-CoV epidemics raised awareness of the need for clinically available therapeutic or preventive interventions, to date, no treatments with proven efficacy are available. The development of effective intervention strategies relies on the knowledge of molecular and cellular mechanisms of coronavirus infections, which highlights the significance of studying virus-host interactions at the molecular level to identify targets for antiviral intervention and to elucidate critical viral and host determinants that are decisive for the development of severe disease. In this Review, we summarize the first discoveries that shape our current understanding of SARS-CoV-2 infection throughout the intracellular viral life cycle and relate that to our knowledge of coronavirus biology. The elucidation of similarities and differences between SARS-CoV-2 and other coronaviruses will support future preparedness and strategies to combat coronavirus infections.

1,787 citations

Journal ArticleDOI
Qian Zhang1, Paul Bastard2, Paul Bastard3, Zhiyong Liu1  +169 moreInstitutions (34)
23 Oct 2020-Science
TL;DR: The COVID Human Genetic Effort established to test the general hypothesis that life-threatening COVID-19 in some or most patients may be caused by monogenic inborn errors of immunity to SARS-CoV-2 with incomplete or complete penetrance finds an enrichment in variants predicted to be loss-of-function (pLOF), with a minor allele frequency <0.001.
Abstract: Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.

1,659 citations