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Principal Investigator: Yu Zuo
Organization: UNIVERSITY OF MICHIGAN AT ANN ARBOR
Fiscal Year: 2024
Award: $172,800
Funding agency: National Institute of Arthritis and Musculoskeletal and Skin Diseases
PROJECT SUMMARY/ABSTRACT
A growing body of evidence suggests that COVID-19 emulates many aspects of inflammatory and autoimmune
diseases. Circulating autoantibodies have been detected in serum of COVID-19 patients where they have an
antigen profile reminiscent of the lupus-associated thrombophilia known as antiphospholipid syndrome. While
the association between infection, critical illness, and the induction of autoantibodies has long been
recognized, pathogenesis and persistence of these antibodies—and most importantly the extent to which they
may be therapeutic targets—have not been well defined. This award will play a critical role in helping me
achieve my long-term career goals, which include: (1) Establishing a unique niche in the area of infection-
associated autoimmunity; (2) Becoming an independent investigator at a leading medical research institution;
and (3) Mentoring and fostering the development of trainees. These objectives will be reached by incorporating
both a strong mentorship environment and a formal instructional plan.
Mentorship Environment: I am currently an Assistant Professor in the Division of Rheumatology at the
University of Michigan with 75% of my effort protected for research. Over the past two years, I have received
strong training from Dr. Jason Knight in antiphospholipid syndrome pathogenesis. With this proposal, I am
seeking support for a new research endeavor, as I turn my attention to the thromboinflammatory
consequences of infection-associated autoimmunity. I have assembled a strong team of advisors, all experts in
their respective fields and carefully selected to compliment the proposed project and career development.
Formal Instruction: My scientific goals for this proposal include: (1) To expertly assess relevant measures of
thromboinflammation; (2) To effectively manipulate and characterize mouse models; and (3) To develop
laboratory skills in support of the study of autoantibodies and NETs in sepsis. Equally important are my career
development goals, which include: (1) To learn to write innovative proposals in support of ethically-conducted
research in humans and animals; (2) To enhance leadership, mentoring, and team-building skills; and (3) To
continue to improve my written and oral communication. These goals will be achieved through a combination of
mentorship, formal didactic instruction, and experimentation.
Research: I plan to use COVID-19 and other severe infections as a window into the origins of autoimmunity
and—in doing so—determine thromboinflammatory mechanisms of infection-associated autoantibodies. Aim 1
will elucidate the durability and clinical interactions of antiphospholipid antibodies and anti-NET antibodies in
patients hospitalized with either COVID-19 or non-COVID sepsis. Aim 2 will characterize pathogenic and
protective functions of infection-associated autoantibodies.
Terms: <19S Gamma Globulin><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><7S Gamma Globulin><Acceleration><Adhesives><Alveolar><Animal Experimental Use><Animal Experimentation><Animal Research><Animals><Anti-Phospholipid Antibody Syndrome><Anti-phospholipid Syndrome><Antibodies><Antigens><Antiphospholipid Antibodies><Area><Attention><Autoantibodies><Autoimmune Diseases><Autoimmune Status><Autoimmunity><Award><Bacteria><Blood><Blood Neutrophil><Blood Platelets><Blood Polymorphonuclear Neutrophil><Blood Reticuloendothelial System><Blood Serum><Blood Vessels><COVID infected patient><COVID patient><COVID positive patient><COVID-19><COVID-19 infected patient><COVID-19 patient><COVID-19 positive patient><COVID-19 virus><COVID19 patient><COVID19 positive patient><COVID19 virus><CV-19><Cardiolipins><Cell surface><Cellular biology><Clinical><CoV-2><CoV2><Collaborations><Coronavirus Infectious Disease 2019><Critical Illness><Critically Ill><DNA><DNA Nucleases><DNase><Deoxyribonucleases><Deoxyribonucleic Acid><Development><Disease><Disorder><Endothelial Cells><Environment><Ethics><Familial antiphospholipid syndrome><Fostering><Generations><Goals><Hospital Admission><Hospitalization><Hospitals><Hughes syndrome><Human><Human Subject Research><Hyperactivity><Hypercoagulability><IgG><IgM><Immunoglobulin G><Immunoglobulin M><Impairment><In Situ><In Vitro><Individual><Infection><Inflammation><Inflammatory><Injury><Institution><Instruction><Investigators><Laboratories><Leadership><Learning><Length of Stay><Lupus><MOF syndrome><Marrow Neutrophil><Marrow platelet><Measures><Mediating><Medical Research><Medicine><Mentors><Mentorship><Mice><Mice Mammals><Michigan><Modern Man><Multiple Organ Dysfunction Syndrome><Multiple Organ Failure><Murine><Mus><Musculoskeletal Pain Disorder><Neurofibrillary Tangles><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Number of Days in Hospital><Organ><Pathogenesis><Pathogenicity><Patient Recruitments><Patients><Physicians><Platelets><Play><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Production><Property><Proteins><Regulatory Affairs><Research><Research Personnel><Researchers><Rheumatic Diseases><Rheumatism><Rheumatologic Diseases><Rheumatologic Disorder><Rheumatology><Risk><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infected patient><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Scientist><Self Tolerance><Sepsis><Serum><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Severity of illness><Statistical Methods><Thrombase><Thrombin><Thrombocytes><Thrombophilia><Thrombosis><Time><Training><Universities><Veins><Work><Writing><Wuhan coronavirus><animal experimentations><autoimmune antibody><autoimmune condition><autoimmune disorder><autoimmunity disease><autoreactive antibody><blood infection><bloodstream infection><career><career development><cell biology><clinical phenotype><cohort><coronavirus disease 2019><coronavirus disease 2019 infected patient><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 virus><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19><coronavirus disease-19 patient><coronavirus disease-19 virus><coronavirus infectious disease-19><coronavirus patient><developmental><disease severity><ethical><experiment><experimental research><experimental study><experiments><extracellular><fibrinogenase><hCoV19><hospital days><hospital length of stay><hospital stay><immunogen><improved><improved outcome><injuries><innovate><innovation><innovative><insight><large data sets><large datasets><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><microbicidal><microbicide><molecular phenotype><mortality><mouse model><multiorgan failure><multiple organ system failure><murine model><nCoV2><neurofibrillary degeneration><neurofibrillary lesion><neurofibrillary pathology><neutrophil><oral communication><pandemic><pandemic disease><participant recruitment><pathogenic autoantibodies><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><prevent><preventing><professor><prospective><public health relevance><rheumatologist><self reactive antibody><sepsis patients><septic patients><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><skills><social role><statistic methods><synergism><tangle><therapeutic target><thromboinflammation><thromboinflammatory><thrombotic disease><thrombotic disorder><tool><translational investigator><translational researcher><translational scientist><vascular>