Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1392&sort=end_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=end_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=end_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1393&sort=end_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1391&sort=end_date" }, "data": [ { "type": "Grant", "id": "11913", "attributes": { "award_id": "5UM2HD111076-02", "title": "Baylor College of Medicine Site Consortium - Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) Operations and Collaborations Center (UM2 Clinical Trial Optional)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)" ], "program_reference_codes": [], "program_officials": [], "start_date": "2022-09-22", "end_date": "2029-06-30", "award_amount": 312155, "principal_investigator": { "id": 26869, "first_name": "MARY E", "last_name": "PAUL", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 849, "ror": "", "name": "WESTAT, INC.", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Baylor College of Medicine Harris County, which includes the City of Houston, is among the 48 counties in the United States (U.S.) in which more than 50 percent of new HIV diagnoses occur. There is an urgent need for innovative and collaborative new approaches to HIV treatment and prevention in adolescents and young adults (AYA) in Houston. The long-term goal of this research is to move the U.S. and Houston area closer to ending the HIV epidemic by addressing the issues involved in successful prevention and treatment of HIV in AYA. These goals align with Adolescent Trials Network (ATN) research objectives and Houston Consortium partnerships will allow research to be conducted in AYA in all five priority areas of the ATN: improving HIV testing, preventing new infections, engaging youth in care, improving treatment and treatment effectiveness, and reducing adverse HIV health outcomes due to COVID-19. We plan to accomplish the following specific aims as a site for HIV care, research, and prevention in AYA. Aim 1 – Conduct the Trials of the ATN as identified by the ATN Executive Committee (EC) and Scientific Leadership Committee (SLC): Baylor College of Medicine (BCM) ATN site has a longstanding research unit with staff with years of experience working with AYA, both in a clinical trials settings and in the community, who are living with HIV (LWH) or are at risk for HIV. Aim 2 – Participate in the Development of Trials: BCM's ATN Project Lead and staff have years of experience in development and conducting of clinical trials in AYA and so will work in collaboration with the ATN Operations and Collaborations Center (OCC) to develop and conduct the trials performed in the ATN. In addition, the BCM Youth Community Advisory Board, (YCAB), which has had members who have been active in the ATN Youth Advisory Council (YAC) and National CAB, Youth Experts and Advocates for Health (ATN-YEAH), will evaluate and provide input on developing studies and provide and enhance ideas for future studies. Aim 3 – Provide Innovation Regarding Successful Recruitment and Enrollment of Participants: As an ATN Site Consortium, we have the structure, experience, and outreach to approach this aim at multiple levels with outreach in hard-to- reach AYA including racial and gender minority and homeless youth. Aim 4 – Provide Sites (Texas Children's Hospital and Harris Health Northwest and Thomas Street Health Center) as well as outreach within the Houston ATN Consortium, local laboratory capacity, and pharmacy support in order to conduct the ATN trials in collaboration with the OCC. Aim 5 – Continued evaluation and adjustment of Houston collaborative consortium leadership model for meaningful and continued community engagement as reflected in ATN research study participation of AYA at risk for or LWH. We anticipate the expected outcomes of improvements in each ATN priority area along the continuums of HIV infection and prevention. This project is high impact because it will provide the necessary consortium in impacted communities of AYA in a high-priority region of the U.S. to collaborate with the OCC to make sustainable progress in reaching the ATN goals.", "keywords": [ "AIDS prevention", "Acquired Immunodeficiency Syndrome", "Address", "Adherence", "Adolescent Medicine Trials Network", "Adolescent and Young Adult", "Advisory Committees", "Advocate", "Affect", "African American population", "Area", "Black race", "COVID-19", "COVID-19 pandemic", "Caring", "Cities", "Clinical Trials", "Collaborations", "Communities", "Conduct Clinical Trials", "County", "Development", "Discipline of Nursing", "Drug Kinetics", "Epidemic", "Evaluation", "Failure", "Feedback", "Future", "Goals", "HIV", "HIV Infections", "HIV diagnosis", "HIV/AIDS", "Health", "Healthcare", "Heterosexuals", "Hispanic", "Homeless Youth", "Human Resources", "Human immunodeficiency virus test", "Individual", "Infection", "Intervention", "Laboratories", "Latino", "Latinx", "Lead", "Leadership", "Low income", "Medicaid", "Medical", "Medicine", "Minority Groups", "Modality", "Modeling", "Newly Diagnosed", "Online Systems", "Outcome", "Pediatric Hospitals", "Pharmacy facility", "Prevention", "Reporting", "Research", "Risk", "Services", "Site", "Structure", "Technology", "Texas", "Treatment Effectiveness", "Uninsured", "United States", "Work", "Youth", "age group", "case-based", "college", "community engagement", "design", "ethnic minority population", "experience", "gender minority youth", "health inequalities", "high risk", "human old age (65+)", "improved", "improved outcome", "innovation", "male", "marginalized community", "meetings", "member", "motivational enhancement therapy", "novel strategies", "operation", "outreach", "participant enrollment", "pre-exposure prophylaxis", "prevent", "prevention service", "programs", "racial minority", "recruit", "research study", "sexual minority group", "testing services", "transmission process", "treatment services", "uptake" ], "approved": true } }, { "type": "Grant", "id": "10249", "attributes": { "award_id": "1R35HL161169-01", "title": "Cell competition in pulmonary fibrosis and ARDS", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 23738, "first_name": "Sara", "last_name": "Lin", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-08-20", "end_date": "2029-07-31", "award_amount": 954000, "principal_investigator": { "id": 26196, "first_name": "Stijn Piet Johan", "last_name": "De Langhe", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1426, "ror": "", "name": "MAYO CLINIC ROCHESTER", "address": "", "city": "", "state": "MN", "zip": "", "country": "United States", "approved": true }, "abstract": "Idiopathic pulmonary fibrosis (IPF) is a common form of interstitial lung disease (ILD), resulting in alveolar remodeling and progressive loss of pulmonary function, respiratory failure, and death often within 5 years of diagnosis. Genetic and experimental evidence support the concept that chronic alveolar epithelial injury and failure to properly repair the respiratory epithelium are intrinsic to IPF disease pathogenesis. Histologically, respiratory epithelial cells in the lung parenchyma are replaced by cells which are normally restricted to conducting airways. Fibrotic lesions and honeycomb structures replace alveoli, the latter normally lined by alveolar type 1 (AT1) and AT2 cells. Acute exacerbations by respiratory viral infections are the most devastating complication of IPF, having an in-hospital mortality rate of greater than 50%. Data from previous coronavirus pandemics such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), as well as emerging data from the COVID-19 pandemic, suggest there could be substantial fibrotic consequences following SARS-CoV-2 infection, the causative agent of COVID-19. Interestingly, the major risk factors for severe COVID-19 are shared with idiopathic pulmonary fibrosis (IPF), namely increasing age, male sex, and comorbidities such as hypertension and diabetes. Although many patients who develop acute respiratory distress syndrome (ARDS) survive the acute phase of the illness, a substantial proportion die as a result of progressive pulmonary fibrosis. It remains unclear why certain individuals are able to recover from ARDS, whereas in others there is a shift to unchecked cellular proliferation with the accumulation of BC-pods, fibroblasts and myofibroblasts. In these patients, there is also excessive deposition of collagen alongside other components of the extracellular matrix resulting in progressive pulmonary fibrosis. Distinct epithelial stem/progenitor cell pools and/or their mesenchymal niches repopulate injured tissue depending on the extent and type of injury, and the outcomes of regeneration or fibrosis in response to severe alveolar epithelial injury is dependent in part on the dynamics of cell competition between these cell populations. In tissues harboring a mosaic imbalance in cMyc or Yap protein levels, cells with higher cMyc or nuclear Yap levels become super- competitors and expand at the expense of cells with lower levels, by eliminating them. Alternatively, if certain stem cell populations are selectively wiped out due to the type of injury, other stem cell populations that escape the injury and which may not be so adept at replacing the destroyed tissue will now have a competitive advantage. For example, SARS-CoV-2 enters respiratory epithelial cells via its receptor, angiotensin-converting enzyme 2 (ACE2), causing severe airway and alveolar epithelial injury. Based on Ace2 expression, distinct stem/progenitor cell pools appear to be differentially susceptible to SARS-CoV-2 infection. This grant proposal seeks to manipulate the underlying mechanisms of cell competition to help prevent and treat IPF and ARDS. Cell competition might also be exploited to maximize the potential of healthy tissue replacement.", "keywords": [ "2019-nCoV", "ACE2", "AGTR2 gene", "Acute", "Acute Respiratory Distress Syndrome", "Age", "Alveolar", "Alveolus", "Applications Grants", "COVID-19", "COVID-19 pandemic", "Cell Proliferation", "Cells", "Cessation of life", "Chronic", "Collagen", "Complication", "Data", "Deposition", "Diabetes Mellitus", "Diagnosis", "Disease", "Epithelial", "Epithelial Cells", "Extracellular Matrix", "Failure", "Fibroblasts", "Fibrosis", "Genetic", "Histologic", "Hospital Mortality", "Hypertension", "Individual", "Injury", "Interstitial Lung Diseases", "Lesion", "Mesenchymal", "Middle East Respiratory Syndrome", "Mosaicism", "Myofibroblast", "Natural regeneration", "Nuclear", "Outcome", "Pathogenesis", "Patients", "Phase", "Population", "Proteins", "Pulmonary Fibrosis", "Respiratory Failure", "Risk Factors", "SARS-CoV-2 infection", "Severe Acute Respiratory Syndrome", "Structure", "Structure of parenchyma of lung", "Tissues", "Viral Respiratory Tract Infection", "airway epithelium", "alveolar epithelium", "base", "c-myc Genes", "comorbidity", "epithelial injury", "idiopathic pulmonary fibrosis", "injured", "male", "pandemic coronavirus", "prevent", "pulmonary function", "receptor", "repaired", "replacement tissue", "response", "severe COVID-19", "sex", "stem", "stem cell population", "stem cells" ], "approved": true } }, { "type": "Grant", "id": "10282", "attributes": { "award_id": "1R35HL161196-01", "title": "Investigating Individual Susceptibility and Host Response in Acute Respiratory Distress Syndrome", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 6344, "first_name": "Lora A.", "last_name": "Reineck", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-08-19", "end_date": "2029-07-31", "award_amount": 975000, "principal_investigator": { "id": 26236, "first_name": "Nuala Jennings", "last_name": "Meyer", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 232, "ror": "https://ror.org/00b30xv10", "name": "University of Pennsylvania", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "This R35 proposal is to support a robust translational research program focused on sepsis-associated acute respiratory distress syndrome (ARDS), explaining individual risk and characterizing the ARDS host immune response in order to identify molecular traits that may respond differently to specific therapy. The year 2020 and the SARS-CoV-2 pandemic placed a global spotlight on sepsis-associated ARDS and its lack of pharmacologic treatments, with over 400,000 American deaths. Even in non-pandemic years, however, ARDS complicates approximately 10% of all intensive care unit admissions and impacts close to 200,000 Americans. Mortality for ARDS has stubbornly exceeded 30%. I have used my translational science training to extend our knowledge of individual factors and pathways that influence ARDS risk and resolution, use genomic tools to infer which ARDS-associated plasma markers may be causal contributors to ARDS risk and mortality, and deeply characterize the host response to COVID-19 ARDS. I have grown a research program that includes a carefully phenotyped cohort of over 3,500 human subjects critically ill with sepsis, and curated biosamples at multiple timepoints to facilitate genomic and molecular discoveries, while contributing to the career development of multiple NHLBI-funded patient-oriented researchers. With the support of the R35, the Meyer research program will focus on 5 complementary themes to improve the health of patients with and at risk for sepsis-associated ARDS. Thematic area 1 concentrates upon understanding individual risk for ARDS and ARDS mortality, which will utilize whole genome association, expression and protein quantitative trait locus analysis, and genetic causal inference frameworks to evaluate inherited risks and identify which RNA and plasma traits may be causal intermediates in ARDS. Area 2 addresses the host response to ARDS, using deep immune profiling and integrated analyses to characterize and contrast the response to bacterial and viral sepsis-associated ARDS. In later years, sterile ARDS will be compared to infectious ARDS, and the contribution of activated T cells will be examined. Area 3 examines the interplay between ARDS and non-lung organ injuries during sepsis, particularly acute kidney injury, delirium and cognitive injury, and shock and circulatory dysfunction. We will identify DNA, RNA, plasma, and cytometric features specific to individual organ failures and shared across multiple organ systems. The R35 program will also catalyze two new areas of investigation for the Meyer lab. First, we will apply biomedical informatics techniques to integrate, visualize, and analyze multiple data networks – clinical, genomic, transcriptomic, proteomic, metabolomic, and cytometric – to identify coordinated patterns of response and their association with ARDS outcome. We will also examine the longitudinal host response to ARDS during recovery, testing for responses that predict or protect from post- intensive care syndrome. An investment in our research program will advance the prevention and personalized treatment of ARDS while fostering training and mentorship in lung health research.", "keywords": [ "Acute Renal Failure with Renal Papillary Necrosis", "Acute Respiratory Distress Syndrome", "Address", "Admission activity", "American", "Area", "Bacteremia", "COVID-19 pandemic", "COVID-19/ARDS", "Cessation of life", "Clinical", "Cognitive", "Cohort Studies", "Critical Illness", "DNA", "Data", "Delirium", "Fostering", "Functional disorder", "Funding", "Genetic", "Genomics", "Goals", "Health", "Human", "Immune", "Immune response", "Individual", "Inherited", "Injury", "Intensive Care", "Intensive Care Units", "Investigation", "Investments", "Knowledge", "Medicine", "Mentorship", "Molecular", "National Heart Lung and Blood Institute", "Organ failure", "Outcome", "Pathway interactions", "Patients", "Pattern", "Pharmacological Treatment", "Phenotype", "Plasma", "Predisposition", "Prevention", "Proteins", "Proteomics", "Quantitative Trait Loci", "RNA", "Recovery", "Research", "Research Personnel", "Resolution", "Risk", "Sepsis", "Shock", "Sterility", "Syndrome", "T-Lymphocyte", "Techniques", "Testing", "Time", "Training", "Translational Research", "Viremia", "biomedical informatics", "body system", "career development", "cohort", "genomic tools", "human subject", "improved", "individualized medicine", "lung health", "metabolomics", "mortality", "organ injury", "patient oriented", "personalized medicine", "predicting response", "programs", "response", "sepsis induced ARDS", "trait", "transcriptomics", "translational research program", "whole genome" ], "approved": true } }, { "type": "Grant", "id": "15191", "attributes": { "award_id": "1R01DC021422-01A1", "title": "Towards a molecular biology of human olfaction in health and disease", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Deafness and Other Communication Disorders (NIDCD)" ], "program_reference_codes": [], "program_officials": [ { "id": 6520, "first_name": "SUSAN L.", "last_name": "SULLIVAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-01", "end_date": "2029-07-31", "award_amount": 682219, "principal_investigator": { "id": 21603, "first_name": "Sandeep R", "last_name": "Datta", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 855, "ror": "", "name": "HARVARD MEDICAL SCHOOL", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 31772, "first_name": "Bradley J", "last_name": "Goldstein", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 246, "ror": "https://ror.org/00py81415", "name": "Duke University", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "The olfactory epithelium is the peripheral organ for smell, housing millions of primary olfactory sensory neurons. Insults such as inflammation, infection, toxins or trauma can damage the olfactory epithelium and perturb olfactory function, causing lasting anosmia, hyposmia or parosmia. We lack both a basic understanding of what goes wrong when people lose their sense of smell, and effective therapies for sensorineural olfactory disorders, as highlighted by our current inability to treat post-COVID olfactory dysfunction impacting millions of people. Thus, there is an urgent unmet need to define mechanisms driving olfactory neuronal homeostasis and dysfunction in humans. In rodents, each olfactory neuron harbors a unique transcriptome based upon the singular olfactory receptor it expresses, organized into coherent gene expression programs. Fixed gene expression programs specify each neuron’s identity, and flexible programs are dynamically adjusted based upon odor exposure. These findings have enabled genome-wide characterization of odor responses in vivo in mice, across the entire olfactory neuron population. However, humans express far fewer olfactory receptors than mice, and neither their specific receptive odor repertoire nor their dynamic in vivo transcriptional variation have been well-defined. Unlike in rodents, we know little about how gene expression is organized in human olfactory neurons, how populations of human olfactory neurons respond to defined odors, or how odor-evoked olfactory neuron activity is altered in the setting of disease. The experiments proposed here will identify organized patterns of gene expression in olfactory neurons isolated from human biopsies, in both controls and in subjects with objective smell loss, via two specific aims: Specific Aim 1 will establish the axes of transcriptional variation in human OSNs; Specific Aim 2 will assess responses to odor at the single cell level in the human olfactory epithelium. Olfactory mucosal biopsies from normosmic or hyposmic subjects will be analyzed using single cell RNA-sequencing. Presenting a specific odorant to subjects prior to biopsy and sequencing, an approach termed Act-seq will be employed to query the responses of the entire olfactory neuron array to a given odor in vivo. Act-seq will be compared from normosmic or post-Covid hyposmic olfactory samples. Completion of the proposed work will (1) directly define human odor-induced alterations in olfactory cells in normal or diseased conditions, (2) provide the first in vivo human olfactory receptor de- orphanization, and (3) produce novel datasets that will be broadly useful to the neurobiology and chemosensory research communities. These results, defining mechanisms driving olfactory neuronal homeostasis and dysfunction in humans, will form a basis for future clinical research trials aimed at promoting recovery of olfaction.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15227", "attributes": { "award_id": "1R01AI180050-01A1", "title": "Development of anti-LPS therapeutic antibodies for the treatment of Pseudomonas aeruginosa infections", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 23961, "first_name": "Zuoyu", "last_name": "Xu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-08-01", "end_date": "2029-07-31", "award_amount": 741917, "principal_investigator": { "id": 31809, "first_name": "Mariette", "last_name": "Barbier", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1093, "ror": "https://ror.org/011vxgd24", "name": "West Virginia University", "address": "", "city": "", "state": "WV", "zip": "", "country": "United States", "approved": true }, "abstract": "The goal of this proposal is to develop therapeutic antibodies for the treatment of multidrug resistant (MDR) P. aeruginosa infections, with an emphasis on sepsis. With the rise in antimicrobial resistance around the world we are running out of therapeutic options against MDR P. aeruginosa. Our laboratory has identified a potential solution to address this problem: a therapeutic antibody cocktail that targets the lipopolysaccharide of P. aeruginosa. One of the antibodies present in the cocktail (WVU-VDC-S3D4, or S3D4 for short) completely protects mice against lethal sepsis, preventing bacterial dissemination and cytokine storm. This antibody is also more potent than vaccination with a P. aeruginosa whole cell vaccine or passive immunization with serum from whole cell vaccinated mice. Most interestingly, S3D4 is also capable of directly killing P. aeruginosa in vitro in the absence of complement or immune cells. In this proposal, we will characterize the mechanism of action of S3D4, formulate it in an LPS multivalent antibody cocktail, and evaluate efficacy against MDR P. aeruginosa. To do this, we will evaluate host and bacterial factors involved in S3D4 function (Aims 1 and 2). We will then combine it as cocktail with three additional antibodies that target the 6 LPS serogroups that cause 87% of P. aeruginosa bloodstream infection. Efficacy in vitro and in vivo will be evaluated with MDR clinical isolates (Aim 3). We will also evaluate efficacy against P. aeruginosa biofilms. We hypothesize that a multivalent anti-LPS cocktail of antibodies, alone or in combination with standard of care antibiotics, will be efficacious for the prevention and treatment of MDR P. aeruginosa sepsis. By the completion of these studies, we anticipate to elucidate the mechanism of action of a novel class of antibodies that can directly kill P. aeruginosa in vitro, which will help with the production of additional antibodies with similar functions against other MDR organisms. We will also produce proof of concept data to support the generation antibody therapy against P. aeruginosa infections. Altogether, this project will generate important knowledge to improve the lives of patients affected by this MDR bacterium.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15231", "attributes": { "award_id": "1K08AI180347-01", "title": "Elucidating the impact of immune imprinting on SARS-CoV-2 variant vaccination strategies using a humanized mouse model", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 26918, "first_name": "Michelle Marie", "last_name": "Arnold", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-08-15", "end_date": "2029-07-31", "award_amount": 193644, "principal_investigator": { "id": 31815, "first_name": "Anthony", "last_name": "Bowen", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 781, "ror": "", "name": "COLUMBIA UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT: Rationale: Continued evolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to immune-evasive variants that pose a persistent threat to global public health. Updated vaccines are needed to provide improved immune responses against emerging variants, but current approaches targeting the Omicron BA.4/5 variant may have limited effectiveness due to immune imprinting caused by prior immune system exposure to ancestral D614G variant antigens. Our preliminary data suggests that bivalent boosters targeting BA.4/5 do not provide superior neutralizing antibody (NAb) responses to SARS-CoV-2 variants compared to the original monovalent vaccine. This mentored career project aims to elucidate the impact and molecular basis of immune imprinting following primary D614G vaccination on subsequent humoral responses to variant antigens. Candidate: As an Infectious Diseases physician with a PhD in Microbiology and Immunology, I am uniquely positioned to bridge the gap between biomedical research and patient care to advance our knowledge of humoral immune responses to SARS-CoV-2. Further training in virology, structural biology, bioinformatics, and monoclonal antibody characterization will be crucial for completion of the proposed research and my development as an independent physician-scientist specializing in humoral immunity to pathogens of global importance. I have a globally recognized mentor in Dr. David Ho and benefit from an outstanding multidisciplinary team of experts to guide my training and research progress. Environment: The Ho laboratory at the Columbia University Irving Medical Center (CUIMC) is a leading group in the study of SARS-CoV-2, with expertise in the characterization of viral variants and monoclonal antibodies. This enriching environment provides access to a large network of collaborators including experts in cryo-electron microscopy, single cell sequencing, and antibody repertoire analysis. CUIMC also has a strong track record of enabling junior physician-scientists to develop independent and successful careers in academic medicine. Approach: Our central hypothesis is that primary vaccination targeting the SARS-CoV-2 D614G strain induces immunological imprinting that restricts antibody responses to subsequently encountered viral variant antigens. In Aim 1, we will test the impact of imprinting on NAb responses following BA.4/5 boosting strategies in a humanized mouse model. In Aim 2, we will characterize the antibody repertoires of immunized mice to identify imprinting effects using single B cell sequencing and bioinformatic approaches. In Aim 3, we will use high- throughput techniques to produce monoclonal antibodies, determine their neutralizing activity, and identify epitopes associated with imprinting responses though structural and binding assays. Through these aims, we will expand understanding of the immunologic and structural basis underlying imprinting in SARS-CoV-2. Our results should inform novel strategies for structure-based vaccine design to circumvent imprinting responses and produce broader immunity to SARS-CoV-2 variants and possibly other antigenically variable pathogens.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15232", "attributes": { "award_id": "1K01HL174822-01", "title": "Endothelial S1PR1 promotes lung repair in post-viral ARDS", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 20693, "first_name": "Roya", "last_name": "Kalantari", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-08-01", "end_date": "2029-07-31", "award_amount": 161240, "principal_investigator": { "id": 31816, "first_name": "Patricia Louise", "last_name": "Brazee", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 736, "ror": "https://ror.org/002pd6e78", "name": "Massachusetts General Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Viral respiratory infections, such as influenza and SARS-CoV2, frequently lead to acute respiratory distress syndrome (ARDS), a condition with a mortality up to 46%. Endothelial injury, dysfunction and the resultant vascular hyperpermeability contribute to the severity of ARDS, persistence of lung injury, and dysregulated repair with the development of fibrosis. While sphingosine-1-phosphate receptor 1 (S1PR1) is a key protective signaling axis on endothelial cells, the role of S1PR1 signaling in the resolution of lung injury in post-viral ARDS has not been well explored. The objective of this application is to define endothelial S1PR1-dependant pathways which promote the re-alveolarization of the post-viral lung needed to prevent morbid fibrotic outcomes. We hypothesize that endothelial S1PR1 signaling promotes productive lung repair after viral infection via BMP2 mediated support of the epithelial niche. These preliminary findings a new facet to the pleotropic benefits of EC S1PR1 beyond its established role in limiting vascular hyperpermeability and highlight a need to comprehensively validate the therapeutic potential of augmenting S1PR1 expression to limit post-viral pulmonary fibrosis. We will test this hypothesis via two specific aims: 1) determine the mechanism of endothelial S1PR1 mediated epithelial repair after viral-induced ARDS, and 2) determine how EC S1PR1 regulation can be therapeutically augmented to attenuate post-viral fibrosis. The proposed research will reveal novel links between EC S1PR1 and epithelial regeneration and differentiation after viral infection and identify regulators of endothelial function which can be therapeutically targeted to attenuate post- viral fibrosis. Dr. Brazee’s long-term goal is to be an independent basic and translational investigator with a research program aimed at understanding the contributions of the endothelium in supporting productive lung repair pathways. The proposed K01 research aims utilize prior training in mouse models of influenza virus infection, fibrotic lung disease, and fundamental molecular biology techniques. In addition, the project will necessitate advanced training in vascular and epithelial biology, G-protein coupled receptor (GPCR) signaling, and translational modeling of human disease using human derived 3D organoids and precision cut lung slices. Successful completion of these aims, together with continued professional development, will provide the proficiencies necessary to establish a productive research program and an impactful career as an independent R01-funded investigator.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15236", "attributes": { "award_id": "1K08AI178093-01A1", "title": "SARS-CoV-2 immune responses in patients with lymphoma", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 6125, "first_name": "Timothy A.", "last_name": "Gondre-Lewis", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-08-23", "end_date": "2029-07-31", "award_amount": 192888, "principal_investigator": { "id": 31821, "first_name": "Andres", "last_name": "Chang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 265, "ror": "https://ror.org/03czfpz43", "name": "Emory University", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true }, "abstract": "Non-Hodgkin lymphoma and chronic lymphocytic leukemia (NHL/CLL) patients have immune system deficits that arise from the cancer and are aggravated by lymphoma therapies, placing them at higher risk of morbidity and mortality after infection with viruses like influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients are strongly recommended to get vaccinated and boosted with SARS-CoV-2 mRNA vaccines, but antibody responses after vaccination in these patients are often impaired. SARS-CoV-2 vaccines also elicit T cell responses in healthy individuals that may be protective but previous studies indicate that T cells from NHL/CLL patients are also dysfunctional. Under the mentorship of Drs. Rafi Ahmed and Jonathon Cohen, I have assembled a cohort of over 600 NHL/CLL patients with over 1,300 longitudinal blood samples paired with clinical data that I have used to study the immune responses in this patient population. Using this cohort, I showed that most patients have lower antibody responses after SARS-CoV-2 vaccination than otherwise healthy individuals and that antibody responses correlate at least partly with lymphoma therapies. I have also shown that some patients produce spike-specific CD4+ and CD8+ T cells after vaccination. The longitudinal, antigen-specific CD4+ and CD8+ T cell responses after vaccination and infection have not been well characterized in NHL/CLL patients. I hypothesize that these patients have alterations in their CD4+ and CD8+ T cell responses after antigen stimulation, which are dependent on the underlying lymphoma subtype and lymphoma therapy. This proposal has 3 goals: 1) To evaluate the generation, differentiation, breadth, and persistence of SARS- CoV-2-specific CD4+ T cell responses in NHL/CLL patients after vaccination and infection using functional assays and single cell sequencing technologies; 2) To define the primary and memory SARS-CoV-2-specific CD8+ T cell responses after vaccination and infection through functional assays and single cell sequencing technologies; and 3) to support my transition from a trainee in Dr. Ahmed’s laboratory to leading an independent research program. Successful completion of these studies will provide in-depth knowledge of the generation, evolution, breadth, and persistence of antigen-specific T cell responses in NHL/CLL patients after vaccination and infection. This knowledge will facilitate the design of interventions that may improve vaccine responses in these and other immunosuppressed patients, protecting them from potentially life-threatening viral infections like SARS-CoV-2 and influenza. Moreover, the insights on the generation and maintenance of adaptive immune responses against novel antigens obtained from these studies could help fuel the development of better cancer immunotherapies.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15238", "attributes": { "award_id": "1U01IP001265-01", "title": "IP24-045, SEAPREP: Seattle Pandemic Preparedness Cohort", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Center for Immunization and Respiratory Diseases (NCIRD)" ], "program_reference_codes": [], "program_officials": [], "start_date": "2024-08-01", "end_date": "2029-07-31", "award_amount": 3874443, "principal_investigator": { "id": 11527, "first_name": "Helen Ying-hui", "last_name": "Chu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Community-based surveillance studies of respiratory viruses provide the opportunity for early viral detection and situational awareness, and may inform early public health efforts to mitigate the transmission of respiratory viruses, as was evidenced by the SARS-CoV-2 pandemic. Case-ascertained household transmission studies are an efficient and epidemiologically rich method to study respiratory virus transmission. Our team of investigators has deep expertise in community surveillance and case-ascertainment trials of respiratory viruses. Our group of collaborators include specialists in infectious diseases, epidemiology, biostatistics, virology, immunology, and infectious disease modeling. In 2018, we developed the infrastructure for a pandemic preparedness platform in Seattle, Washington, leading to the first identification of SARS-CoV-2 community transmission in the United States. We have developed innovative methods for fully remote observational studies of respiratory viruses in households, and have built a logistics and laboratory insfrastructure for rapid delivery and pickup of biospecimens, multiplex testing for a panel of respiratory pathogens, in-depth immunologic characterization, and whole genome sequencing and visualization. In this study, we propose to build on these platforms to conduct the following studies. First, we propose a prospective longitudinal cohort study of 2000 children and adults in the Seattle area, with weekly symptom screening and collection of nasal swabs for respiratory illness. We will conduct multi-pathogen testing for respiratory viruses and whole genome sequencing for RSV, SARS-CoV-2, and other respiratory viruses. We will calculate incidence, assess epidemiology and burden of respiratory viruses, measure participant knowledge, attitudes and perceptions, and measure the effectiveness of interventions in prevention of disease. We additionally propose to perform in-depth immunologic assessments by collection of serum samples longitudinally in a subset of individuals to understand antibody kinetics over the course of multiple seasons, and the effects of vaccines and infections on antibody titers across age groups. For our second study, we propose to conduct a case-ascertained household transmission study to understand transmission dynamics of SARS-CoV-2, RSV, and other viruses. Index cases will be enrolled remotely along with their household members, for serial self-swab collection for a period of two weeks after enrollment. We propose collection of environmental samples within a subset of households. Molecular testing and sequencing will be performed for SARS-CoV-2, RSV, and other viruses, as indicated, allowing for calculation of household attack rates, serial intervals, and risk factors for within household transmission for known and novel pathogens. These proposed studies will provide real-time situational awareness of community respiratory epidemiology, and our team has the experience and expertise to pivot for identification of novel pathogens and pandemic response.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15240", "attributes": { "award_id": "1K23HL168161-01A1", "title": "K23 Resubmission - Impact of adoptive T cell therapy on immunity to SARS-CoV-2 after bone marrow transplant", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 24472, "first_name": "LISBETH A", "last_name": "WELNIAK", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-08-15", "end_date": "2029-07-31", "award_amount": 160518, "principal_investigator": { "id": 31825, "first_name": "Susan", "last_name": "Conway", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1167, "ror": "", "name": "CHILDREN'S RESEARCH INSTITUTE", "address": "", "city": "", "state": "DC", "zip": "", "country": "United States", "approved": true }, "abstract": "The overarching goal of this proposal is the development of the candidate into an independent investigator in the field of immune modulatory cell therapy for critically ill children, particularly those post hematopoietic stem cell transplant (HSCT). With her clinical and research background in pediatric critical care and T cell immunotherapy, she is ideally positioned to fully realize the benefits of an NIH Mentored Career Development Award. This research proposal seeks to establish the safety and preliminary efficacy of adoptive immunotherapy with donor-derived SARS-CoV-2-specific T cells (CST) for prophylaxis against SARS-CoV-2 infection in patients post HSCT by conducting an FDA- and IRB-approved phase I clinical trial (NCT 05141058) and to develop CSTs genetically engineered to maintain antiviral activity in the presence of the commonly used lymphodepleting agent, alemtuzumab. The specific aims of the proposal are: 1) to determine whether infusion of donor-derived CSTs safely enhances antiviral immunity to SARS-CoV-2 in patients early (<4 months) post HSCT, and 2) to genetically engineer CSTs to retain antiviral activity in vitro in the presence of alemtuzumab. Together, these aims will establish the safety and preliminary efficacy of CST prophylaxis in the post HSCT population and lay the foundation for a “next generation” of virus-specific T cells (VST) engineered to resist immunosuppressive peri- transplant drugs. In addition, they will develop the candidate's expertise in T cell immunobiology, high throughput sequencing, gene editing, and early phase clinical trials. The candidate has assembled an outstanding advisory team who are highly qualified to guide her in the pursuit of her career and research goals. Her primary mentor and co-mentor, Drs. Catherine Bollard and Michael Keller, are world-renowned experts in immune modulatory cellular therapy and T cell immunobiology. Dr. Matthew Porteus, a pioneer in the field of gene therapy, will guide her work developing genetically engineered CSTs. In addition, Dr. Patrick Hanley, Director of the Good Manufacturing Processes Laboratory at Children's National Hospital, will oversee production of the CST product (IND 27588); Dr. Rick Jones will advise and oversee trial conduct at Johns Hopkins Medical Institutions (JHMI); and Dr. Wei Li will provide bioinformatic support for both CRISPR and high throughput sequencing experiments. A selection of focused coursework and seminars will facilitate investigator independence by the end of the award period. The candidate will benefit from a superb academic environment and extensive resources available through the Center for Cancer and Immunology Research, the Genetic Medicine Research Center, and the Clinical and Translational Science Institute at Children's National, as well as from in-person training in gene editing in the Porteus laboratory. In summary, this proposal describes a plan that is relevant, feasible, and will provide the necessary mentorship and training to promote the candidate's development into an independent clinician scientist in the field of cellular immune modulatory therapy.", "keywords": [], "approved": true } } ], "meta": { "pagination": { "page": 1392, "pages": 1405, "count": 14046 } } }