Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=3&sort=other_investigators
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=other_investigators", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=other_investigators", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=4&sort=other_investigators", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=2&sort=other_investigators" }, "data": [ { "type": "Grant", "id": "15167", "attributes": { "award_id": "1K01HL165086-01A1", "title": "LeveRaging Community Engagement to SusTAIN NCD InTegrated Care Models (RETAIN-IT)", "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": 31750, "first_name": "Keith A", "last_name": "Mintzer", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-01", "end_date": "2029-08-31", "award_amount": 162820, "principal_investigator": { "id": 31751, "first_name": "Angela", "last_name": "Aifah", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 832, "ror": "", "name": "NEW YORK UNIVERSITY SCHOOL OF MEDICINE", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "The increased life expectancy of people living with HIV/AIDS (PLWH) and the associated burden of non- communicable diseases (NCDs) in PLWH has prompted an urgent need for effective community engaged strategies that engage care PLWH with comorbid NCDs in clinical treatment. Current integrated models of care lack a focus on community engagement as a strategy to refer impacted individuals to clinical treatment – an integral aspect of translating evidence-based practices (EBPs) in LMICs. More specifically, despite the use of community clinical linkages as an effective strategy to link impacted individuals to clinical treatment for complex health conditions (such as opioid use disorder and emerging infections like the COVID-19 pandemic), its use for NCD prevention among PLWH and comorbid hypertension in low- and middle-income countries (LMICs) is suboptimal. In order to sustain the public health gains made in the treatment of HIV, community clinical linkages must be prioritized as a key component of HIV/NCD integrated care models in LMICs. Guided by the Community- Based System Dynamics (CBSD) and Human-Centered Design (participatory approaches that involve participants in developing solutions to complex system challenges), this K01, “LeveRaging Community Engagement to SusTAIN NCD InTegrated Care Models (RETAIN-IT)”, leverages the infrastructure of a community-based organization (Network of People Living with HIV in Nigeria (NEPWHAN)) to co-develop a community-clinical linkage (CCL) model that will facilitate the referral of PLWH to primary healthcare centers for hypertension treatment. The research aims of this proposal are to: 1) identify and map the multi-level barriers and facilitators of developing a community-clinical linkage model for care of PLWH and comorbid hypertension in Akwa Ibom, Nigeria; 2) co-develop with NEPWHAN, a culturally tailored, community led strategy for linking PLWH with comorbid hypertension to primary health centers for management of hypertension; and 3) assess the acceptability, appropriateness, and feasibility of the community-led strategy using a pre-post pilot study design. To accomplish these research aims and prepare for a larger study, the applicant will receive training in: 1) systems science theory and methods, including community-based system dynamics; 2) partnership building with community partners; and 3) in using community clinical linkage models as an implementation strategy for advancing evidence-based practices for integrated models of care in PLWH and comorbid NCDs under the direction of Drs. Gbenga Ogedegbe, Antoinette Schoenthaler, Nadia Islam, Brita Roy, and Dike Ojji. Findings from the proposed research will advance research on the role of community clinical linkages in sustaining integrated NCD models of care in LMICs and directly aligns with NHLBI’s strategic goal to advance translational research by facilitating innovation and accelerating research translation.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15302", "attributes": { "award_id": "1F31AI183832-01", "title": "Immunometabolic regulation of enteric viral infection", "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": 26943, "first_name": "Diane S.", "last_name": "Adger-Johnson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-08-01", "end_date": "2026-07-31", "award_amount": 35482, "principal_investigator": { "id": 31893, "first_name": "Jasmine", "last_name": "Wright", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 827, "ror": "", "name": "WASHINGTON UNIVERSITY", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "Obesity is a global health concern as it is a risk factor for several of the leading causes of death such as heart disease, kidney disease, and type 2 diabetes. Obesity drives dysregulated inflammation, which has been shown to be a risk factor for increased morbidity and mortality in certain pulmonary viral infections such as influenza A and SARS-CoV-2. Yet it is unknown how diet induced obesity (DIO)-associated inflammation impacts the immune response to viruses that infect the gastrointestinal tract. It has been well-established that DIO drives dynamic changes in intestinal immunity, including alterations in interferon gamma and IgA production. Specifically, DIO induces skewing towards type I immunity, which is protective against intracellular pathogens like viruses. Norovirus (NV) is one of the most prevalent gut viruses, as it is the number one cause of acute viral gastroenteritis worldwide. However, the effects of DIO induced type 1, or anti-viral, skewing on immunity to NV have yet to be elucidated. My new preliminary data indicate that mice placed on a high fat diet (HFD) prior to infection with persistent murine NV (MNV) strain CR6 clear the infection in just 28 days, while mice fed normal chow (NC) remain persistently infected. This clearance appears to be independent of MNV receptor expression and viral tropism. Additionally, we found that obese patients with symptoms of gastroenteritis are less likely to test positive for NV than symptomatic lean controls, which further supports our mouse model indicating a HFD is protective against NV infection in both mice and humans. We also observe changes in the humoral response to MNV in our mouse model, as HFD-fed mice have an increase in serum MNV specific IgG and decrease in both serum and secretory MNV specific IgA in comparison to infected mice on NC. These findings lead to my central hypothesis that obesity drives alterations in intestinal immunity that promote an anti-viral state and protect against norovirus infection. I have proposed two aims to address this hypothesis. In Aim 1, I will elucidate the role of DIO-mediated changes in B and T cell responses in protection against MNV infection. In Aim 2, I will determine the role of interferon signaling in DIO-associated clearance of MNV. This novel work will advance our understanding of the relationship between diet and immunity to NV infection. This work also has translational potential as it may provide insight to treatment for NV, as there is currently no vaccine for this common virus.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15174", "attributes": { "award_id": "1R03HS030016-01A1", "title": "Assessing the Impact of Health System Ownership on Fulfilling the Vision of High-Quality Primary Care and Whole Health", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Agency for Healthcare Research and Quality (AHRQ)" ], "program_reference_codes": [], "program_officials": [ { "id": 27219, "first_name": "Aimee", "last_name": "Eden", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-01", "end_date": "2026-08-31", "award_amount": 49777, "principal_investigator": { "id": 31759, "first_name": "E. Marshall", "last_name": "Brooks", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 672, "ror": "https://ror.org/02nkdxk79", "name": "Virginia Commonwealth University", "address": "", "city": "", "state": "VA", "zip": "", "country": "United States", "approved": true }, "abstract": "TITLE: Assessing the Impact of Health System Ownership on Fulfilling the Vision of High-Quality Primary Care and Whole Health PROJECT SUMMARY The National Academies of Sciences, Engineering, and Medicine’s (NASEM) reports “Implementing High Quality Primary Care'' and “Achieving Whole Health: A New Approach for Veterans and the Nation'' call for coordinated systems level approaches to care.1,2 In response to these calls for action and stresses on primary care from the COVID pandemic and other market forces, primary care practices are increasingly owned by health systems. In Virginia we have documented that between 2018 and 2022 there was an increase from 25% to 43% of practices being owned by a health system with a concurrent decline in clinician ownership.3 These changes could both help (e.g., provide a systems level approach, expanded interprofessional teams, new resources) and/or undermine (e.g., reduce local decision-making authority, replace ambulatory focus with hospital interests, undermine organizational culture) the ability to achieve NASEM’s vision. We propose an explanatory sequential mixed-methods study using multimedia elicitation surveys and focus group interviews to assess the impact of ownership on high-quality primary care and whole health care and to describe contextual factors that may impact care. Building on our ongoing, longitudinal assessment of primary care in Virginia conducted in the Ambulatory Care Outcomes Research Network (ACORN), we will randomly sample 30 primary care practices throughout the state, stratified by practices that in the past 5 years (a) moved from clinician to hospital ownership, (b) stayed clinician owned, or (c) stayed hospital owned. The survey will consist of a brief multimedia presentation, developed in collaboration with the NASEM report authors, of the key elements of high-quality primary care and whole health, immediately followed by Likert scale questions to assess team members’ attitudes, current practice, and confidence in the ability to improve on these elements. The survey will be digitally administered with REDCap software to representatives of each clinical team member type. To develop the multimedia elicitation survey, we will work with the NASEM report authors and committee members to distill and operationalize core elements articulated in the reports, including questions on equity, accessibility, integration, interprofessional teamwork, professional satisfaction and team wellbeing, and community engagement. A practice structural questionnaire will also collect information on practice organization and staffing levels, patient volume and population demographics, payer mix, EHR capabilities, enhanced access options, and participation in innovative payment models. Follow-up group interviews with practice teams will reflect on team survey responses and assess the organizational, practice, and individual level factors influencing high-quality primary care and whole health care. Study findings will be used to further AHRQ’s mission of revitalizing the Nation’s primary care system, promote the NASEM vision of Whole Health in primary care, and develop future interventions to help primary care deliver high-quality and whole health care in diverse ownership settings.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15079", "attributes": { "award_id": "5R37MH101495-11", "title": "Psychobiological Mechanisms Underlying the Association Between Early Life Stress and Depression Across Adolescence", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 23085, "first_name": "Eric Rousseau", "last_name": "Murphy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-05-01", "end_date": "2028-02-29", "award_amount": 655207, "principal_investigator": { "id": 27431, "first_name": "IAN H", "last_name": "GOTLIB", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 266, "ror": "https://ror.org/00f54p054", "name": "Stanford University", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "More than 50% of youth will experience at least one form of significant adversity in early life. Such adversities pose significant risk not only for the development of psychopathology over the life course, but also for attempted suicide, a leading cause of death in people ages 10-24 years. We have recruited and assessed 220 9- to 13-year-old boys and girls across four timepoints, each two years apart, to examine the effects of exposure to ELS on trajectories of stress reactivity and reward sensitivity, and, in turn, their impact on the onset of psychopathology and suicidal behaviors across adolescence. In this cohort we have conducted repeated measurements of symptoms and diagnoses of psychopathology, neural, endocrine, cognitive, immunological, and behavioral assessments of stress reactivity and reward sensitivity, and early exposure to adversity, including the type, severity, and timing of stressful events. We have published a series of papers from this project elucidating the effects of ELS on psychobiological functioning, trajectories of brain development, and biological aging, and the consequences of these alterations for clinical functioning. In this MERIT renewal application, we propose to build on and extend our work in three important ways. First, we will conduct an additional assessment of our participants at age 20 in order to examine the effects of ELS on trajectories of neurodevelopment and clinical outcomes from childhood to young adulthood, as well as the persistence of COVID-19 pandemic-related difficulties in mental health, stress, and brain metrics. We will also extend our examination of how environmental pollutants and conditions affect relations among these variables. Second, we will extend and replicate our findings in a younger, non-Western sample by analyzing data from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) project, an ongoing prospective study in which many of the same, or comparable, measures that we administered in our project have also been collected regularly from approximately 1,500 parents and children since the prenatal period. Extending and replicating our findings with the GUSTO dataset, which includes younger, non-Western children from Southeast Asian families in Singapore, will complement findings from other large cohorts, like ABCD and NCANDA, that have assessed only Western participants. Finally, will leverage our own and GUSTO data to examine the effects of the COVID-19 pandemic shutdown on children’s and adolescents’ psychobiological functioning. In both datasets we have a unique opportunity to compare comprehensive psychobiological data collected from the same youth before and after the pandemic shutdowns in order not only to examine how the pandemic has altered young people’s psychobiological functioning and development, but importantly, to also identify risk and resilience factors across cultural contexts. Further, the new proposed adult assessment in our ELS project will allow us to examine the persistence of COVID-related difficulties by re-assessing participants whom we studied soon after pandemic quarantine restrictions ended.", "keywords": [ "13 year old", "9 year old", "Address", "Adolescence", "Adolescent", "Adult", "Adverse effects", "Affect", "Age", "Air Pollutants", "Award", "Behavior assessment", "Behavioral", "Biological", "Biological Aging", "Blood", "Brain", "COVID-19", "COVID-19 impact", "COVID-19 pandemic", "COVID-19 pandemic effects", "Cause of Death", "Child", "Childhood", "Clinical", "Cognitive", "Cohort Studies", "Collaborations", "Complement", "Data", "Data Analytics", "Data Set", "Development", "Diagnosis", "Dimensions", "Disease", "Endocrine", "Environmental Exposure", "Environmental Pollutants", "Equation", "Exposure to", "Family", "Grant", "Health", "Immunologics", "Interview", "Life", "Life Cycle Stages", "Machine Learning", "Measurement", "Measures", "Mental Depression", "Mental Health", "Modeling", "Not Hispanic or Latino", "Outcome", "Paper", "Parents", "Participant", "Persons", "Physiology", "Predictive Factor", "Prevention", "Prevention program", "Prospective Studies", "Psychopathology", "Publishing", "Quarantine", "Rewards", "Risk", "Risk Factors", "Saliva", "Sampling", "Series", "Severities", "Singapore", "Specimen", "Stress", "Stressful Event", "Suicide attempt", "Symptoms", "Techniques", "Testing", "United States National Institutes of Health", "Work", "Youth", "boys", "cohort", "deprivation", "early life adversity", "early life stress", "economic disparity", "experience", "girls", "health disparity populations", "high risk", "large datasets", "longitudinal dataset", "neural", "neurodevelopment", "neuroimaging", "pandemic disease", "prenatal", "promote resilience", "psychobiologic", "psychosocial", "public health relevance", "racial population", "recruit", "resilience", "resilience factor", "risk prediction", "southeast Asian", "stress reactivity", "suicidal behavior", "treatment program", "young adult" ], "approved": true } }, { "type": "Grant", "id": "15245", "attributes": { "award_id": "4R00AA030628-03", "title": "Regulation of alcohol-induced social disturbances by lateral habenula serotonin receptors", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Alcohol Abuse and Alcoholism (NIAAA)" ], "program_reference_codes": [], "program_officials": [ { "id": 12239, "first_name": "Qi-Ying", "last_name": "Liu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-08-25", "end_date": "2027-07-31", "award_amount": 249000, "principal_investigator": { "id": 27208, "first_name": "Meghan Elizabeth", "last_name": "Flanigan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1179, "ror": "https://ror.org/012jban78", "name": "Medical University of South Carolina", "address": "", "city": "", "state": "SC", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic has greatly exacerbated rising patterns of excessive alcohol consumption, particularly in women. Binge alcohol drinking is the most common pattern of excessive alcohol drinking and is associated with increased risk of developing mood disorders and Alcohol Use Disorder (AUD). Social support strongly buffers against alcohol craving and relapse, yet many individuals display reduced valuation of social rewards and/or deficits in the processing of social stimuli following alcohol exposure and subsequent abstinence. This may compound interpersonal problems in people with AUD and limit their capacity to seek out or receive social support. Therefore, understanding the neurobiological mechanisms mediating alcohol’s effects on social behavior is required to inform future treatments aimed at enhancing social functioning and reducing relapse in patients with AUD. Drinking in the Dark (DiD) is a robust paradigm for investigating the circuit and molecular mechanisms of binge-like alcohol consumption on physiology and behavior in rodents. In addition, the 3-chamber sociability model permits the interrogation of both social reward and social recognition behaviors following alcohol consumption. Serotonin (5-Hydroxytryptamine, 5-HT) receptor signaling in the lateral habenula (LHb) has been implicated in the development of negative emotional states associated with abstinence from alcohol, but the LHb remains highly understudied in the context of AUD. I recently found that DiD reduced social recognition selectively in female mice during abstinence, and that genetic deletion of the LHb Gq-protein coupled serotonin receptor 5HT2c partially prevented this effect. My preliminary data suggests that binge alcohol consumption enhances the intrinsic excitability of LHb 5HT2c-containing neurons (LHb5HT2c) in the medial sub- region, that 5-HT is released onto LHb5HT2c during social interaction, and that acute engagement of Gi signaling in LHb5HT2c can normalize social deficits induced by alcohol. Moreover, DiD appears to modulate the expression of multiple 5-HT receptor subtypes co-expressed in LHb5HT2c. Together, these data suggest that excessive activation of LHb5HT2c via dysregulation of 5-HT receptor signaling may underlie social deficits induced by alcohol. Using these preliminary findings as a foundation for the current proposal, I will 1) characterize how DiD alters the translational and physiological landscape of LHb5HT2c projecting to the DRN (5HT2cLHb-DRN) and 2) investigate the functional impact of genetic manipulation of 5-HT receptor sub-types in 5HT2cLHb-DRN on neuronal physiology and DiD-induced dysregulation of social behavior. Together, these experiments will determine the effects of binge alcohol drinking on molecular and physiological processes in 5HT2cLHb-DRN and identify novel mechanisms by which these neurons promote social dysfunction during abstinence. Furthermore, this award will provide me with valuable technical and professional training that will facilitate my transition to independence.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15182", "attributes": { "award_id": "1R01GM155729-01", "title": "Zwitterionic polyethylene glycol for therapeutic delivery", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 31602, "first_name": "Sailaja", "last_name": "Koduri", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-05", "end_date": "2026-06-30", "award_amount": 318457, "principal_investigator": { "id": 27922, "first_name": "Hao", "last_name": "Cheng", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 377, "ror": "https://ror.org/04bdffz58", "name": "Drexel University", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Biologic drugs and nanomedicines with conjugated polyethylene glycol (PEG) show extended circulation in the blood, increasing therapeutic efficacy. The U.S. FDA has approved more than 30 PEGylated biologics, including proteins, nucleotides, and peptides, and a few PEGylated nanomedicines, for example COVID-19 mRNA vaccines. Attached PEG chains increase the hydrodynamic radiuses of these therapeutics to reduce their renal clearance during blood circulation. More importantly, PEG conceals therapeutics from immune cells by repelling plasma proteins, rendering therapeutics stealth behavior. The adsorption of a few types of plasma proteins onto therapeutics can lead to the removal of therapeutics by immune cells. PEG chains are hydrophilic and flexible. They can repel plasma proteins through a thermodynamic-driven entropic repulsion. Despite the unique advantage, the application of PEGylated therapeutics is limited by the presence of anti-PEG antibodies (aPEG Abs). These antibodies not only accelerate the clearance of PEGylated therapeutics and attenuate their efficacies but may also cause severe side effects. Varied percentages of populations were found to have pre- existing aPEG Abs in different studies, with the percentage as high as 40%. The high prevalence is likely due to the broad use of PEG in cosmetic and healthcare products. To further improve the pharmacokinetics of therapeutics and circumvent the problem of aPEG Abs, researchers have strived to find PEG alternatives. Among these alternative polymers, zwitterionic polymers have attracted the most attention. In contrast to PEG, zwitterionic polymers repel protein adsorption by forming a hydration layer around the polymers. We hypothesize that zwitterionic PEG (ZPEG) that combines the advantageous characteristics of both PEG and conventional zwitterionic polymers will be superior to them in extending the circulation of therapeutics and minimize the generation of anti-ZPEG antibodies. To develop a ZPEG to replace PEG for therapeutic delivery, we propose the following research plans: 1) synthesize and characterize ZPEG with different chemical structures and reveal the mechanism of enhanced blood circulation of ZPEG-modified proteins; 2) investigate the immunogenicity of ZPEG; 3) investigate the pharmacokinetics and immune responses of nanoparticles covered with ZPEG. Because of the broad application of PEG, an excellent PEG replacement will generate tremendous societal impact. This project will pave the way to replace PEG with ZPEG in therapeutic delivery for minimized side effects and consistent efficacy.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15337", "attributes": { "award_id": "1R21AI183188-01A1", "title": "Structural investigations of coronavirus spike protein", "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": 27781, "first_name": "Mary Katherine Bradford", "last_name": "Plimack", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-26", "end_date": "2026-08-31", "award_amount": 247750, "principal_investigator": { "id": 28219, "first_name": "Syed Saif", "last_name": "Hasan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 793, "ror": "", "name": "UNIVERSITY OF MARYLAND BALTIMORE", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "The spike (S) protein decorates the surface of coronavirus (CoV) particles such as SARS-CoV-2 and enables CoV's to enter and infect host cells. The S protein is the immunogen in genetic and subunit vaccines against COVID-19, which were critical in controlling the COVID-19 global pandemic. In cells that are infected with CoV's or have received a genetic vaccine, the S protein is synthesized in the mammalian cell endoplasmic reticulum (ER), and then trafficking via the secretory pathway consisting of ER, Golgi network, and plasma membrane (PM). This secretory trafficking of S is bidirectional between ER and Golgi, which are the secretory organelles that provide the enzymatic machinery for post-translational modifications, remodeling, and maturation. This includes enzymes for N-glycosylation, which modulates S folding, viral entry, and interactions with the host immune system. Structure-function investigations have shown that N-glycans modulate conformations of S domains, such as the immunogenic receptor binding domain (RBD). Therefore, S N-glycans play a direct role in immune response modulation. As such, N-glycan maturation changes in S due to tissue-, population-, ethnicity- , and age-specific differences in biosynthetic machinery have the potential to dramatically alter infection CoV outcomes and genetic vaccine immunogenicity. Yet little is known about the atomic-level consequences of N- glycan maturation on S structure-function. This is mainly due to the inability to arrest S in various stages of trafficking and N-glycan maturation. In this grant application, we will use an innovative new methodology to control S trafficking. Purified samples of these novel S constructs will be structurally characterized using latest cryoEM and computational tools and assayed for interactions with highly potent conformation-sensitive antibodies. This will generate unprecedented and the first insights into structural modulation of S conformations and epitopes by N-glycan maturation. Collectively, these investigations will be highly significant in providing fundamental insights into secretory trafficking and the role of bidirectional trafficking of S in modulating N-glycan maturation and RBD conformations. These data will open avenues for the design of a new generation of S-based vaccines with improved immunogenicity. In the future, the insights from this research will serve as a platform to inform the design of vaccines against enveloped viruses that pose global health challenges such as HIV and influenza, which utilize the host cell ER-Golgi-PM secretory pathway to acquire immunity evading glycans.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15010", "attributes": { "award_id": "5P01HL162607-02", "title": "Mechanisms Regulating Lung Injury and Early Lung Fibrosis", "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": 22589, "first_name": "CHRISTIAN RENE", "last_name": "Gomez", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-01", "end_date": "2028-06-30", "award_amount": 2374569, "principal_investigator": { "id": 27613, "first_name": "David Albert", "last_name": "Schwartz", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 784, "ror": "https://ror.org/02hh7en24", "name": "University of Colorado Denver", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "The overall goal of this Program is to understand the role of MUC5B in establishing a vulnerable lung and the transition of a vulnerable lung to a lung characterized by persistent injury of bronchoalveolar epithelia and activation of lung fibroblasts. While our findings have identified a novel molecule (MUC5B) and target (bronchoalveolar epithelia) for IPF, only ≈5% of individuals with this genetic variant develop usual interstitial pneumonia (UIP) on HRCT scan, suggesting the need for another insult (a ‘second hit’) to initiate and intensify the fibroproliferative process. Based on our preliminary findings, we postulate that while overexpression of MUC5B places individuals at risk of developing IPF by causing persistent homeostatic ER stress of bronchiolar epithelia, fibroblast recruitment and pro-fibrotic programming requires a second hit to the bronchiolar epithelia resulting in detrimental ER stress and recruitment and activation of fibroblasts. Our Program includes 3 Scientific Projects and 4 Cores, and our unifying scientific themes include: 1) IPF is initiated by enhanced expression of MUC5B (first hit) that establish a vulnerable lung characterized by persistent homeostatic ER stress (without substantial UPR or apoptosis); 2) secondary injury to the bronchoalveolar epithelia results in transition of a vulnerable lung to a lung characterized by detrimental ER stress (involving substantial UPR and apoptosis) and the development of microscopic bronchiolar-centric fibroproliferation; and 3) understanding etiologic and initial biological responses in distal airway epithelia and AEC2 cells, and the interaction of bronchoalveolar epithelia with lung fibroblasts will create opportunities for disease prevention and early intervention. The overarching hypothesis of our Program is that the development of IPF requires two hits, MUC5B overexpression in bronchiolar epithelia that induces a homeostatic, priming response and subsequent injury of the bronchiolar epithelia that results in detrimental ER stress, aberrant epithelia, and fibroblast activation. Project 1 will definitively address the drivers of MUC5B overexpression, Project 2 will identify the determinants of epithelial injury and detrimental ER stress, and Project 3 will investigate the molecular interface between MUC5B-induced epithelial injury and fibroblast activation. At the completion of this highly integrated Program, we will have: 1) established the basic molecular mechanisms that regulate MUC5B-induced injury/repair process in fibroproliferation; 2) defined mechanisms that will create a roadmap for primary and secondary intervention in IPF; and 3) provided a rationale and targets for early intervention in a disease that remains a significant public health problem and may increase post-Covid.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15322", "attributes": { "award_id": "1R35GM155224-01", "title": "Observational causal inference with infectious disease outcomes", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 31916, "first_name": "Guoqin", "last_name": "Yu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-15", "end_date": "2029-07-31", "award_amount": 382852, "principal_investigator": { "id": 31917, "first_name": "Alyssa", "last_name": "Bilinski", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 222, "ror": "https://ror.org/05gq02987", "name": "Brown University", "address": "", "city": "", "state": "RI", "zip": "", "country": "United States", "approved": true }, "abstract": "Infectious disease is a leading cause of global morbidity and mortality. Transmission dynamic models have played a critical role in guiding interventions related to many infectious pathogens, including HIV, influenza, SARS-CoV-1, ebolaviruses, SARS-CoV-2, and mpox. Models project how potential interventions (e.g., non- pharmaceutical measures, therapeutics, and vaccines) may affect disease future transmission. However, they often rely on small scale studies to project effects, and there have been growing concerns that models may produce inaccurate, overly optimistic estimates of population-level intervention effectiveness. Observational causal inference models, which measure intervention effectiveness in real-world settings, could help address this limitation, but applying these to infectious disease is not straightforward. Observational approaches, such as difference-in-differences and synthetic control methods, estimate the impact of an intervention based on empirical counterfactuals: comparing outcomes of interest between treated units or places and similar untreated units. While well-understood with linear outcomes, they can produce biased and misleading results in the context of nonlinear transmission dynamics. Even where observational models perform well, it further remains challenging to transport estimates to new settings to project the impact of future interventions. To address these issues, this project will develop comprehensive theoretical architecture for synthesizing transmission dynamic models with observational causal inference models – employing empirical counterfactuals while accounting for complex biological and population dynamics. In the retrospective workstream, I will propose robust specifications for observational causal inference models that can estimate unbiased treatment effects in policy evaluations using infectious disease outcomes. I will also develop model selection and decision-analytic methods to address potentially significant parameter uncertainty. In the prospective workstream, I will develop approaches to generalize estimates from observational causal inference models to new settings using transmission dynamic models and update projected effects in real-time based on local surveillance indicators. I will illustrate the implications of our methods by re-analyzing prior studies on COVID-19 as well as applying them to answer new questions about respiratory illness control, in collaboration with partners in state and local public health institutions. Across both workstreams, I will develop and disseminate open-source public tools and software to facilitate adoption of these methods. Overall, this work will produce a suite of methodological innovations to improve understanding of the impact of past policies and the accuracy of future projections, while also supporting their implementation in public health institutions to guide planning and priority setting.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15049", "attributes": { "award_id": "5R21AI178151-02", "title": "Large-scale compatibility assessments between ACE2 proteins and diverse sarbecovirus spikes", "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": 27781, "first_name": "Mary Katherine Bradford", "last_name": "Plimack", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-06-23", "end_date": "2025-05-31", "award_amount": 201250, "principal_investigator": { "id": 27646, "first_name": "Kenneth A", "last_name": "Matreyek", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 497, "ror": "https://ror.org/051fd9666", "name": "Case Western Reserve University", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "Viral spillover from animal reservoirs into humans can decimate public health systems and cripple the world economy, as evident with the current SARS-CoV-2 pandemic. Continued wildlife habitat destruction, human expansion, and routine global travel keep increasing the likelihood that another viral pandemic will occur again within the next few decades. Beta coronaviruses are an incredibly diverse family of viruses observed across Asia, Europe, and Africa, that have proven capable of zoonotic spillover into humans as they have caused multiple worldwide outbreaks over the last two decades. We still lack the fundamental understanding of the molecular and genetic factors that dictate the molecular compatibilities that determine which beta coronaviruses are most likely to jump into humans in the future. The ability of SARS-like beta coronaviruses to utilize ACE2 as a receptor for cell entry is a major factor determining the extent of coronavirus tropism across species or within the tissues of an organism. While SARS-CoV-2 has been heavily studied, almost nothing is known about most other members of this virus family. Traditional studies can only test a handful of conditions at a time, incompletely sampling the vast range of relevant experimental conditions, particularly for the hundreds of uncharacterized beta coronaviruses. Large- scale, minimally-biased, cell-based entry assays are needed to model how these factors converge to dictate the probability of infection. We will pair new methods in cell engineering and synthetic biology with DNA-sequencing enabled multiplex genetic assays to perform a series of large-scale infection assays revealing the factors determining susceptibility to beta coronavirus entry. These large-scale experiments will reveal how ACE2 sequence and cell surface density impact the efficiency of virus entry. By testing a library of receptor binding domain sequences identified from ecological surveillance of bat coronaviruses, we will identify which viruses possess sufficient affinity to human ACE2 to potentiate cross-species transmission, and create a catalog describing all of the different ways these viruses have evolved their sequences to engage ACE2. By modeling the relationship between spike and ACE2 protein sequence, expression level, and efficiency of cell entry, we will identify potential animal reservoirs for SARS-CoV-2 and other SARS-like bat coronaviruses, and predict which viruses have sufficient binding with human ACE2 to potentially spark the next pandemic.", "keywords": [ "2019-nCoV", "ACE2", "Affinity", "Africa", "Amino Acid Sequence", "Amino Acids", "Animals", "Arenavirus", "Asia", "Bar Codes", "Binding", "Biological Assay", "Biology", "Biotechnology", "COVID-19 pandemic", "Catalogs", "Cell surface", "Cells", "Chiroptera", "Complex", "Computer Models", "Coronavirus", "Coronavirus spike protein", "DNA sequencing", "Data", "Data Analyses", "Disease Outbreaks", "Europe", "Event", "Family", "Filovirus", "Flow Cytometry", "Future", "Genetic", "Genetic study", "Goals", "Habitats", "Health system", "High-Throughput Nucleotide Sequencing", "Human", "Infection", "Integration Host Factors", "Learning", "Libraries", "Light", "Machine Learning", "Mammals", "Merbecovirus", "Methods", "Modeling", "Modernization", "Molecular", "Organism", "Orthologous Gene", "Pattern", "Plasmids", "Play", "Predisposition", "Probability", "Proteins", "Public Health", "Receptor Cell", "Research Infrastructure", "Role", "SARS-CoV-2 spike protein", "Sampling", "Sarbecovirus", "Series", "Severe Acute Respiratory Syndrome", "Testing", "Time", "Tissues", "Training", "Travel", "Tropism", "Variant", "Viral", "Virus", "Work", "Zoonoses", "betacoronavirus", "cellular engineering", "cross-species transmission", "data access", "density", "experimental study", "future pandemic", "genetic information", "improved", "insight", "interest", "luminescence", "member", "mutant", "mutation screening", "pandemic disease", "prevent", "receptor", "receptor binding", "synthetic biology", "tool", "viral pandemic", "zoonotic spillover" ], "approved": true } } ], "meta": { "pagination": { "page": 3, "pages": 1405, "count": 14046 } } }