Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1383&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=1397&sort=-other_investigators", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=-other_investigators", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1382&sort=-other_investigators" }, "data": [ { "type": "Grant", "id": "10530", "attributes": { "award_id": "1C06OD032035-01A1", "title": "A New Biomedical Research Vivarium at a Hispanic-Serving Institution on the US-Mexico Border", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 23882, "first_name": "CHARLES ASHLEY", "last_name": "Barnes", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-09-19", "end_date": "2027-05-31", "award_amount": 7084640, "principal_investigator": { "id": 26540, "first_name": "Luis A", "last_name": "Cifuentes", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1173, "ror": "", "name": "NEW MEXICO STATE UNIVERSITY LAS CRUCES", "address": "", "city": "", "state": "NM", "zip": "", "country": "United States", "approved": true }, "abstract": "Animal-based biomedical research is a critical contributor to human health and economic well-being in the United States. The importance of animal-based biomedical research has never been more apparent than during the current COVID19 pandemic. Work with animal models has been essential for understanding disease progression, improving patient care, designing and testing vaccines and uncovering the origins of this deadly disease. The current pandemic has also unmasked the grave health disparities that exist in our nation. The disproportionate impact of COVID19 on African-American, Hispanic and Native American populations has highlighted a fundamental gap in our knowledge of how minority populations differ from majority populations in susceptibility, symptomology, and response to treatments for diseases. This knowledge gap extends beyond COVID 19 to encompass virtually all health and behavioral issues. One important solution for addressing this gap is to increase the scope of research, and research training, in communities with larger minority populations. New Mexico State University (NMSU) is a Hispanic-serving Institution of Emerging Excellence located on the southern border of the United States, an area of high racial, cultural and economic diversity. This project would fund construction of new wild animal vivarium, aviary and insectary at NMSU that would enhance biomedical research and training for these diverse populations. This new building would house both wild animal disease models such as rodents, bats and birds and invertebrate disease vectors such as mosquitoes, ticks, and bedbugs. The building will also include behavioral observation and procedural rooms, analytical and physiology testing labs, a microscopy room and support space. This new building will adjoin and complement a new lab animal vivarium already under construction with state bond funding that includes housing for lab animal models, behavioral and procedure rooms, diagnostic and analytical labs, a large surgery suite and support space. The combined complex, called the Biomedical Research Facility, will replace and greatly expand upon the existing aging campus vivarium, and will bring together in one facility work on invertebrate models that is currently spread across campus. The Biomedical Research Facility will support NMSU’s biomedical research strengths in emerging infectious diseases, aging, cancer and health disparities in underserved populations, enhance training of students from underrepresented populations, and promote research addressing the health of border communities and minority populations in New Mexico and the region.", "keywords": [ "Address", "African American", "Aging", "Animal Disease Models", "Animal Model", "Animals", "Area", "Bedbugs", "Behavioral", "Biomedical Research", "Birds", "Border Community", "COVID-19", "COVID-19 impact", "COVID-19 pandemic", "Chiroptera", "Communities", "Complement", "Complex", "Culicidae", "Diagnostic", "Disease", "Disease Progression", "Disease Vectors", "Economics", "Emerging Communicable Diseases", "Funding", "Health", "Hispanic Americans", "Hispanic-serving Institution", "Housing", "Human", "Invertebrates", "Knowledge", "Mexico", "Microscopy", "Minority Groups", "Modeling", "Native Americans", "New Mexico", "Operative Surgical Procedures", "Patient Care", "Personal Satisfaction", "Physiology", "Population", "Population Heterogeneity", "Predisposition", "Procedures", "Research", "Research Training", "Rodent", "Testing", "Ticks", "Underrepresented Populations", "Underserved Population", "United States", "Universities", "Wild Animals", "Work", "base", "behavior observation", "cancer health disparity", "design", "health disparity", "health economics", "improved", "pandemic disease", "research facility", "student training", "treatment response", "vaccine evaluation", "virtual" ], "approved": true } }, { "type": "Grant", "id": "10532", "attributes": { "award_id": "1R43OH012414-01", "title": "Antiviral Polymers for Development of Rapid Reuse, Next Generation PPE", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [ { "id": 25093, "first_name": "Marcienne", "last_name": "Wright", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-09-15", "end_date": "2023-03-15", "award_amount": 243500, "principal_investigator": { "id": 26543, "first_name": "John", "last_name": "Cowart", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1938, "ror": "", "name": "SEACOAST SCIENCE, INC.", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The ability of face masks and other forms of personal protective equipment (PPE) to reduce and/or prevent the possibility of cross-infection and transmission is of critical importance in occupational environments where aerosolized pathogens may be encountered (ie. COVID-19 intensive care units, etc.). Because viruses and microorganisms can survive on surfaces for a few hours to several days, respirator masks and other forms of PPE that have been contaminated with pathogens can become secondary sources of infection for the wearer and others, thus limiting them to single use. In recent months, this has led to N95 respirator shortages worldwide and an undeniable public plea from our nation’s medical professionals for better PPE resources to help mitigate the dangers of viral cross-infection from contaminated PPE in their high-risk occupational environments. There is an urgent moral obligation for the science and business community to develop the next-generation of anti- viral resources to protect the occupational safety of professionals on the frontlines of this and future pandemics. Towards that aim, Seacoast Science, Inc. in collaboration with Professor Dave Spivak (APTEC) propose the co-development of antiviral polymer coatings for application in rapid reuse PPE. Leveraging a known salt crystallization mechanism, proven to kill pathogens via hydration and subsequent recrystallization from human breath, we hypothesize the use of a modified polymeric salt will equally provide SARS CoV-2 inactivation while enhancing mechanical properties for improved compatibility with melt blown fibers of N95 masks vs. table salt. We will develop Polyethyleneimine (PEI) branched polymers with increased osmotic pressure and high antiviral activity that are adhered to a substrate of activated charcoal (AC) to tune polymer loading and filter pore size. This smart, responsive materials system can be used to modify the blown-polymer fiber filters used in N95 masks and/or deposited as anti-viral coatings on other forms of PPE. The proposed technology is anticipated to extend the useful lifetime of N95 masks beyond the single use recommendation, affording protection over multiple uses. In phase I, Seacoast will establish proof-of-concept that the proposed system can be applied to N95 respirators to augment virus negation and increase mask lifetime. Anti-viral polymers will be synthesized utilizing facile, modular, high-yielding chemistry that is compatible with scalable, multi-gram batches and low-cost solution processing. These polymers will be solution deposited onto the blown-polymer fiber filters used in N95 masks, which have been surface-treated with AC. We will evaluate the geometric, mechanical, and hygroscopic behavior of these novel materials, demonstrating their capacity to induce osmotic effects (vs. non-polymeric salt solutions) across membranes structurally analogous to viral envelopes. Seacoast will down-select the top material(s) from these initial experiments and test them against viable COVID analogues in a regulated BSL3 lab to demonstrate efficacy. The proposed virus negating materials are anticipated to facilitate the advent of rugged, anti-viral coatings for the next-generation of rapid-reuse PPE for SARS CoV-2 and emerging variants (delta, mu, etc.).", "keywords": [], "approved": true } }, { "type": "Grant", "id": "10533", "attributes": { "award_id": "1R01AI174515-01", "title": "Dynamic virus-driven remodeling of ER-mitochondria contacts", "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": 22533, "first_name": "Christopher E.", "last_name": "Beisel", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-09-19", "end_date": "2027-07-31", "award_amount": 419426, "principal_investigator": { "id": 26544, "first_name": "Ileana M.", "last_name": "Cristea", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 191, "ror": "https://ror.org/00hx57361", "name": "Princeton University", "address": "", "city": "", "state": "NJ", "zip": "", "country": "United States", "approved": true }, "abstract": "Viruses have evolved elegant strategies to manipulate host cell machinery and rewire core cellular pathways to facilitate productive infection, including enhancing metabolic output and maintaining cell viability. To accomplish this, viruses exert an extensive network of dynamic molecular interactions with cellular organelles. As the functions of organelles are intimately associated with the regulation of their composition, shape, and localization, the control of organelle structure-function relationships is at the core of clarifying the outcome of an infection. While many examples of virus-induced organelle remodeling have been described, very little is understood about how organelle structures engender specific functions. Our lab has characterized a previously unrecognized aspect of viral infection, which is that human viruses globally control organelle remodeling by dramatically rewiring inter- and intra-organelle membrane contact sites (MCS). Using a hybrid quantitative proteomics and super resolution microscopy approach, we demonstrated exquisite reorganization in MCS networks engaged by a broad range of human viruses, including both ancient (herpesviruses) and rapidly adapting (influenza and beta- coronavirus) viruses. We further discovered that infection with the ubiquitous herpesvirus human cytomegalovirus (HCMV) triggers a new specialized MCS structure, mitochondria-ER encapsulations that we termed MENC. We determined that HCMV infection drives predominantly fission at the mitochondrial periphery, and that the fragmented mitochondria enter MENCs and retain their bioenergetic activity. How the infection induces MENC formation and the function of this newly reported structure remain unknown. We propose that MENCs provide a unifying explanation for the longstanding paradox of how certain viruses such as HCMV increase mitochondrial bioenergetic output, despite inducing mitochondrial fragmentation. Our central hypothesis is that HCMV remodels inter- and intra-organelle connections, generating MENCs, which act to protect and stabilize the bioenergetic capacity of fragmented mitochondria. Using a multidisciplinary approach that combines molecular virology with cutting-edge approaches in quantitative proteomics, live super resolution microscopy, ultrastructural electron microscopy, metabolomics, and lipidomics, in Aim 1, we will define the mechanisms underlying the formation and function of MENCs during HCMV infection. In Aim 2, we will establish what signaling cues from HCMV-induced three-way contacts among the ER, mitochondria, and lysosome stimulate peripheral mitochondria fission and elevate bioenergetic respiration. In Aim 3, we will characterize the viral factors that coordinate ER-mitochondria MCS rewiring. Collectively, our study will link newly discovered aspects of virus-orchestrated MCS networking to new two-way and three-way organelle structure-function relationships that underlie fundamental cellular mechanisms, including mitochondrial bioenergetics and autophagic turnover. In doing so, our study will open research areas in how viruses exploit the functional capacities of remodeled organelles for infection, which have broad implications for viral pathogenesis and metabolic disorders.", "keywords": [ "Acetylation", "Activities of Daily Living", "Address", "Area", "Binding", "Bioenergetics", "Biogenesis", "Biological Assay", "Biological Process", "Cell Respiration", "Cell Survival", "Cells", "Coupled", "Crista ampullaris", "Cryo-electron tomography", "Cues", "Cytomegalovirus", "Cytomegalovirus Infections", "Daughter", "Depressed mood", "Electron Microscopy", "Electron Transport", "Event", "Herpesviridae", "Hour", "Human", "Hybrids", "Image", "Immune response", "In Situ", "Infection", "Influenza", "Inner mitochondrial membrane", "Lamins", "Ligation", "Link", "Lipids", "Lysosomes", "Mass Spectrum Analysis", "Membrane", "Metabolic", "Metabolic Diseases", "Metabolism", "Microscopy", "Mitochondria", "Modeling", "Molecular", "Molecular Virology", "Morphogenesis", "Nuclear", "Organelles", "Outcome", "Output", "Oxidative Phosphorylation", "Oxygen Consumption", "Pathology", "Pathway interactions", "Peripheral", "Population", "Production", "Proteins", "Proteomics", "Regulation", "Reporting", "Research", "Resolution", "Respiration", "Role", "Shapes", "Signal Transduction", "Site", "Structure", "Structure-Activity Relationship", "Viral", "Viral Pathogenesis", "Viral Physiology", "Viral Proteins", "Virion", "Virus", "Virus Diseases", "Work", "betacoronavirus", "genetic manipulation", "interdisciplinary approach", "light microscopy", "lipidomics", "live cell microscopy", "metabolomics", "mitochondrial membrane", "peroxisome", "recruit", "release of sequestered calcium ion into cytoplasm", "respiratory", "spatiotemporal", "virology" ], "approved": true } }, { "type": "Grant", "id": "10534", "attributes": { "award_id": "1R01AI163118-01A1", "title": "Analyzing the potential for future bat coronavirus emergence in Myanmar, Laos, and Vietnam", "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": 6011, "first_name": "Erik J.", "last_name": "Stemmy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-09-21", "end_date": "2027-08-31", "award_amount": 653392, "principal_investigator": { "id": 860, "first_name": "Peter", "last_name": "Daszak", "orcid": null, "emails": "[email protected]", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 234, "ror": "", "name": "Ecohealth Alliance inc.", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1939, "ror": "", "name": "ECOHEALTH ALLIANCE, INC.", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "1 Two major coronaviral diseases of wildlife origin have emerged in Asia in the last two decades. Both likely 2 began as zoonotic spillover events, leading to small case clusters, but were not identified until significant 3 community spread made control difficult, and in the case of COVID-19, led to a pandemic. Our prior work and 4 preliminary data show that Southeast Asia has a high diversity of wildlife coronaviruses (CoVs), a large 5 proportion of the population with frequent occupational and environmental exposure to wildlife, and limited 6 surveillance at rural sites where outbreaks likely begin. Our hotspots risk mapping suggests countries directly 7 to the south of China; Myanmar, Laos and Vietnam in particular; contain regions with human-wildlife interfaces 8 and likely regular spillover of novel CoVs from bats and other wildlife. Our preliminary field studies have 9 identified novel viruses related to known zoonoses in bats and other wildlife from each of these countries and 10 communities with serological evidence of novel CoV exposure. The overarching goal of our work is to analyze 11 the behavioral and environmental risk factors for spillover of novel CoVs, identify wildlife-to-human spillover 12 events, assess the risk and drivers of community transmission and spread, and test potential public health 13 interventions to disrupt spillover and spread. To achieve this, we propose the following: 14 Specific Aim 1) community-based surveys and biological sampling of people frequently exposed to wildlife in 15 Myanmar, Laos, and Vietnam, to find serological evidence of spillover and assess behavioral, social structure, 16 spatial connectivity and mobility factors that lead to exposure, spillover, and spread; 17 Specific Aim 2) sampling and PCR screening of bats and other wildlife at community surveillance sites to 18 identify viruses and hosts related to the human infections detected in Aim 1; full genome sequencing and cell 19 entry assays to assess ability to infect human cells; machine learning approaches to estimate zoonotic 20 potential of each novel CoV; 21 Specific Aim 3) syndromic PCR-based surveillance in clinics to identify ‘cryptic’ cases or case clusters caused 22 by bat-CoVs; contact tracing to assess whether cases represent initial spillover or community spread events. 23 Our results will provide detailed information on the risk of future CoV spillover and spread and will inform 24 potential public health interventions to reduce spillover risk and outbreak potential. They may also provide data 25 on wildlife reservoirs and community spillover events of relevance to the origin of COVID-19. Finally, we will 26 rapidly supply viral sequences and isolates for use in vaccine and therapeutic development, including 27 “prototype pathogen” vaccines, via an existing MOU with the NIAID-CREID network. Our long-term goal is that 28 this work will act as a model to build pandemic preparedness strategies to better predict sites and communities 29 where wildlife-origin viruses are likely to emerge, and to disrupt emergence in EID hotspots around the world. 30", "keywords": [ "2019-nCoV", "Affect", "Animal Model", "Animals", "Antibodies", "Asia", "Behavior", "Behavioral", "Biological", "Biological Assay", "COVID-19", "COVID-19 test", "COVID-19 therapeutics", "Cell Culture Techniques", "Cells", "China", "Chiroptera", "Clinic", "Communities", "Contact Tracing", "Coronavirus", "Coronavirus Infections", "Country", "Data", "Disease", "Disease Outbreaks", "Environmental Risk Factor", "Environmental and Occupational Exposure", "Enzyme-Linked Immunosorbent Assay", "Event", "Exposure to", "Frequencies", "Future", "Goals", "Human", "Immunoprecipitation", "Infection", "Intervention", "Laos", "Lead", "Luciferases", "Machine Learning", "Maps", "Measures", "Modeling", "Myanmar", "National Institute of Allergy and Infectious Disease", "Persons", "Population", "Probability", "Public Health", "Publishing", "Questionnaires", "Risk", "Rural", "Sampling", "Serology", "Serology test", "Serum", "Severe Acute Respiratory Syndrome", "Site", "Southeastern Asia", "Surveys", "Syndrome", "System", "Testing", "Vaccines", "Variant", "Vietnam", "Viral", "Virus", "Western Blotting", "Work", "Zoonoses", "animal coronavirus", "base", "community clinic", "community transmission", "coronavirus disease", "design", "disease transmission", "field study", "genome sequencing", "high risk", "molnupiravir", "novel", "novel coronavirus", "novel virus", "pandemic disease", "pandemic preparedness", "pathogen", "prototype", "public health intervention", "public health relevance", "remdesivir", "screening", "social structure", "spillover event", "therapeutic development", "vaccine candidate", "vaccine development", "whole genome", "zoonotic spillover" ], "approved": true } }, { "type": "Grant", "id": "10536", "attributes": { "award_id": "263201800029I-0-759802200012-1", "title": "UNEQUAL TREATMENT REVISITED: THE CURRENT STATE OF RACIAL AND ETHNIC DISPARITIES IN HEALTH CARE", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Drug Abuse (NIDA)", "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)", "Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)" ], "program_reference_codes": [], "program_officials": [], "start_date": "2022-09-28", "end_date": "2024-09-27", "award_amount": 125000, "principal_investigator": { "id": 26548, "first_name": "ROBERT", "last_name": "DAY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 339, "ror": "https://ror.org/038mfx688", "name": "National Academy of Sciences", "address": "", "city": "", "state": "DC", "zip": "", "country": "United States", "approved": true }, "abstract": "The Institute of Medicine’s (IOM, 2003) [Now the National Academy of Medicine as one of the National Academies of Sciences, Engineering, and Medicine, NASEM] groundbreaking report “Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care” documented differences in the quality of healthcare services received by people from racial and ethnic minority groups, highlighting the roles that racial stratification and social inequities play in health outcomes. Published almost 20 years after the landmark Malone-Heckler report, Unequal Treatment provided compelling models and evidence demonstrating how the health care system operates on multiple levels to create, sustain, and increase racial and ethnic health disparities – emphasizing the contributions of factors beyond the control of the individual patient. Reviewing evidence from the 2003 report and data generated subsequently, NASEM will convene an ad hoc expert committee to examine the current state of racial and ethnic disparities in U.S. healthcare. Congress commissioned the IOM in 1999 to study the root causes of racial and ethnic health disparities due to the growing concern around people from racial and ethnic minority groups and people experiencing poverty becoming a “permanent health care underclass.” Due to the historical marginalization of these populations in the healthcare system, high rates of being uninsured or underinsured, along with high health care costs driving differential access, utilization and quality of care, the IOM sought to illuminate how and why key factors impacting healthcare access, utilization and quality of care contributed to health disparities. The foci were two levels of the healthcare system that were hypothesized to contribute significantly to racial and ethnic health disparities. They first examined the operation of healthcare systems and the legal and regulatory climate in which health systems function, providing more nuanced explanations that moved beyond attributing health disparities to differential healthcare access. The second focused on understanding discriminatory practices at the patient, clinician, and health system levels – measured by bias, stereotyping, and clinician/patient concordance – as causes of racial and ethnic health disparities. The report provided actionable recommendations for evidenced-based targeted interventions that could be implemented over time to improve quality of care and reduce racial and ethnic healthcare disparities. The major findings from the IOM report reinforced that healthcare system limitations had particularly negative implications for the quality of care received by Black/African American persons and certain Hispanic/Latino persons based on their birthplace or English language fluency. However, most of the available data at the time was available for Black/African American persons and there was limited information in the IOM report on other minoritized populations. Among other findings, the report concluded that: • Minoritized racial and ethnic patients often receive a lower quality of care and less intensity of indicated treatment and diagnostic services across a wide range of procedures and disease areas. • Insurance status is a key predictor of the quality of care that minoritized racial and ethnic groups receive since they are disproportionately represented in the Medicaid and dual-eligible Medicare categories and no health insurance; yet when insurance status is controlled, race and ethnicity remain significant predictors of quality of care. • Within the clinical encounter, minoritized patients may perceive both overt, as well as subtle forms of discrimination when seeking care. Bias, stereotyping, prejudice, and communication barriers on the part of clinicians and other healthcare staff may be contributory factors to racial and ethnic disparities in healthcare. • Limited assistance with professional interpretation services is available to patients with limited English proficiency, which has negative implications for the clinical encounter. • Sociocultural differences between patient and clinician influence communication and clinical decision making; thus, ineffective communication during the medical encounter may lead to patient dissatisfaction, non-adherence, poorer health outcomes, and subsequently, racial and ethnic disparities in healthcare. • A significant body of literature defines and supports the importance of cross-cultural education in the training of health professionals. Despite several approaches and various opportunities for integration, curricula in this area have been implemented to a modest degree in undergraduate, graduate, and continuing education of health professions. • Medical graduates who identify with an underrepresented minority group made up about 14% in 2019-2020, with 7% being African American, 6% Latino/a and 1% American Indian or Alaska Native and Native Hawaiian or Pacific Islander. The 22% of medical graduates who identify as Asians, include Southeast Asians who are also underrepresented. • More information is needed on the potential impacts of medical care delivered in the context of cultural and linguistic concordance between clinicians and their patients. These would include efforts to evaluate the role of physicians from underrepresented populations and that of international medical graduates and minoritized racial and ethnic populations, and specifically the extent to which this contributes to healthcare disparities. Along with identifying key areas of healthcare that create and sustain racial and ethnic disparities, the IOM report identified areas needed for further research and suggested several intervention strategies to eliminate disparities in quality of care and improve population health. These recommendations included: • Develop a better understanding of the relative contribution of patient, clinician, and institutional characteristics to healthcare disparities. • Further illuminate clinical decision-making, heuristics applied in diagnostic evaluation, and how patients' race, ethnicity, gender, English language fluency, and social class may influence these decisions. • Assess the relative contributions of clinician biases, stereotyping, prejudice, and uncertainty in producing racial and ethnic disparities in diagnosis, treatment, and outcomes of care. • Investigate the roles of non-physician healthcare professionals, including nurses, physician assistants, occupational and rehabilitation therapists, mental health professionals (including psychologists, social workers, and marital and family therapists), pharmacists, allied health professionals, as well as medical assistants, administrative, and laboratory staff in contributing to healthcare disparities. • Due to a paucity of research, assess healthcare disparities among Asian American, Native Hawaiian and Pacific Islander, American Indian and Alaska Native, and Hispanic or Latino populations and their subpopulations. • Assess the potential impacts of medical care delivered in the context of cultural and linguistic concordance between clinicians and their patients. These would include efforts to evaluate the role of physicians from underrepresented populations and that of international medical graduates and minoritized racial and ethnic populations, and specifically the extent to which this contributes to decreasing healthcare disparities. • Develop and test the utility of healthcare improvement of patient-based measures of (1) trust in clinicians and systems and (2) exposure to discriminatory practices by clinicians or systems. • Develop methods for monitoring progress toward reducing and ultimately eliminating racial and ethnic disparities in healthcare. • Understand the relationship between healthcare disparities and the health gap between racial and ethnic minority and White patients stratified by educational attainment. While the IOM report provided the foundational evidence base necessary for subsequent studies to address how healthcare related factors significantly contribute to disparities in healthcare quality for minoritized racial and ethnic persons and the approaches needed to address them, health disparities persist and, in many conditions, continue to widen. It has been 20 years since the publication of the IOM report, and factors outside of the control of the individual continue to play a significant role in disparate health outcomes. Needed is an understanding of the aspects of healthcare quality identified in the IOM report which have shown improvement, promise, or worsened. For example, a significant advancement in health care is the Patient Protection and Affordable Care Act of 2010 (ACA) which has increased insurance coverage for 20 million U.S. residents, reduced the insurance gap across all racial and ethnic groups in the U.S. and completely eliminated the disparity for Asian Americans, Native Hawaiians and Pacific Islanders, but not for other racial groups. 4 Unfortunately, there remains a considerable segment of the population that lacks access to healthcare due to lack of health insurance. The lack of insurance is most notable for Latino/Hispanic populations 18 to 64 years of age. Further, even among insured populations, numerous adverse social determinants of health—such as lack of transportation and paid sick leave—may impede access to care for marginalized groups. In addition, demographic shifts in the population and public health emergencies such as the COVID-19 pandemic have exacerbated racial and ethnic health disparities in all aspects of healthcare and health outcomes. These factors must be taken into consideration when assessing the current disparities landscape. Advancing the work of the previous IOM report will include a review of the state of racial and ethnic disparities in quality of care, access, and utilization, and expand to examine community and population level factors that operate to influence healthcare disparities. Current evidence suggests that the digital divide has hampered the potential of health information technology to expand access to healthcare for socioeconomically disadvantaged groups and racial and ethnic minority persons. 5 For example, in a study that assessed geographic and racial and ethnic disparities in access to care, Mantri & Mitchell (2021) found that with the shift to virtual care due to the COVID-19 pandemic, visits among Black/African American individuals was cut in half relative to pre-pandemic utilization. 6 Other research has also found that the COVID-19 pandemic has had an adverse impact on healthcare utilization due to limited telemedicine adoption7 and increased racial inequities in the quality and intensity of care. 8 Thus, it is important that healthcare systems emphasize access to high quality of care for all, strengthen preventive health care approaches, address social needs as part of healthcare delivery, and diversify the healthcare workforce to more closely reflect the demographic composition of the patient population.", "keywords": [ "Academy", "Acute", "Address", "Affect", "Affordable Care Act", "African American", "African American population", "Age-Years", "Alaska Native", "Ambulatory Care", "American Indians", "Area", "Asian Americans", "Asian population", "Automobile Driving", "Black race", "Budgets", "COVID-19", "COVID-19 pandemic", "Caring", "Categories", "Characteristics", "Chronic", "Climate", "Clinical", "Communication", "Communication Barriers", "Communities", "Congresses", "Consensus", "Continuing Education", "Country", "Data", "Decision Making", "Diagnosis", "Diagnostic", "Diagnostic Services", "Discrimination", "Disease", "Economically Deprived Population", "Education", "Educational Curriculum", "Elderly", "Emergency Care", "Emergency Situation", "Engineering", "English Language", "Ethnic Origin", "Ethnic group", "Evaluation", "Exposure to", "Family", "Focus Groups", "Foundations", "Gender", "Geographic Factor", "Geography", "Graduate Education", "Grant", "Health", "Health Care Costs", "Health Insurance", "Health Occupations", "Health Policy", "Health Professional", "Health Services Accessibility", "Health Services Research", "Health system", "Healthcare", "Healthcare Systems", "Hispanic", "Hispanic Populations", "Hospitals", "Individual", "Inequality", "Infrastructure Activities", "Institute of Medicine (U.S.)", "Insurance", "Insurance Coverage", "International", "Internet", "Intervention", "Knowledge", "Laboratories", "Latino", "Latino Population", "Laws", "Lead", "Legal", "Limited English Proficiency", "Linguistics", "Literature", "Longevity", "Measures", "Medicaid", "Medical", "Medicare", "Medicine", "Mental Health", "Methods", "Minority Groups", "Modeling", "Monitor", "Native Hawaiian or Other Pacific Islander", "Nurses", "Occupational", "Office Management", "Operating System", "Outcome", "Outpatients", "Pacific Island Americans", "Patients", "Persons", "Pharmacists", "Physician Assistants", "Physician&apos", "s Role", "Plant Roots", "Play", "Policies", "Policy Maker", "Population", "Poverty", "Prejudice", "Preventive healthcare", "Primary Health Care", "Procedures", "Psychologist", "Public Health", "Publications", "Publishing", "Quality of Care", "Race", "Recommendation", "Recording of previous events", "Reduce health disparities", "Regulation", "Rehabilitation therapy", "Reporting", "Research", "Research Personnel", "Resources", "Review Literature", "Role", "Series", "Services", "Sick Leave", "Social Class" ], "approved": true } }, { "type": "Grant", "id": "10537", "attributes": { "award_id": "272201700061C-P00009-9999-2", "title": "COVID-19: External Quality Assurance Program Oversight Laboratory (EQAPOL)", "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": [], "start_date": "2022-09-30", "end_date": "2023-09-29", "award_amount": 1787600, "principal_investigator": { "id": 24151, "first_name": "THOMAS", "last_name": "DENNY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 246, "ror": "https://ror.org/00py81415", "name": "Duke University", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 246, "ror": "https://ror.org/00py81415", "name": "Duke University", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "The mission of the Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), is to increase basic knowledge of the pathogenesis and transmission of the human immunodeficiency virus (HIV), support the development of therapies for HIV infection and its complications, and support the development of vaccines and other prevention strategies. Reliable laboratory data are essential to the clinical evaluation of candidate HIV vaccine platforms and immunogens. Data from multiple laboratories performing assays in support of single or multiple vaccine candidate trials must be accurate and reproducible. The purpose of the External Quality Assurance Program Oversight Laboratory (EQAPOL) is to provide confidence that individual laboratories generate reliable data to support HIV vaccine immunogen advancement. EQAPOL supports these efforts by participating in the development and availability of validated assays, providing common and well-characterized reagents and Standard Operating Procedures (SOPs), and providing External Quality Assurance (EQA) programs to measure and monitor laboratory performance. This project will provide external quality assurance program support for laboratories performing immunology assays for COVID-19 Prevention Network (CoVPN)-led vaccine efficacy trials.", "keywords": [ "2019-nCoV", "Acquired Immunodeficiency Syndrome", "Antigens", "Binding", "Biological Assay", "Biometry", "COVID-19", "COVID-19 Prevention Network", "COVID-19 assay", "Data", "Development", "Flow Cytometry", "HIV", "HIV Infections", "HIV vaccine", "Immunology", "Immunology procedure", "Individual", "Knowledge", "Laboratories", "Measures", "Mission", "Monitor", "National Institute of Allergy and Infectious Disease", "Pathogenesis", "Performance", "Prevention strategy", "Procedures", "Reagent", "Reproducibility", "SARS-CoV-2 antibody", "Stains", "United States National Institutes of Health", "cytokine", "data management", "data quality", "design", "efficacy trial", "programs", "quality assurance", "reagent standard", "repository", "research clinical testing", "therapy development", "transmission process", "vaccine candidate", "vaccine development", "vaccine efficacy", "vaccine platform" ], "approved": true } }, { "type": "Grant", "id": "10538", "attributes": { "award_id": "1R18HS028787-01A1", "title": "The Impact of an Adaptive Patient-Centered Web Application on Medication Optimization in HFrEF Patients", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [ { "id": 24555, "first_name": "Mario", "last_name": "Teran", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-09-30", "end_date": "2025-09-29", "award_amount": 999999, "principal_investigator": { "id": 26549, "first_name": "Michael", "last_name": "Dorsch", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Heart failure (HF) is the most common hospital discharge diagnosis among older adults in the United States. Strikingly, 40% of patients are readmitted within 1-year following their first HF admission. This results in significant potentially avoidable costs to our already strained healthcare system, since hospitalizations result in 70% of yearly HF management costs. One of the most common causes of HF readmission is lack of chronic medication optimization. Despite widespread knowledge that guideline-directed medication therapy (GDMT) reduces hospital admission and mortality in HF with reduced ejection fraction (HFrEF, also referred to as systolic heart failure), medications are often not optimized in clinical practice. During the COVID-19 pandemic, missed visits and virtual visits without a physical exam have further disrupted care for HFrEF. The American College of Cardiology recommends the use of electronic health records (EHR) to reduce errors, improve decision support, and facilitate GDMT for HFrEF. Yet currently there are no effective patient centered EHR tools that can assess clinical characteristics and provide adaptive recommendations to optimize GDMT. This represents a significant gap in knowledge that limits the benefits of GDMT. Therefore, there is an immediate need to rigorously test EHR tools that can increase appropriate prescribing of GDMT. This proposed project will determine the effectiveness of an adaptive web application to facilitate GDMT optimization and builds on our work from previous research. Our central hypothesis is that the web application can improve the prescribing of GDMT in HFrEF patients. The rationale for this project is that a new model for disease management – placing patients in control of their condition – will have a substantial impact on HF outcomes. Our objectives are to: (1) determine the effects of an adaptive medication optimization web application on guideline-directed medication prescribing in HF, (2) assess concordance between the recommendations provided by the medication optimization algorithm and the medications prescribed, and (3) identify the patient and provider characteristics that moderate the effectiveness of the medication optimization web application.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "10540", "attributes": { "award_id": "1UG3DA057042-01", "title": "A Randomized Controlled Trial of A Digital, Self-Guided, Avatar Assisted- Cognitive Behavioral Therapy Platform to Treat Addiction: Digital RITch®CBT vs. Standard CBT", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Drug Abuse (NIDA)" ], "program_reference_codes": [], "program_officials": [ { "id": 23140, "first_name": "Will", "last_name": "Aklin", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-09-30", "end_date": "2024-08-31", "award_amount": 804694, "principal_investigator": { "id": 26552, "first_name": "Caroline J.", "last_name": "Easton", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1941, "ror": "https://ror.org/00v4yb702", "name": "Rochester Institute of Technology", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Substance User Disorders (SUDS) and Intimate partner violence (IPV) are devastating to families and society (CT CASE, 2015) costing $700 billion annually in healthcare expenditures for SUDS and $12.6 billion in annual costs for IPV. There is a high co-occurrence of substance use and IPV (IPV; CT CASE, 2015). Rates of SUDS and IPV increased during the Covid-19 pandemic (Dubey et al., 2020) at a time period when access to care was disrupted in the absence of Telehealth or Digital Therapy Platforms. The alarmingly higher rates of SUDS and IPV during the pandemic underscored the need for more clinical research trials for device and digital technology developments (DTx). CBT is an evidence based therapy vehicle that has been shown to be effective in improving treatment outcomes across a number of behavioral health disorders (Dutra et al., 2008) including initial efficacy in treating substance abuse and IPV among male offenders in an individual (1:1) CBT therapy modality (Easton et al., 2017). Recent meta-analytic reviews report that digitized versions of CBT are showing effectiveness in treating a range of maladaptive behaviors (Spek et al., 2007) as well as SUDS (Carroll and colleagues, 2014; Carroll et al., 2008) but are limited digital versions that lack personalization and relevant content to patients self-reported symptom distress. To date, digitized platforms have not been used to treat SUDS and IPV among clients entering substance abuse treatment. Researchers are calling for more RCTs using DTx’s of CBT as a vehicle for healthy behavior change among SUD - IPV clients (Nesset and colleagues, 2019). Given our prior success with CBT to treat both SUDS and IPV across 12 weeks of 1:1 treatment, we extended our integrated CBT therapy to a DTx platform. DTx platforms are advantageous because they are easy to disseminate, cost-effective, lead to increases in clients’ engagement and maximize compliance with practice exercises. The technology that exists today is modernized to allow for personalized therapy content to be linked to reported symptom distress. We developed a 12- week digital, Avatar Assisted, interactive platform, RITch®CBT, as an intervention platform self -guided by patients and for patients to use “at home” to practice coping skill exercises at their convenience. In response to NIH’s PAR 21-183, we propose to conduct a Phase I and II Study: UG3 (Phase I) and UH3 (Phase II) in collaboration with the FDA regarding ongoing feedback and regulatory processes. In Phase I, we propose a feasibility study, a randomized controlled trial to test the efficacy of RITch®CBT among SUD-IPV clients entering addiction treatment comparing it to face to face 1:1 CBT. If efficacy is achieved, an effectiveness study will be performed in Phase II (UH3) to improve treatment outcomes among individuals and their families suffering from co-occurring SUDS and IPV, a common co-occurring problem within families across the U.S.", "keywords": [ "Adverse effects", "Aftercare", "Aggressive behavior", "Alcohols", "Back", "Breath Tests", "COVID-19 pandemic", "Caring", "Centers for Disease Control and Prevention (U.S.)", "Child", "Client", "Clinical Data", "Clinical Research", "Cognitive Therapy", "Coke", "Collaborations", "Computers", "Conflict (Psychology)", "Coping Skills", "DSM-V", "Devices", "Disease", "Distress", "Effectiveness", "Epidemic", "Exercise", "Face", "Family", "Feasibility Studies", "Feedback", "HIV", "Health Expenditures", "Health Services Accessibility", "Home", "Impulsivity", "Individual", "Injury", "Intervention", "Lead", "Link", "Measures", "Mental Depression", "Methods", "Modality", "Modeling", "Modernization", "National Institute of Drug Abuse", "Online Systems", "Outcome", "Outcome Measure", "Participant", "Patient Self-Report", "Patients", "Pharmaceutical Preparations", "Phase", "Post-Traumatic Stress Disorders", "Process", "Protocols documentation", "Questionnaires", "Randomized", "Randomized Controlled Trials", "Recording of previous events", "Regulatory Pathway", "Reporting", "Research", "Research Personnel", "Sampling", "Sexually Transmitted Diseases", "Societies", "Standardization", "Substance Addiction", "Substance Use Disorder", "Substance abuse problem", "Symptoms", "Technology", "Time", "TimeLine", "Toxicology", "Treatment outcome", "United States", "United States National Institutes of Health", "Urine", "Validation", "Visit", "addiction", "base", "behavior change", "behavioral health", "chronic pain", "cost", "cost effective", "craving", "digital", "digital treatment", "distress tolerance", "effectiveness study", "effectiveness testing", "efficacy testing", "ethnic diversity", "evidence base", "gastrointestinal", "improved", "intimate partner violence", "maladaptive behavior", "male", "men", "offender", "pandemic disease", "personalized medicine", "primary outcome", "randomized controlled study", "randomized trial", "reduced substance use", "response", "secondary outcome", "substance abuse treatment", "substance use", "substance user", "success", "technology development", "telehealth", "trait", "treatment comparison", "trial design", "user-friendly" ], "approved": true } }, { "type": "Grant", "id": "10543", "attributes": { "award_id": "1C06OD034121-01", "title": "National Ferret Research and Resource Institute (NFRRI) at University of Iowa", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "NIH Office of the Director" ], "program_reference_codes": [], "program_officials": [ { "id": 23882, "first_name": "CHARLES ASHLEY", "last_name": "Barnes", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-09-20", "end_date": "2027-05-31", "award_amount": 7975000, "principal_investigator": { "id": 26554, "first_name": "JOHN F", "last_name": "ENGELHARDT", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 220, "ror": "https://ror.org/036jqmy94", "name": "University of Iowa", "address": "", "city": "", "state": "IA", "zip": "", "country": "United States", "approved": true }, "abstract": "While genetic mouse models have been the backbone of translational biomedical research for the past four decades, mice often fail to model human disease due to species-specific differences in the cell biology of the affected organs, as well as the evolutionary divergence of their genome. The ferret has proven an excellent species for modeling infectious disease (including SARS-CoV2) and human diseases of the brain, pancreas, and lung when mice have failed. The University of Iowa (UI) is the only location in the world capable of genetically engineering ferrets with multiple precise genetic alterations previously only achievable in mice. This technology has enabled the construction of genetic ferret models capable of fate mapping stem cell compartments (i.e., lineage tracing), modeling human diseases including those with humanized genetic loci, and conditional genetics using Cre recombinase. A federally-funded National Ferret Research and Resource Center was formed eight years ago, which provides services for the creation of new genetic ferret models, performing research studies in ferrets, and the distribution of tissues and cells from existing genetic lines. This national resource has provided services to more than 129 academic investigators,108 of which are outside the UI, and currently has 8 contracts with biotechnology companies seeking to develop therapies for genetic and acquired diseases using ferret models. These services have exceeded the capacity of facilities for both performing research in ferrets and housing ferrets on the UI campus. This proposal seeks to design and construct a research facility that will house the National Ferret Research and Resource Institute (NFRRI) on the UI campus. The proposed facility has been designed to maximize synergy and minimize overlap with existing facilities at UI and will be adjacent and connected to existing ferret expansion housing (referred to as the BSRF facility). The NFRRI will contain state- of-the-art equipment for genetically engineering ferret zygotes and performing research in ferrets. Procedural space will include a USDA-compliant sterile surgical suite and separate microinjection room for model creation. In addition to wet lab research space, specialized procedural suites will accommodate nebulization, pulmonary function testing, and specialized imaging equipment. The NFRRI will primarily provide services to academic investigators outside UI and for-profit biotechnology companies, but will also provide ferret models for research that will occur on the main UI campus in existing research facilities. Furthermore, the chosen location for the facility has adjacent land for future expansion of research space and ferret housing with a long-term strategic plan that recruits next-generation leaders of the NFRRI and capitalizes on existing relationships with for-profit biotechnology companies seeking to develop therapies for human diseases in preclinical ferret models. The short- and long-term strategic goals of the NFRRI will be facilitated through financial partnerships with the University of Iowa (cost sharing of the NFRRI building), Cystic Fibrosis Foundation, and Marshall Farms (the largest breeder of ferrets for research).", "keywords": [ "2019-nCoV", "Affect", "Biomedical Research", "Biotechnology", "Brain Diseases", "Cell Compartmentation", "Cells", "Cellular biology", "Contracts", "Cost Sharing", "Cystic Fibrosis", "Disease", "Drug or chemical Tissue Distribution", "Enterobacteria phage P1 Cre recombinase", "Equipment", "Farm", "Ferrets", "Foundations", "Funding", "Future", "Genetic", "Genetic Engineering", "Genome", "Goals", "Housing", "Image", "Institutes", "Iowa", "Location", "Lung diseases", "Microinjections", "Modeling", "Mus", "Mutation", "Nebulizer", "Operative Surgical Procedures", "Organ", "Pancreatic Diseases", "Pulmonary function tests", "Research", "Research Personnel", "Resources", "Services", "Sterility", "Strategic Planning", "Technology", "United States Department of Agriculture", "Universities", "Vertebral column", "design", "design and construction", "genomic locus", "human disease", "human model", "infectious disease model", "mouse model", "next generation", "pre-clinical", "recruit", "research facility", "research study", "stem cells", "synergism", "therapy development", "zygote" ], "approved": true } }, { "type": "Grant", "id": "10544", "attributes": { "award_id": "1DP2AI175470-01", "title": "Manipulating Epitope Immunodominance and Tracking B-cell-Antigen Interactions for Vaccine Design.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "NIH Office of the Director" ], "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": "2022-09-08", "end_date": "2025-08-31", "award_amount": 1616010, "principal_investigator": { "id": 26555, "first_name": "Amelia", "last_name": "Escolano", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1141, "ror": "", "name": "WISTAR INSTITUTE", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT SUMMARY/ ABSTRACT Infectious diseases are serious and recurrent health threats. Particularly concerning are viruses with the capacity to mutate and generate de novo diversity in short periods of time. These viruses adapt to new hosts and environments, and continuously escape from the host anti-viral immune response. Preventative vaccines are highly desirable; however, no defined guidelines exist for the design of efficacious vaccines against rapidly mutating viruses such as HIV-1, influenza, or the current SARS-CoV2, with multiple different circulating variants. Despite their high diversity, viral variants present conserved regions that are essential for viral fitness and infectivity. These conserved epitopes are their Achilles heels, and the focus of antibody-based vaccine design efforts. A vaccine against a highly mutating virus should elicit an antibody response that specifically targets the conserved regions of the virus, as it would recognize and neutralize the broad diversity of its variants. Significant efforts in the field have focused on engineering viral immunogens to make their conserved epitopes more available for antibody recognition. Unfortunately, targeting antibody responses to specific conserved epitopes of interest is incredibly challenging. Complex antigens, such as viral spike proteins, elicit polyclonal responses dominated by antibodies to non-conserved epitopes. These antibodies have no potential to broadly neutralize the virus, and also interfere with the maturation of broadly protective antibodies in the germinal centers. Aiming to elicit broadly neutralizing antibodies (bNAbs) against a conserved epitope of HIV-1, we recently designed and evaluated a new HIV-1 Envelope (Env)-based priming immunogen, which elicited bNAb-like antibodies against a conserved epitope of Env in wild type mice and macaques; despite this achievement, these antibodies showed no neutralization activity against HIV-1, suggesting that additional immunization would be required to induce bNAbs. Nevertheless, further immunization in macaques elicited a polyclonal antibody response of only limited potency and breadth, dominated by antibodies to non-conserved epitopes of Env. Based on these observations, I hypothesize that reducing interfering antibody responses to non-conserved viral epitopes, and tracking the antibody responses with potential to become bNAbs, will pave the path towards bNAb development and inform vaccine design efforts. In this proposal, we will design and evaluate a novel strategy to modulate epitope immunodominance, which in addition, will allow us to record and track the history of antigen-B-cell interactions in vivo. The proposed technology will be used to customize the immunodominance properties of complex antigens in order to direct the antibody response to the epitopes of interest. In addition, we will use our new technology to barcode B cells responding to multiple immunizations, track their fates and record their history of antigen encounters. This groundbreaking technology will provide very valuable information to elucidate the mechanisms governing the B cell responses to vaccination and infection, and will significantly contribute to establish guidelines for vaccine design.", "keywords": [ "2019-nCoV", "Achievement", "Antibodies", "Antibody Response", "Antigens", "B-Lymphocytes", "Bacteria", "Bar Codes", "Cell Communication", "Communicable Diseases", "Complex", "Custom", "Development", "Engineering", "Environment", "Epitopes", "Guidelines", "HIV-1", "Health", "Immune response", "Immunization", "Infection", "Influenza", "Macaca", "Mutate", "Preventive vaccine", "Property", "Proteins", "Public Health", "Recording of previous events", "Recurrence", "Research", "Structure of germinal center of lymph node", "Technology", "Time", "Vaccination", "Vaccine Design", "Vaccines", "Variant", "Viral", "Virus", "Wild Type Mouse", "base", "design", "in vivo", "interest", "neoantigens", "neutralizing antibody", "new technology", "novel strategies", "pathogen", "polyclonal antibody", "response", "tumor", "viral fitness" ], "approved": true } } ], "meta": { "pagination": { "page": 1383, "pages": 1397, "count": 13961 } } }