Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1391&sort=principal_investigator
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=principal_investigator", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1424&sort=principal_investigator", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1392&sort=principal_investigator", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1390&sort=principal_investigator" }, "data": [ { "type": "Grant", "id": "15403", "attributes": { "award_id": "1K12TR004908-01", "title": "CTSA K12 Program at The University of Texas Health Science Center at Houston", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Center for Advancing Translational Sciences (NCATS)" ], "program_reference_codes": [], "program_officials": [ { "id": 12440, "first_name": "CAROL", "last_name": "MERCHANT", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-25", "end_date": "2029-06-30", "award_amount": 974000, "principal_investigator": { "id": 32004, "first_name": "Charles C", "last_name": "Miller", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32005, "first_name": "JON E.", "last_name": "TYSON", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 788, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "CTSA K12 Program at The University of Texas Health Science Center at Houston: Project Summary / Abstract The COVID pandemic has dramatically highlighted the need for a well-trained and highly adaptable clinical and translational science workforce; especially one that is capable of rapid design and deployment of clinical trials and key capabilities that accelerate research translation. The University of Texas Health Science Center at Houston (UTH-H), UT MD Anderson Cancer Center (MDACC) and their partner institutions across Texas, have collective capabilities and relationships that allow us to meet these profound and diverse career development needs. The K12 emphasizes T2-T4 science, and is based at McGovern Medical School and also serves our Schools of Public Health, Biomedical informatics, Nursing, and Dentistry, MDACC, and our Partners: UT Rio Grande Valley, UT Tyler and Texas Tech El Paso. We propose to fund 5 Scholars per year, with one slot at MDACC and one at a Partner site. To maximize the number and achievements of investigators we train, we will leverage CTSA funding to enhance our program, developing skilled C&T investigators in the Texas Medical Center TMC) (9,200 beds; 10 million encounters per year) and the 3 diverse medical centers that comprise our partners. Our Program includes: 1) the Clinical and Translational (C&T) Research Curriculum (11 required courses/workshops, provided in-person or by video training to each institution); 2) MS Courses & Degree in Clinical Research (optional for Scholars and tailored to an individualized career development plan; and 3) our central focus: the Intensive Mentorship Program, that has been highly successful in helping prior KL2 and other mentees secure major grants, publish in high impact journals, and become institutional and national academic leaders. Special strengths include our Scholars' research success involving multidisciplinary teams and other CTSA hubs; improving the delivery, safety, and effectiveness of healthcare for women, children, and disadvantaged patients of any age; advancing research methods using n-of-1 trials, Bayesian methods, hybrid implementation effectiveness designs and economic analyses; and showing reduced health system costs to secure clinical reimbursements that sustain and expand improved approaches to health care. Next cycle innovations will augment these strengths, specifically train the NCATS-identified translational science competencies, and promote learning health care (LHC) through an expanded LHC consultation service emphasizing comparative effectiveness and dissemination/implementation, studies, a continuous community engagement program, and IRB leadership to facilitate and advance exemplary comparative effectiveness research, trials of emergency therapies, and implementation/de-implementation research. These and other Core features will promote the career development of Scholars within a LHC system to most rapidly advance clinical care and the health of diverse populations. Integration with the UM1, the T32s and the R25 is strong. With these innovations and our track record, infrastructure, and institutional support, CTSA funding will predictably produce a large return by developing innovative, collaborative, rigorous, and productive leaders in C&T science.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15404", "attributes": { "award_id": "1R03AI178380-01A1", "title": "Characterizing the early childhood neurodevelopmental impact of infants exposed to maternal SARS-CoV-2 infection during pregnancy", "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": 6243, "first_name": "BROOKE ALLISON", "last_name": "Bozick", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-16", "end_date": "2026-05-31", "award_amount": 83196, "principal_investigator": { "id": 32006, "first_name": "Leena Bhattacharya", "last_name": "Mithal", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2539, "ror": "", "name": "LURIE CHILDREN'S HOSPITAL OF CHICAGO", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "Pregnant people are uniquely susceptible to SARS-CoV-2 infection, with risks of severe maternal COVID-19 illness and obstetric complications. However, far less is known about the long-term impact of pregnancy- associated SARS-CoV-2 infection on developing infants. Given the global burden, it is estimated that millions of pregnant people have had SARS-CoV-2 infection. Prior work by our Studying Novel Infectious Pathogens in Pregnancy (SNIPP) research team has identified distinct types of SARS-CoV-2-associated injury to the placenta, such as maternal vascular malperfusion and COVID placentitis. Further, we have identified unique inflammatory cytokine alterations in patients with specific types of placental lesions following SARS-CoV-2 during pregnancy. Maternal infection and inflammation can have a complex impact on early brain development and neurodevelopmental health outcomes. However, there have been very limited studies with differing conclusions addressing neurodevelopmental outcomes of infants born to mothers with SARS-CoV-2 in pregnancy. The existing literature to date utilizes methods limited by assessment of infants too early (≤12 months) and with diagnosis codes rather than direct evaluation of the child. With continued viral evolution and a generation of infants affected by the COVID-19 pandemic, it remains critical to learn if and how SARS-CoV-2 infection in pregnancy impacts childhood neurodevelopment health and risk of future dysfunction. Our central hypothesis is that pregnancy-associated SARS-CoV-2 infection and associated placental injury increases risk of adverse early childhood neurodevelopmental outcomes. We will investigate this hypothesis by utilizing our longitudinal SNIPP cohort of mother-infant pairs affected by SARS-CoV-2 infection during pregnancy (n~4000) with archived placental histopathology. We aim to characterize early childhood neurodevelopmental outcomes of infants following maternal SARS-CoV-2 during pregnancy by Aim 1(a): performing developmental assessments on infants born to the SARS-CoV-2-infected cohort along with pandemic timeframe uninfected controls; and Aim 1(b): exploring associations between neurodevelopmental abnormalities and placental injury with or without SARS-CoV-2 infection. In collaboration with Institute for Innovations in Developmental Sciences faculty, assessments will be performed using validated online parent surveys and remote video visits, focusing on both broad neurodevelopment and key domains for adaptive functioning: self-regulation and communication. A major impact of this work would be the identification of high-risk children who need close developmental monitoring. Strengths of our proposal include our large SNIPP cohort with paired biospecimens, sampling across the pandemic timeframe, and our transdisciplinary approach harnessing expertise in perinatal infection, placental pathology, and cutting-edge, pragmatic neurodevelopmental paradigms. This project uniquely poises us to address an important gap in knowledge that can impact near-term neurodevelopmental care and, through future research, lead to innovative risk stratification, mechanistic insight, and novel therapeutics to reduce harm.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15405", "attributes": { "award_id": "1F30CA287638-01A1", "title": "Characterizing DC-specific mechanisms of LNP immunogenicity to enhance LNP-based anti-tumor therapies", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Cancer Institute (NCI)" ], "program_reference_codes": [], "program_officials": [ { "id": 10305, "first_name": "YANSONG", "last_name": "Bian", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-15", "end_date": "2027-07-14", "award_amount": 42724, "principal_investigator": { "id": 32007, "first_name": "Chang Yoon", "last_name": "Moon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 625, "ror": "https://ror.org/04a9tmd77", "name": "Icahn School of Medicine at Mount Sinai", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "In the first 6 months after COVID-19 vaccine approval, 3.4 billion doses were administered globally, potentially saving 7.2 million lives. Lipid nanoparticle (LNP)-mRNA based COVID-19 vaccines have been able to induce both a strong T cell- and antibody-mediated responses against SARS-CoV-2 by triggering myeloid antigen presenting cells (APCs) such as dendritic cells (DCs), demonstrating the efficacy of LNP-mRNA technology to modulate the immune system. Partly due to the success of COVID-19 vaccines, there has been a renewed attention in engineering novel LNP formulations to better modulate the myeloid APC compartment by 1) either fine-tuning the adjuvanticity of the LNP lipid formulation or 2) improving in vivo targeting efficiency of LNPs towards myeloid APCs. Although the advancements in LNP lipid chemistry enrich our arsenal of LNP formulations suited to modulate the immune system, there hasn't been a corresponding detailed understanding of the molecular and cellular changes induced upon the uptake of LNPs in specific cell types and tissues. In fact, attempts to elucidate the innate mechanisms of LNP immunogenicity have often led to conflicting conclusions and have in turn suggested that the mechanisms of LNP immunogenicity are rather LNP formulation-dependent. The lack of consensus on the innate mechanisms of LNP immunogenicity further highlight that the immunogenicity of each LNP is a complex function of a) its lipid formulation and the nature of its payload, b) the pattern recognition receptor (PRR) profile unique to each immune subset, c) LNP targeting efficiency in each cell type and d) cell, tissue and disease context of LNP treatment. Without the parallel efforts to gain mechanistic understanding of immunogenicity of each LNP formulation, it remains difficult to rationally select LNP formulations that are tailored to a particular disease context, including cancer. In using LNPs as a cancer immunotherapeutic, my central hypothesis states that LNP lipid formulations that drive up their immunogenicity combined with an engineering strategy to increase specific targeting of DCs in vivo can synergize with immunostimulatory payloads (i.e. IL-12) to reprogram DC cell states and enhance anti-tumor immunity. In Aim 1, I will characterize the changes in DC phenotype, function and transcriptional profile upon uptake of DC-targeted LNPs in both steady state and tumoral contexts using DC-T cell co-cultures, bulk and scRNA-seq of sorted LNP transfected DCs. In Aim 2, I will engineer Clec9a targeted bi-specific antibodies to improve LNP transfection of DCs in vivo. The outcome of this project is both a mechanistic understanding of the interplay between LNPs and DCs that occurs upon LNP uptake and a novel bi-specific antibody-based strategy to increase DC targeting in vivo.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15406", "attributes": { "award_id": "1F32MD019534-01", "title": "Examining Racial Disparities in Predictive Modeling Among Survivors of Critical Illness", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Minority Health and Health Disparities (NIMHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 32008, "first_name": "ARUNDHATI", "last_name": "Gogineni", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-01", "end_date": "2026-06-30", "award_amount": 90932, "principal_investigator": { "id": 32009, "first_name": "Hiam", "last_name": "Naiditch", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 848, "ror": "", "name": "UNIVERSITY OF PITTSBURGH AT PITTSBURGH", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT SUMMARY/ABSTRACT: Survivors of critical illness often face significant challenges, such as neurocognitive disorders, physical disabilities, and respiratory limitations. Healthcare disparities by race heighten such challenges. Risk prediction tools designed to identify high-risk patients for interventions such as post-acute care clinics may exacerbate existing bias among racial and ethnic groups. Intending to address bias in prediction tools for survivors of critical illness, our team brings expertise in health services research focusing on healthcare disparities, statistical modeling, and causal inference. In previous work, we have highlighted racial differences in patients with cardiovascular disease and COVID-19 across different healthcare systems, including the Veterans Health Administration (VHA). Furthermore, we have begun exploring outcomes among survivors of critical illness including mortality and re-admission rates and developed an innovative post-ICU care model showing early indications of reducing hospital readmissions, increasing hospital-free days, and reducing mortality across diverse patient populations. As an F32 grant recipient, I will integrate and build on the expertise of my mentorship to identify and characterize racial disparities within three datasets of critical care illness survivors as defined by mortality, 90-day re-admissions, and hospital-free days (HFDs) at 90 days. In parallel, I will compare bias within two statistical models used to stratify patients by one-year mortality: (1) the Care Assessment Needs (CAN) score, a mortality risk model widely used to guide interventions among Veterans, and (2) the PREDICT score, a simplified one-year mortality risk model used at first patient contact to guide interventions such as palliative care consultation. Statistical fairness is an emerging concept geared toward reducing bias within statistical models and algorithms. To address any identified bias within our models, our team will employ novel approaches to achieve statistical fairness, including double prioritization. In addition to identifying healthcare disparities within a population of increasing care complexity, my proposal investigates statistical models as underlying contributors to healthcare disparities, aiming to rectify such inequalities through refined and equitable modeling approaches. In doing so, we propose establishing a fair care delivery framework for critical illness survivors. With close mentorship from an experienced team in healthcare disparities research, healthcare delivery, and innovative research methodologies at the University of Pittsburgh, this training plan forms a foundation for a Career Development Award and a future career as a physician-scientist.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15407", "attributes": { "award_id": "1F31CA295073-01", "title": "Development and characterization of self-amplifying RNA Lipid Nanoparticles for potent and multiplex gene expression in solid tumors", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Cancer Institute (NCI)" ], "program_reference_codes": [], "program_officials": [ { "id": 22726, "first_name": "Hana M", "last_name": "Odeh", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-01", "end_date": "2027-06-30", "award_amount": 40671, "principal_investigator": { "id": 32010, "first_name": "Arun Kannoth", "last_name": "Nambiar", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1456, "ror": "", "name": "BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Specific Aims Solid tumors account for nearly 90% of adult cancers and are challenging to eliminate. Surgery and adjuvant therapy (e.g., radiation, chemotherapy, and immunotherapy) are powerful methods for treating solid tumors. Still, they are not universally effective or curative, and would benefit significantly from some means of augmenting the tumor-killing response. Local delivery of cytotoxic, immunostimulatory, and gene therapy agents, especially in combinations, has proven very effective in promoting solid tumor clearance. Given this potential, it would be powerful to have a platform that sustainably and simultaneously delivers multiple immunostim- ulatory and gene-therapy payloads directly at the tumor, thus promoting its clearance. While current strategies, such as local drug delivery, lentivirus, and mRNA delivery methods, could generate such modifica- tions, they suffer limitations for broader use such as permanent modifications and off-target effects (lentivirus), transient gene expression (mRNA) and drug release, and limited payload. Self-amplifying RNA (saRNA) has shown great promise for prolonged and non-integrative therapeutic gene expression and coupled with lipid na- noparticles (LNPs) could serve as a viable method for local gene delivery and tumor modification. Until recently the potent early immune response triggered upon entry of saRNA into the cell has severely constraining the potency of saRNA, with standard strategies for lowering RNA immunogenicity such as incorporating the modified nucleoside N1-methyl-pseudouridine (found in all mRNA COVID vaccine) yielding non-functional saRNA. How- ever, we have recently discovered that complete substitution of saRNA with the 5 methylcytidine (5mC) drasti- cally reduces immune recognition of saRNA while preserving saRNA replication and gene expression capabili- ties, leading to elevated and prolonged transgene expression. This powerful discovery empowers the appli- cation of saRNA for other therapeutic applications and provides an opportunity to optimize these thera- pies for efficient, multiplex gene delivery. To achieve this, I propose studies for optimizing the saRNA platform by two approaches. The first approach (aim 1) will involve screening both saRNA and LNP formulation to opti- mize their gene delivery across a panel of tumor types, using our best-performing saRNA to express an innova- tive gene drive cassette that would selectively enrich the expression of a suicide gene in the tumor and overcome drug resistance. The second approach (Aim 2) will focus on maximizing transgene cargo in saRNA, screening 1) how many genes can be encoded in a single saRNA by implementing RNA sequence elements, and 2) the maximum possible length of saRNA that can be successfully delivered. This work will establish new bench- marks for RNA therapeutics, providing a platform for efficiently delivering the next generation of gene- therapies for solid tumor treatment.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15409", "attributes": { "award_id": "3U01HG010231-05S3", "title": "IGNITE Cost Extension- Year 7", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Human Genome Research Institute (NHGRI)" ], "program_reference_codes": [], "program_officials": [ { "id": 28037, "first_name": "simona", "last_name": "volpi", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-01", "end_date": "2025-06-30", "award_amount": 345120, "principal_investigator": { "id": 32012, "first_name": "Lori Ann", "last_name": "Orlando", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "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": "This cost extension for the IGNITE network was requested by NHGRI program office in order to complete the activities for the network trials GUARDD and ADOPT-PGX as well as the follow-on network activities. The delays in the trials for GUARDD and ADOPT-PGX were multifactorial and were greatly influenced by the COVID pandemic. In addition, some trial specific challenges led to delays: the length of time to develop protocols and processes, the complexity of the sIRB and reliance agreements among so many sites, procedural differences at each site, adding additional recruiting health systems mid-way, and the need to increase enrollment targets to account for adjustments to the power analysis. In this second year of the cost extension we will be completing study closeout activities, secondary analyses for papers, and continuing to participate in the network.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15410", "attributes": { "award_id": "1R01AI182177-01", "title": "Armed nanobodies as anti-infectives and anti-tumor agents", "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": 29189, "first_name": "Moriah Jovita", "last_name": "Castleman", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-19", "end_date": "2029-05-31", "award_amount": 542900, "principal_investigator": { "id": 32013, "first_name": "Hidde L.", "last_name": "Ploegh", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 798, "ror": "https://ror.org/00dvg7y05", "name": "Boston Children's Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "A nanobody that recognizes immunoglobulin light chains, conjugated to a molecular entity that recognizes a virus-infected or a cancerous cell, is an effective therapeutic: A single injection of fusion constructs comprising an anti-kappa light chain nanobody (VHHkappa) and zanamivir, a small molecule that targets influenza neuraminidase, protects mice from a lethal challenge with both A- and B-strains of influenza. In the model that established protection by VHHkappa adducts against influenza, the underlying mechanism of action involves antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), but the relative contribution of each is not known. We shall therefore use FcgR common g chain-deficient mice and C3- deficient mice to assess the relative contributions of ADCC and CDC. The generation of Fc constructs of different Ig isotypes and bearing FcR-engagement disabling mutations, similarly modified with zanamivir, will be used to complement this analysis. Having established proof-of-concept for influenza and optimized parameters for elimination of influenza virus- infected cells, we will explore nanobodies that recognize other pathogens (Ebola virus, SARS-CoV-2, HIV) in combination with VHHkappa in a series of collaborative experiments. The agents to be developed may inspire novel immunomodulatory therapeutics, to be used as a stand-alone approach, or in combination with approved drugs. The possibilities of post-exposure prophylaxis against viral infections (Ebola, SARS-CoV-2, HIV) in the absence of pre-existing immunity, deserve particular emphasis. We shall further enhance the activity of the proposed VHHkappa fusions through the generation of the corresponding drug adducts, using cytotoxic drugs such as maytansinoids as compounds that have shown clinical utility. Enveloped viruses (e.g., HIV, SARS-CoV-2) export viral proteins to the surface of the infected cell during budding. Infected cells can thus be distinguished from uninfected cells based on the surface display of viral proteins. We now extend these in vivo observations to fusions of VHHkappa with anti-checkpoint (PD-L1, CTLA-4) nanobodies. We generated maytansinoid-modified VHHkappa fusions with the anti-PD-L1 and anti-CTLA-4 VHHs. Our preliminary data show enhanced anti-tumor activity in the MC38 and B16.F10 mouse tumor models in comparison with commonly used monoclonal antibodies. However, not all such fusions (examples: fusions of VHHkappa with nanobodies that recognize Class II MHC or CD8) have shown the intended depletion efficacy in vivo. This proposal seeks to establish the parameters -including biodistribution and surface expression levels of the targeted molecules- that determine success or failure of VHHkappa fusions. The availability of VHHs that recognize human kappa light chains suggest the possibility of clinical translation of this approach.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15411", "attributes": { "award_id": "1R13AI186420-01", "title": "Mechanisms of RNA Decay", "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": 32014, "first_name": "Patricia M.", "last_name": "Strickler-Dinglasan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-16", "end_date": "2024-11-30", "award_amount": 5000, "principal_investigator": { "id": 32015, "first_name": "Olivia Selfridge", "last_name": "Rissland", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1511, "ror": "", "name": "FEDERATION OF AMER SOC FOR EXPER BIOLOGY", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "A counterbalance to RNA synthesis, RNA degradation is critical for regulating gene expression. The understanding that RNA degradation is critical for gene expression traces back to 1959 when Pardee, Jacob and Monod demonstrated in a historical paper that there had to be an unstable intermediate directing protein synthesis. Groundbreaking research over the past decades led to the identification of a variety of specific and tightly regulated RNA decay pathways and biochemical characterization of the enzymes involved in them, both in eukaryotic and prokaryotic organisms. The clinical applications in the post-transcriptional regulation/RNA field are now being realized with the initial development of Nusinersen/Spinraza® to successfully treat Spinal Muscular Atrophy and the more recent description of Milasin® to treat a single patient through a personalized RNA therapy. Of course, in 2020, RNA burst onto the global stage in a way we could not have predicted with the COVID-19 RNA virus impacting life as we know it across the globe. Who would or could have guessed that RNA could also represent a potential path back to a new normal via the rapid development and deployment of the first mRNA vaccines. All these examples highlight why the FASEB meeting on ‘Mechanisms of RNA Decay’ is timely. This meeting has developed into a unique conference that brings together the leading experts in RNA decay in humans and other metazoan animals, plants, fungi, viruses, and bacteria. This meeting is the 13th is a series of FASEB meetings on this topic where there is a long tradition of sharing key discoveries, building collaborations, and contributing to career development for junior scientists in the field. This meeting, held August 18–22, 2024 in Lisbon, Portugal, is co-organized by three leaders in the RNA decay field, Dr. Olivia Rissland from University of Colorado School of Medicine, USA, Dr. Alicia Bicknell from Moderna Therapeutics, and Dr. Oliver Muhlemann from University of Bern, Switzerland. We propose three specific aims for this meeting: 1) Bringing together the international community working on RNA degradation and providing an intellectually stimulating and mutually supportive forum for the presentation and discussion of the latest advances in the field; 2) Providing an inclusive and friendly environment for establishing collaborations between researchers studying RNA degradation with different approaches and in different organisms; and 3) Encouraging productive interactions between a diverse group of both junior scientists and world leaders in the RNA degradation field. In keeping with the meeting goals, the organizers are committed to inclusive excellence: Among the 28 invited speakers, there are 13 women (46%) and a well-balanced gender ratio will be ensured among the 25 additional oral presentations that will be selected from the submitted abstracts. Also, among the 10 session chairs, six are women. We are excited to include trainee co-chairs, who will be selected from the short-talk presenters. The long-term goal is to continue a successful meeting series that addresses modern and timely topics in RNA decay and strengthens the interactions within a diverse and inclusive community of collaborative scientists and colleagues.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15412", "attributes": { "award_id": "1R21AI185841-01", "title": "Optimization of novel inhibitors of mycolic acid synthesis as TB drug candidates.", "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": 32016, "first_name": "Jim P.", "last_name": "Boyce", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-17", "end_date": "2026-06-30", "award_amount": 237288, "principal_investigator": { "id": 32017, "first_name": "Kyle H", "last_name": "Rohde", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32018, "first_name": "Jennifer Marie", "last_name": "Schomaker", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1475, "ror": "https://ror.org/036nfer12", "name": "University of Central Florida", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is responsible for staggering levels of morbidity and mortality, with ~1.7 million deaths and ~10 million new cases each year. The current TB regimens for drug susceptible strains, entailing multidrug cocktails for ≥4 months, leave much to be desired. The cost and logistics of administering standard of care regimens over many months and the inability of many patients to tolerate the debilitating side effects further complicate the clinical control of TB. The lingering negative impacts of the COVID pandemic on TB control efforts and increasing challenge of multidrug-resistant Mtb strains, which have only a ~50% treatment success rate, further highlight the urgent need for better antibiotics to tackle this problem. Even our definition of what “better” means has shifted based on recent appreciation of the heterogeneity of mycobacteria subpopulations that must be eradicated, including replicating and non-replicating bacilli residing both extracellularly and within host cells in diverse microenvironments. Thus, effective drug combinations must not only access mycobacteria within different niches and layers of granulomas but also be able to kill Mtb in many distinct metabolic states while minimizing the emergence of resistance. In order to meet this urgent need for game-changing new treatment options for TB, it is imperative to maintain a robust pipeline of new anti-TB drug candidates with the potential to meet these demanding performance criteria. This project seeks to address this need by building on our recent discovery of a first-in-class series of compounds that kill Mtb via inhibition of a well- validated but underexploited target enzyme essential for cell wall synthesis. Thus far, we have demonstrated sub-micromolar potency, enhanced potency against Mtb within macrophages, high specificity for Mtb, and high selectivity over mammalian cells. We have strong evidence that these compounds act via inhibition of an essential enzyme involved in mycolic acid biosynthesis for which there are currently no viable preclinical candidates. The first major goal of this project is hit-to-lead optimization and elucidation of structure-activity relationships, using whole cell potency and ADME/PK properties as key drivers of compound prioritization. Secondly, we will employ orthogonal approaches to further validate the target and ensure that optimized lead compounds remain on-target. Successful completion of this project will set the stage for subsequent lead optimization and in vivo efficacy studies of a promising new class of cell-wall targeting TB antibiotics.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15413", "attributes": { "award_id": "1UG3AI181797-01", "title": "Coordinating and Data Sharing Center - R&D of Vaccines and Antibodies for Pandemic Preparedness (ReVAMPP)", "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": 32019, "first_name": "ANNE ELIZABETH MAYER", "last_name": "Bridwell", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-16", "end_date": "2027-06-30", "award_amount": 7994888, "principal_investigator": { "id": 32020, "first_name": "Sean Thomas", "last_name": "Hanlon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32021, "first_name": "Gregory D", "last_name": "Sempowski", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 809, "ror": "", "name": "RESEARCH TRIANGLE INSTITUTE", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "0BPROJECT SUMMARY/ABSTRACT The global pandemic caused by SARS-CoV-2 highlighted the continual threat of emerging and re-emerging pandemic-potential pathogens and the critical value of coordinated multidisciplinary basic and translational research for pandemic preparedness. There is an urgent need for an integrated collaborative effort to build a robust basic research and translational science portfolio for preparedness against high-risk viral families including Paramyxoviridae, Picornaviridae, and Bunyavirales. The National Institute of Allergy and Infectious Diseases (NIAID) is supporting the development of the Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness (ReVAMPP) Network to fill this critical gap. The overall goal of this new collaborative Network, consisting of a Coordinating and Data Sharing Center (CDSC) and six to eight Research Centers, is to collaboratively produce generalizable knowledge that enables a rapid response when previously understudied or unknown pathogens emerge. RTI International’s well-established track record implementing large-scale domestic and international coordinating and data management centers, including in the emerging infectious disease ecosystem, makes us well qualified to develop and provide Network governance, communications, and data sharing and analysis as the ReVAMPP CDSC. The overall goal of the RTI-based CDSC is to establish and maintain an integrated Network to accelerate discovery and dissemination of novel vaccine and monoclonal antibody strategies to prepare for the next pandemic outbreak. To accomplish this goal, RTI proposes a CDSC organizational structure, consisting of two interconnected teams under mPIs and a Project Director—an Administration and Leadership Team, and a Data Management and Analysis Team. This structure leverages RTI multidisciplinary experts and will provide ReVAMPP Centers, NIAID, and stakeholders centralized administrative, communication, and operational support for Network-wide activities, while also establishing data sharing and analysis standards and platforms. The Specific Aims of the RTI-based CDSC align with these two teams and will use both established and novel innovative approaches and technologies to (Aim 1) coordinate preparatory vaccine and antibody strategy research by establishing and maintaining ReVAMPP Network governance, administration, and communication; and (Aim 2) accelerate transparent collaborative vaccine and antibody strategy research by developing and maintaining a secure ReVAMPP Network Private Portal that includes centralized resource, data sharing, and reporting systems. This independent, but integrated team of administrators, communicators, and data science experts embedded within the ReVAMPP Network as the CDSC, will coordinate, facilitate, and empower Network investigators and NIAID to proactively prepare to rapidly share information with key stakeholders across the globe when new viral pandemic/outbreaks occur.", "keywords": [], "approved": true } } ], "meta": { "pagination": { "page": 1391, "pages": 1424, "count": 14236 } } }