Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1383&sort=program_officials
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=program_officials", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1397&sort=program_officials", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=program_officials", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1382&sort=program_officials" }, "data": [ { "type": "Grant", "id": "14869", "attributes": { "award_id": "1R01EB035498-01A1", "title": "A universal intranasal nanoengineered therapy against airborne RNA viruses", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Biomedical Imaging and Bioengineering (NIBIB)" ], "program_reference_codes": [], "program_officials": [ { "id": 31558, "first_name": "JERMONT", "last_name": "Chen", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-03", "end_date": "2028-04-30", "award_amount": 664392, "principal_investigator": { "id": 31559, "first_name": "Vinay Subhash", "last_name": "Mahajan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 891, "ror": "https://ror.org/04b6nzv94", "name": "Brigham and Women's Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "The past two decades have witnessed several air-borne viruses (SARS-CoV1, MERS, SARS- CoV2) that led to significant mortality. There is always a lag time before a vaccine is introduced. This lag creates an urgent need for a universal antiviral therapy that can be deployed rapidly as a prophylactic measure. Here, we propose to address this gap by engineering a novel intranasal- delivered nanoparticle that exerts an universal antiviral effect by activating a unique evolution- encoded innate immune state in nasal epithelial cells to provide early protection. There is a strong rationale for targeting nasal epithelium for an antiviral prophylaxis for air-borne viruses: (1) Nasal epithelium is the most common portal of entry of these pathogens; (2) The nasal cavity and nasopharynx contain some of the highest viral loads; and (3) Neutralizing the virus in the nasal epithelium has been shown to not only decrease viral load in both the nasal cavity and in distant sites, but potentially reduce transmission from asymptomatic individuals. While these studies validate nasal delivery as an ideal route of administration for viral prophylaxis, an effective universal antiviral therapy remains an unmet need. We hypothesize that activating an evolutionary conserved antiviral mechanism, i.e. the induction of IFN-Induced proteins with tetratricopeptide repeats 1 (IFIT1), can emerge as an effective universal prophylaxis against airborne viruses. This can be achieved by inhibiting CMTR2, a novel target, in the nasal epithelium. We will: (Aim 1) Engineer antiViral Response-Activating Nanoparticles (V-RANs) for intranasal delivery and test for inhibition of CMTR2 and induction of IFIT1; (Aim 2) Evaluate the antiviral efficacy and safety of V- RANs in mouse models of severe SARS coronavirus or pandemic flu infections; and in (Aim 3) Elucidate the molecular mechanism of V-RAN-induced antiviral response. Published reports and our preliminary results demonstrate the feasibility of this project. This study can lead to new insights into intranasal nanodelivery, and a novel antiviral prophylaxis that can shift the paradigm for early interventions in future pandemics.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14871", "attributes": { "award_id": "1F32HL168826-01A1", "title": "Low-energy cooling strategies to reduce the thermal, cardiovascular, and renal consequences of heat waves in the elderly.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 31561, "first_name": "Wayne C.", "last_name": "Wang", "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": 69080, "principal_investigator": { "id": 31562, "first_name": "Zachary John", "last_name": "McKenna", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1215, "ror": "", "name": "UT SOUTHWESTERN MEDICAL CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Heat waves cause a disproportionate number of deaths in the elderly relative to any other age group. Most of the hospitalizations and deaths in this population during heat waves are due to cardiovascular and renal complications linked to elevated thermal strain, and not directly due to hyperthermia per-se. Indoor cooling with an air conditioner remains the most effective strategy to prevent the deleterious health effects of heat waves. However, approximately 1 in 8 Americans do not have in-home air conditioners, and the rising household energy costs potentially makes air conditioning unaffordable for lower-income individuals. Also, power outages and industry/government-imposed rolling blackouts, along with COVID-19 related closures of public spaces, threaten region-wide access to air conditioning at times when it is most needed. Thus, there is a clear need to identify non-air conditioning dependent cooling modalities to attenuate excessive elevations in core body temperature and associated cardiovascular and renal stress in the elderly during heat wave conditions. The broad goal of this project is to test the efficacy of low-energy cooling strategies directed at mitigating the adverse thermal, cardiovascular, and potential renal consequences of heat wave exposure in the elderly. Aim 1 will test the hypothesis that skin wetting is an effective cooling modality to attenuate elevations in core body temperature and accompanying cardiovascular stress during heat waves in the elderly, while fan use may be detrimental depending on air temperatures and whether skin wetting is also employed. Aim 2 will determine if recognized impairments in thermoregulatory capacity and aging-related reductions in kidney function in the elderly will culminate in increased renal stress during heat wave exposures. The expected outcomes from this work will have a direct positive impact on the elderly by evaluating the efficacy of practical, low-energy cooling strategies that have the potential to save lives during heat waves. Further, we will provide critical information that comprehensively characterizes the extent of renal stress during simulated heat waves in elderly individuals. This research directly supports the mission of NIH in that we will uncover mechanistic physiological findings from human participants with the goal of translating these findings to guide individuals, caregivers, and communities on effective approaches to reduce heat related illness/injury. To ensure that this study was designed to maximize clinical relevance and my scientific training, I assembled a strong interdisciplinary clinical research/mentoring team consisting of expert integrative physiologists, physician-scientists, and a biostatistician. My primary goals during this fellowship are to complete the proposed project, master several technical skills (e.g., cardiac echocardiography, assessment of renal function/injury, etc.), improve my ability to obtain future extramural research funding, and publish research findings in peer-reviewed medical and physiology journals.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14873", "attributes": { "award_id": "1U18HS029937-01", "title": "Supporting Patients Recovering from COVID-19 (SPaRC)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Agency for Healthcare Research and Quality (AHRQ)" ], "program_reference_codes": [], "program_officials": [ { "id": 31564, "first_name": "Latrice", "last_name": "Vinson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-01", "end_date": "2029-06-30", "award_amount": 1000000, "principal_investigator": { "id": 31565, "first_name": "Ann Marie", "last_name": "Parker", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 344, "ror": "https://ror.org/00za53h95", "name": "Johns Hopkins University", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Project Summary: Long COVID impacts 10-30% of people after a SARS-CoV-2 infection, with potentially devastating long-term impact on quality of life. Moreover, Long COVID disproportionately affects minority, rural, older, and other at-risk populations. Multidisciplinary Long COVID clinics provide clinical care and offer infrastructure for evaluating promising interventions to improve Long COVID outcomes. The Johns Hopkins Post-Acute COVID-19 Team (JH PACT) is among the country's first and largest Long COVID programs. Via this AHRQ U18 proposal, JH PACT proposes the following Aims: (1) To deliver a comprehensive, multidisciplinary program (Supporting Patients Recovering from COVID, “SPaRC”) to patients with Long COVID, with an expanded focus on underserved populations. The SPaRC program will expand on the existing expertise of the JH PACT multidisciplinary Long COVID outpatient program to increase capacity and decrease wait times, with expanded services to underserved patient populations, including older adult, minority race/ethnicity, socioeconomically disadvantaged, and geographically distant and rural populations via enhanced partnerships with key existing organizations (e.g., Medicine for Greater Good, Center for Clinical Global Health Education). (2) To iteratively evaluate and refine the SPaRC Long COVID program to increase access and improve patient-centered, evidence-based care. The SPaRC program will be evaluated and iteratively refined in quarterly cycles via mixed methods evaluation (via patient data from electronic medical records and semi-structured qualitative interviews of patients/caregivers and staff/clinicians) to inform implementation strategies based on the “Expert Recommendations for Implementing Change” (ERIC) framework within a learning health system. In each review cycle, the implementation team and key SPaRC internal and external stakeholders will evaluate the program and outcomes and select goals for refinement and advancement for the next quarterly review cycle. An external Stakeholder Advisory Council, led by an independent Chair, will provide ongoing feedback via quarterly meetings throughout the project. (3) Partner with regional Long COVID stakeholders, including primary care providers (PCPs), to create and expand access to comprehensive, patient-centered, coordinated Long COVID care across the mid-Atlantic region. We will build a multi-disciplinary Long COVID provider-to-provider e-consult service, customized educational curriculum (delivered via both live and on-demand electronic formats), and continuing education toolkit for PCPs, in conjunction with key stakeholders (e.g., patients, caregivers, community leaders, and PCPs). JH PACT and the SPaRC Team include internationally-recognized experts in Long COVID care, patient outcomes assessment, implementation science, stakeholder/community engagement, and primary care education. JH PACT is ideally positioned to create a Long COVID Center of Excellence, leveraging the outstanding expertise available via Johns Hopkins Medicine, and to optimally engage with the AHRQ Learning Community.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15448", "attributes": { "award_id": "5U18HS029911-02", "title": "Advancing Long COVID Care in our Community through Access, Equity, and Collaboration", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Agency for Healthcare Research and Quality (AHRQ)" ], "program_reference_codes": [], "program_officials": [ { "id": 31564, "first_name": "Latrice", "last_name": "Vinson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-30", "end_date": "2028-09-29", "award_amount": 931222, "principal_investigator": { "id": 28180, "first_name": "Abby Ling-Lee", "last_name": "Cheng", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 28181, "first_name": "Jonas", "last_name": "Marschall", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 28182, "first_name": "Amy", "last_name": "McQueen", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 827, "ror": "", "name": "WASHINGTON UNIVERSITY", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "Long COVID manifests differently for each person and can contribute to disabling, life-changing symptoms such as extreme fatigue, cognitive dysfunction, breathing difficulty, and autonomic dysfunction in people across the age spectrum, including in people who were previously healthy and in people who had minimal or no symptoms associated with acute COVID-19 infection. Multidisciplinary Long COVID clinics were a mainstay of patient support during the initial phases of the COVID-19 pandemic, but as the pandemic is shifting to a new phase, care models must also evolve in order to meet the complex medical, rehabilitative, and social needs of the continually growing number of people who are affected by Long COVID. The purpose of this project is to transform an existing, university-based Long COVID clinic into a broader Long COVID community network in order to expand equitable access to care, improve the patient care experience, and support primary care practitioners. This project will invest in two particularly underserved populations: 1) the Black community in St. Louis, Missouri, which is a historically mistreated population who continues to be marginalized by previously sanctioned segregation practices; and 2) rural communities across Missouri. Aim 1 is to expand equitable access to Long COVID care by: 1) building clinical capacity, and 2) removing structural barriers to care. This will be accomplished by: 1) hiring additional clinicians for the Long COVID Clinic in order to reduce wait times; and 2) removing patient requirements for clinic evaluation that disproportionately affect underserved populations. Aim 2 is to improve the Long COVID care experience by: 1) streamlining care that crosses multiple disciplines and physical care sites, and 2) supporting patients’ social needs. This will be accomplished by: 1) supporting a clinical case manager to directly assist patients with coordinating medical care and connecting with community resources, and 2) iteratively assessing and addressing referral challenges between clinics. Aim 3 is to support primary care teams as they care for patients with Long COVID by co-creating: 1) educational resources for PCPs, and 2) streamlined communication and referral pathways between PCPs and specialty clinicians. This will be accomplished by engaging multiple key stakeholders to: 1) develop multi- modality educational materials related to Long COVID patient assessment and management; 2) disseminate materials via culturally and logistically preferred approaches (including via established, trusted community intermediaries and via an established ECHO (Enhanced for Community Healthcare Outcomes) virtual educational infrastructure); and 3) refine existing handoff processes to minimize the administrative workload on PCP teams and facilitate their ability to meet patients’ needs. Continuous stakeholder input, comprehensive data tracking, and iterative needs assessments using mixed methods approaches will facilitate ongoing project evaluation and adaptation in order to respond to the community’s evolving needs.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15475", "attributes": { "award_id": "5U18HS029943-02", "title": "Novel Statewide Response to Post-COVID Care Delivery", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Agency for Healthcare Research and Quality (AHRQ)" ], "program_reference_codes": [], "program_officials": [ { "id": 31564, "first_name": "Latrice", "last_name": "Vinson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-30", "end_date": "2028-09-29", "award_amount": 976981, "principal_investigator": { "id": 28235, "first_name": "Sarah E", "last_name": "Jolley", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 22611, "first_name": "DONALD E", "last_name": "NEASE", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 784, "ror": "https://ror.org/02hh7en24", "name": "University of Colorado Denver", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "Long COVID is an important public health threat impacting millions of individuals including 600,000 Coloradans. Current Long COVID care is highly fragmented, variable in nature, and in constant evolution. Creating a novel approach to practice support with continued education and streamlining care for high Long COVID will improve care integration and patient experience. We will implement the Colorado Multidisciplinary Translation Network (CO-MTN) comprised of integrated, multidisciplinary Long COVID care clinics and primary care clinics working together in a tiered care delivery pathway. CO-MTN creates a bidirectional translational care network for integrating expertise, education, referrals, and care between MDCs, PCPs and teams, and their patients. CO-MTN includes 1) the State of Colorado-supported Long COVID Community of Practice comprised of three geographically distributed MDCs, 2) a state-wide practice-based research network representing 280 primary care practices, known as the State Networks of Colorado Ambulatory Practices & Partners, and 3) a proven tele-education system used to provide health care practitioners specialty training, Extension for Community Healthcare Outcomes. CO-MTN includes implementation strategies to support the tiered care pathway including training and learning communities to support PCPs with improved knowledge and capacity and provide exceptional care for Colorado Long COVID patients, and practice facilitation to effectively implement the PCP care in their practice and coordinate with the MDCs. CO-MTN will help Long COVID patients in Colorado and have the potential for scaling to other states. To guide implementation and evaluation, we will utilize the Exploration, Preparation, Implementation and Sustainment dissemination and implementation framework. We will measure sustainment as continued involvement in the network during the final six months of the project period. Using qualitative, quantitative, and mixed methods, we will evaluate the Reach and Effectiveness for patients, and the Adoption, Implementation and Maintenance of the implementation strategies using the RE-AIM framework based on the following aims: Aim 1: Implement an integrated, tiered care delivery pathway with facilitated implementation support via CO-MTN and measure its effect on 1) Reach of Long COVID care to Colorado patients, specifically those described as underserved, and 2) Effectiveness on reducing Long COVID symptom burden and severity for patients engaged. Aim 2: Determine the effect of CO-MTN on 1) Adoption of the CO-MTN tiered care delivery model by primary care clinics and PCPs within these clinics, 2) Implementation of the tiered care pathway, and 3) Maintenance of the tiered care pathway key components past the active project period. Our team is comprised of national experts in Long COIVD care, practice-based research, and implementation science. Together, our multidisciplinary team will partner through CO-MTN structures and support to deliver high quality Long COVID care.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14880", "attributes": { "award_id": "1R13AI186265-01", "title": "Positive Strand RNA Viruses: Interdisciplinary Advances in Virology, Pathogenesis, Immunology, and Technology Development", "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": 31573, "first_name": "ADELINA EWURA-ABENA", "last_name": "Bartels", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-11", "end_date": "2025-06-30", "award_amount": 4000, "principal_investigator": { "id": 27075, "first_name": "TERRY L.", "last_name": "SHEPPARD", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1633, "ror": "", "name": "KEYSTONE SYMPOSIA", "address": "", "city": "", "state": "CO", "zip": "", "country": "United States", "approved": true }, "abstract": "Support is requested for a Keystone Symposia conference entitled Positive Strand RNA Viruses: Interdisciplinary Advances in Virology, Pathogenesis, Immunology, and Technology Development, organized by Drs. Kizzmekia Corbett-Helaire, William Klimstra and Jolanda Smit. The conference will be held in Killarney, Ireland from October 21–25, 2024. Positive-strand RNA viruses have proven to be an impactful global health priority that is experiencing a unique moment, which is fueled by the momentum of the COVID-19 pandemic and driven by the influx of new knowledge and technologies. Successful scientific breakthroughs in this area are the result of advances in basic virological understanding and molecular genetics, merged with other fields such as human immunology, structural biology, and vaccine development. Together, these alignments have opened new multidisciplinary frontiers and created exciting opportunities for virology research. This conference will take a tour of new knowledge in positive-strand RNA virology starting with virus-host interactions and ending with technological and clinical development. The interdisciplinary nature of the conference will provide novel insights across virology, viral immunity, vaccinology and more. In addition, the conference will feature a diverse array of positive-strand RNA viruses, including understudied viruses, revealing common themes and distinctions that might be leveraged for clinical utility. Throughout the conference, new and emerging young investigators will be highlighted alongside field leaders to bring forth new ideas and perspectives for discussion that will advance the field in innovative directions.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14912", "attributes": { "award_id": "1R35GM154852-01", "title": "Multidimensional approaches to understand and improve RNA therapeutic design and delivery", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 31602, "first_name": "Sailaja", "last_name": "Koduri", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-06-10", "end_date": "2029-04-30", "award_amount": 371606, "principal_investigator": { "id": 31603, "first_name": "Connie", "last_name": "Wu", "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": "PROJECT SUMMARY: RNA therapeutics are experiencing a renaissance with the clinical successes of the COVID-19 messenger RNA (mRNA) vaccines. In parallel, nanomaterials have emerged as highly promising vehicles for RNA delivery. However, despite considerable scientific advances in nanoparticle therapeutics over the last several decades, few nanoparticle-based RNA therapeutics have been clinically approved. As the RNA therapeutics landscape expands, there remain key understanding gaps that must be addressed to inform the rational design of RNA therapeutic systems across molecular, cellular, and organismal levels and enable broad clinical translation: (1) how RNA cargo parameters, carrier properties, and their combinations govern functional in vivo RNA delivery; (2) how the biological environment of the host alters RNA nanocarriers and their in vivo functionalities; and (3) in turn, how RNA therapeutic systems modify the host. Further exacerbating these knowledge gaps is a lack of high-sensitivity, high-throughput tools for interrogation of functional in vivo RNA delivery, nanoparticle-biomolecule interactions, and the host response. The proposed program will adopt multi- pronged strategies to address these challenges, by integrating our complementary expertise in ultrasensitive biomolecule detection, RNA engineering, and nanoparticle drug delivery. Using mRNA as a representative RNA drug, we seek to elucidate design rules for both RNA nanocarrier and cargo for functional RNA delivery. Leveraging our technology for multiplexed single-molecule detection of low abundance biomolecules, we will pursue orthogonal focus areas: (1) develop and apply an ultrasensitive screening platform for pooled in vivo analysis of mRNA therapeutic systems, to identify RNA cargo and carrier determinants of functional mRNA delivery; (2) understand and predict the host response to RNA therapeutic systems via high-multiplex single- molecule protein detection; and (3) probe the biomolecular interactions of nanocarriers and their effects on in vivo functionality via high-throughput, high-resolution profiling of biomolecule adsorption. These three independent yet synergistic directions align well with NIGMS mission objectives in the application of innovative physical methodologies and quantitative approaches to establish foundations for disease treatment. If successful, this program will build an integrated understanding of RNA therapeutic system design rules and host factors that govern RNA delivery and individual response. The ultrasensitive profiling tools developed in this work will be of broad utility across diverse RNA therapeutic systems and disease applications.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15057", "attributes": { "award_id": "5R44GM149095-02", "title": "Use of Time Series Biomarker and Clinical Data to Construct a Time Trajectory Host Response Map", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 31602, "first_name": "Sailaja", "last_name": "Koduri", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-06-01", "end_date": "2025-05-31", "award_amount": 1272176, "principal_investigator": { "id": 12385, "first_name": "Bobby", "last_name": "Reddy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1193, "ror": "", "name": "Prenosis, Inc.", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 2017, "ror": "", "name": "PRENOSIS, INC.", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "Principal Investigator/Program Director (Last, first, middle): Reddy, Jr., Bobby Project Summary: Sepsis is an incompletely understood clinical syndrome characterized by a dysregulated host response to infection. In partnership with 8 U.S. hospitals, Prenosis amassed one of the world’s largest datasets and biobanks that combines biomarker and clinical data for patients suspected of infection, housing over 70,000 plasma or serum samples from over 14,000 patients. We also curated a dataset of dense time-series data from each patient’s Electronic Medical Record (EMR), including demographics, vitals, lab results, interventions, outcomes, and many other parameters. To commercialize insights from these data, Prenosis built ImmunixTM, an FHR/HL7 compatible software platform for clinical deployment of diagnostics and clinical decision support tools. Under a previously awarded NIGMS grant (1R44GM139529), Prenosis built a testing pipeline to measure 40 critical protein biomarkers from biobanked samples. To date, we measured these biomarkers on only the initial sample per patient for 6,000 patients and combined these data with EMR clinical parameters to construct 8 endotypes of sepsis. The identification and classification of endotypes—groupings of patients with similar biologic and clinical features—is increasingly becoming recognized as a valuable methodologic approach to assessing patients with sepsis. To complete work for the existing grant, Prenosis will measure the baseline sample for additional patients to total about 10,000 patients to refine and validate the endotypes. In this project, Prenosis proposes to add a critical new dimension to the data by assaying and analyzing longitudinal, time-series biomarker data. We will leverage our pipeline to measure the 40 core biomarkers from 9,000 follow-up samples from ~3,400 patients that we have already collected and stored in the biobank. We will assess the additional value of longitudinal time-series biomarker measurements and clinical data. Initial feasibility data from over 1,000 measured samples demonstrates that longitudinal data provide additional powerful new biologic and prognostic insights. Analytics built upon these data have the potential to improve diagnostic and drug development products for sepsis and COVID. The overall hypothesis of this project is that longitudinal biomarkers will add a valuable biologic and prognostic dimension to endotypes for sepsis; and these longitudinal endotypes will better classify patients who may have a heterogeneous response to sepsis therapies.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15182", "attributes": { "award_id": "1R01GM155729-01", "title": "Zwitterionic polyethylene glycol for therapeutic delivery", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 31602, "first_name": "Sailaja", "last_name": "Koduri", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-09-05", "end_date": "2026-06-30", "award_amount": 318457, "principal_investigator": { "id": 27922, "first_name": "Hao", "last_name": "Cheng", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 377, "ror": "https://ror.org/04bdffz58", "name": "Drexel University", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Biologic drugs and nanomedicines with conjugated polyethylene glycol (PEG) show extended circulation in the blood, increasing therapeutic efficacy. The U.S. FDA has approved more than 30 PEGylated biologics, including proteins, nucleotides, and peptides, and a few PEGylated nanomedicines, for example COVID-19 mRNA vaccines. Attached PEG chains increase the hydrodynamic radiuses of these therapeutics to reduce their renal clearance during blood circulation. More importantly, PEG conceals therapeutics from immune cells by repelling plasma proteins, rendering therapeutics stealth behavior. The adsorption of a few types of plasma proteins onto therapeutics can lead to the removal of therapeutics by immune cells. PEG chains are hydrophilic and flexible. They can repel plasma proteins through a thermodynamic-driven entropic repulsion. Despite the unique advantage, the application of PEGylated therapeutics is limited by the presence of anti-PEG antibodies (aPEG Abs). These antibodies not only accelerate the clearance of PEGylated therapeutics and attenuate their efficacies but may also cause severe side effects. Varied percentages of populations were found to have pre- existing aPEG Abs in different studies, with the percentage as high as 40%. The high prevalence is likely due to the broad use of PEG in cosmetic and healthcare products. To further improve the pharmacokinetics of therapeutics and circumvent the problem of aPEG Abs, researchers have strived to find PEG alternatives. Among these alternative polymers, zwitterionic polymers have attracted the most attention. In contrast to PEG, zwitterionic polymers repel protein adsorption by forming a hydration layer around the polymers. We hypothesize that zwitterionic PEG (ZPEG) that combines the advantageous characteristics of both PEG and conventional zwitterionic polymers will be superior to them in extending the circulation of therapeutics and minimize the generation of anti-ZPEG antibodies. To develop a ZPEG to replace PEG for therapeutic delivery, we propose the following research plans: 1) synthesize and characterize ZPEG with different chemical structures and reveal the mechanism of enhanced blood circulation of ZPEG-modified proteins; 2) investigate the immunogenicity of ZPEG; 3) investigate the pharmacokinetics and immune responses of nanoparticles covered with ZPEG. Because of the broad application of PEG, an excellent PEG replacement will generate tremendous societal impact. This project will pave the way to replace PEG with ZPEG in therapeutic delivery for minimized side effects and consistent efficacy.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15627", "attributes": { "award_id": "1R43GM157920-01", "title": "Three-Dimensional Spatio-Temporal Control of Lipid Nanoparticle Manufacturing for Improved Nucleic Acid Delivery", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 31602, "first_name": "Sailaja", "last_name": "Koduri", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-01-01", "end_date": "2025-06-30", "award_amount": 306873, "principal_investigator": { "id": 32127, "first_name": "Po-Lun", "last_name": "Feng", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2551, "ror": "", "name": "OSEM FLUIDICS INC", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic has established the importance of nucleic acid-based lipid nanoparticles (LNPs) for the future of global health. The benefits of lipid nanoparticles are multifaceted as they protect sensitive pharmaceutical payloads from enzymatic degradation and allow for the modification of solubility, release kinetics, and bioavailability. While chemical formulation of LNPs has been widely explored, the effects of manufacturing—specifically microfluidics processing—are not currently well-understood. This knowledge gap presents challenges in the production of intricate nanoparticle structures, which require specialized microfluidic systems that produce well-defined and reproducible flow configurations. The proposed research focuses on developing 3D-printed channel architectures to precisely control LNP structure and properties to enhance transfection efficiency without modifying their chemical composition. Aim 1 involves designing, simulating, and testing various 3D channel architectures to manipulate flow conditions and tailor LNP properties. Aim 2 focuses on structural determination via SAXS and CryoTEM, and assesses the impact of LNP structures on mRNA transfection efficiency through in vitro transfection studies. Aim 3 will demonstrate the therapeutic- and disease-agnostic design workflow by robustly encapsulating siRNA and pDNA. This project aims to overcome the limitations of current LNP manufacturing methods which are constrained by fixed geometries and limited control over LNP assembly processes. Development of our enabling technology will offer an additional process parameter - channel architecture, for tuning LNP properties and structure in a rapid and customizable manner that is broadly applicable.", "keywords": [ "3-Dimensional", "3D Print", "Acceleration", "Address", "Affect", "Architecture", "Biological Availability", "COVID-19", "COVID-19 pandemic", "COVID-19 vaccine", "Characteristics", "Chemicals", "Chemistry", "Cholesterol", "Complex", "Development", "Devices", "Disease", "Encapsulated", "Formulation", "Foundations", "Future", "Gene Delivery", "Gene Expression", "Geometry", "Image", "In Vitro", "Kinetics", "Knowledge", "Lipids", "Liquid substance", "Messenger RNA", "Methods", "Microfabrication", "Microfluidic Microchips", "Microfluidics", "Modality", "Modification", "Nucleic Acids", "Outcome", "Pharmacologic Substance", "Phase", "Process", "Production", "Property", "Reproducibility", "Research", "Research Personnel", "Roentgen Rays", "Route", "SARS-CoV-2 spike protein", "Series", "Small Interfering RNA", "Solubility", "Structure", "System", "Technology", "Testing", "Therapeutic", "Time", "Transfection", "United States National Institutes of Health", "clinically relevant", "cost", "design", "experimental study", "fabrication", "fluid flow", "global health", "improved", "in vivo", "innovation", "interest", "lipid nanoparticle", "mRNA lipid nano particle vaccine", "manufacture", "manufacturing systems", "millimeter", "nanoparticle", "novel", "novel therapeutics", "nucleic acid delivery", "nucleic acid structure", "nucleic acid-based therapeutics", "operation", "particle", "pre-clinical", "prevent", "spatiotemporal", "therapeutic development", "tool" ], "approved": true } } ], "meta": { "pagination": { "page": 1383, "pages": 1397, "count": 13961 } } }