Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=2&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=1392&sort=other_investigators", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=3&sort=other_investigators", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=other_investigators" }, "data": [ { "type": "Grant", "id": "14977", "attributes": { "award_id": "5T32TR004537-02", "title": "CTSA Predoctoral T32 at Albert Einstein College of Medicine", "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": 24807, "first_name": "ANTHONY THOMAS", "last_name": "Dibello", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-06", "end_date": "2028-06-30", "award_amount": 234928, "principal_investigator": { "id": 27786, "first_name": "H Dean", "last_name": "Hosgood", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 741, "ror": "https://ror.org/05cf8a891", "name": "Albert Einstein College of Medicine", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "This application seeks to continue a longstanding CTSA-supported predoctoral program, the PhD in Clinical Investigation (PCI) at the Albert Einstein College of Medicine (Einstein). PCI combines specialized training to prepare biomedical scientists to understand and appreciate the methodologies of clinical and population science, to practice team science as both leaders and members of research teams, and to advance the discipline of translational science. PCI leverages Einstein's longstanding success in fundamental laboratory- based research. PCI's unique integration with our master's degree-granting Clinical Research Training Program (CRTP), along with our requirement that each student's research and mentoring team must “bridge a translational divide,” fosters multidisciplinary team science while teaching the methodologies to overcome barriers plaguing translational research. PCI has (1) conferred 18 PhDs, (2) 12 current trainees, (3) sustained enrollment of trainees from historically marginalized communities (HMCs), and (4) a dramatic increase in inquiries and applicants. Einstein is located in the Bronx, NY, the most diverse and poorest urban county in the United States, whose catchment area experiences racial and ethnic disparities in health outcomes related to cancer, cardiovascular disease, and infectious diseases. Since much of our trainees' research involves patient data and samples from our catchment area, PCI has essentially been training trainees to conduct clinical and translational science (TS) research that meaningfully contributes to our understanding and mitigation of disparities that disproportionately affect HMCs. Building from our program's success and increased demand, we seek to evolve PCI during the next funding period with formalized emphasis on integrating health equity (HE) into our training and ensuring program sustainability. We will integrate health disparities research with a focus on overcoming barriers to HE into our training though collaboration with the Community and Stakeholder Engagement Research Module of our companion CTSA UM1. We will improve training of the next generation of trainees, who have been unfavorably affected by the COVID-19 pandemic, by establishing the position of Associate Director for Student Support. We will improve sustainability by developing a PCI-specific F-award path to submission program. While the PCI is disease-agnostic, many of our trainees have undertaken research that is highly relevant to our catchment area, particularly in relation to infectious disease, cancer, and brain science. During the next funding period, we seek to leverage the non-categorical PCI and develop new Research Focus Areas in Infectious Disease, Cancer Outcomes, and Brain Sciences, to integrate highly funded mentors and provide the opportunity to bring additional disease-specific T32 grants into PCI, providing PCI trainees funding opportunities beyond the four disease-agnostic slots sought through this application. While our training approach will remain non-categorical, in the next project period we will seek to emphasize these focus areas per our institutional strengths, while applying TS and HE lenses to all trainees' projects.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14969", "attributes": { "award_id": "5R21AI178831-02", "title": "Anti-inflammatory activity of hydrogels designed to capture extracellular inflammasomes", "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": 6717, "first_name": "Conrad M.", "last_name": "Mallia", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-01", "end_date": "2025-06-30", "award_amount": 183186, "principal_investigator": { "id": 27585, "first_name": "Eva", "last_name": "de Alba Bastarrechea", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2040, "ror": "https://ror.org/00d9ah105", "name": "University of California, Merced", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Multiprotein complexes known as inflammasomes form in innate immune cells to trigger inflammation upon detection of pathogens or tissue damage. Abnormal inflammasome activation leads to chronic inflammation, which is the culprit of numerous life-threatening diseases such as cancer, diabetes, cardiovascular disorders, and the cytokine storm in SARS-CoV-2 infection. Inflammasome assembly is controlled by protein-protein interactions as it requires the self-association and oligomerization of multiple copies of three proteins: sensors to detect danger signals, a protease to activate inflammatory factors, and the adaptor protein ASC to connect sensor and protease. Inflammasome formation leads to plasma membrane rupture and concomitant cell death, thus resulting in the release of proinflammatory cytokines and inflammasome particles to the extracellular environment. These extracellular inflammasomes are internalized by nearby cells to perpetuate and amplify the inflammatory response. Removing or sequestering extracellular inflammasomes will likely inhibit or reduce inflammation. Therefore, extracellular inflammasomes are potential therapeutic targets. Our laboratory’s extensive experience on the function and structure of the adaptor ASC, and its interactions with other inflammasome proteins, has led us to create hydrogels designed to form specific protein-protein interactions with inflammasomes; thus, they have the potential to broadly inhibit inflammation by effectively capturing and removing extracellular inflammasomes. This project focuses on identifying the hydrogelation factors leading to optimum biding of inflammasome particles in cell-free systems (Aim 1); and determining the anti-inflammatory efficiency of the hydrogels in the presence of activated innate immune cells (Aim 2). Our experimental plan will combine cell biology and biochemical approaches, including live/dead cell imaging, flow cytometry, immunoblotting, enzyme-linked immunosorbent assays and fluorescence spectroscopy. Overall, we expect to develop a hydrogel technology of broad applicability to reduce inflammation in the absence of drug loading by targeting the inflammasome, which is implicated in many inflammatory diseases.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15051", "attributes": { "award_id": "5K23HL168212-02", "title": "Individualizing Steroid Use in Pneumonia", "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": 22653, "first_name": "EMMANUEL FRANCK", "last_name": "Mongodin", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-06-01", "end_date": "2028-05-31", "award_amount": 169020, "principal_investigator": { "id": 27399, "first_name": "Yewande", "last_name": "Odeyemi", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1426, "ror": "", "name": "MAYO CLINIC ROCHESTER", "address": "", "city": "", "state": "MN", "zip": "", "country": "United States", "approved": true }, "abstract": "Pneumonia is the leading infectious cause of death worldwide. While inflammation is a hallmark pathologic feature of pneumonia, the use of corticosteroids to blunt the profound inflammatory response remains undefined. Decades of studies in heterogeneous populations failed to show a consistent benefit, leading to conflicting guidelines on the use of corticosteroids. Although corticosteroids have been shown to be effective in COVID-19 pneumonia, the use of corticosteroids in other infectious pneumonia remains unclear with high variability in clinical practice. This variability in practice presents an opportunity to see how corticosteroid administration in pneumonia can be optimized and tailored to patient specific characteristics. The objective of this study is to adapt advanced statistical and machine learning methods to already available robust observational data from the electronic health record to identify predictors of clinical deterioration and to develop an individualized treatment rule for steroid use in patients with community acquired pneumonia. This will be accomplished through three specific aims: 1) To develop and validate a machine learning prediction tool for in-hospital disease progression, 2) To develop and test an individualized treatment rule (ITR) for steroid use, and 3) To conduct a single center feasibility clinical trial comparing ITR and biomarker guided corticosteroid use and dosing to usual care in patients with community acquired pneumonia. We hypothesize that: 1) a combination of demographics, physiological parameters, clinical and laboratory data will be accurate in predicting risk of in-hospital disease progression and identifying steroid-responsive patients in whom benefit from adjunct corticosteroid treatment outweighs potential harm, and 2) ITR and biomarker-guided corticosteroid use, and dosing will be feasible. This career development award will provide important preliminary data for future larger clinical trials focused on optimizing corticosteroid use in pneumonia while training a junior investigator in the essential skills needed to become an independent researcher.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14886", "attributes": { "award_id": "1R01NS136806-01", "title": "Cerebral Energy Metabolism in ME/CFS with and without PASC", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Neurological Disorders and Stroke (NINDS)" ], "program_reference_codes": [], "program_officials": [ { "id": 10999, "first_name": "Vicky R", "last_name": "Whittemore", "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": 670721, "principal_investigator": { "id": 23743, "first_name": "Xiang", "last_name": "Xu", "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": "Many patients who have recovered from SARS-CoV-2, the virus that causes COVID-19, continue to experience a constellation of symptoms long after the initial illness. Known as “long-COVID”, or Post- Acute Sequelae of SARS-Cov-2 infection (PASC), the most frequently reported symptoms are fatigue, post exertional malaise and cognitive dysfunction, which are also the primary symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Many of the PASC patients fulfill diagnostic criteria for ME/CFS, but differ from non-PASC ME/CFS patients in that they share a common infectious trigger and have a shorter duration of illness, which reduces heterogeneity. Understanding whether PASC ME/CFS shares overlapping mechanisms with non-PASC ME/CFS is critical, as this could provide insights into the mechanisms and inform treatment strategies of ME/CFS in general. To address this question, we propose a comparison study of PASC ME/CFS patients with sudden onset illness to non-PASC ME/CFS patients who reported a sudden flu-like illness onset. Limited studies have shown reductions in cerebral blood flow and increased cerebroventricular lactate in ME/CFS patients suggesting alterations in perfusion and metabolic properties. Our recent preliminary results show that the oxygen extraction fraction was elevated in PASC ME/CFS patients, which may be attributed to reduced cerebral blood flow and mitochondrial dysfunction. In this project, we aim to conduct non- invasive brain magnetic resonance imaging (MRI) to compare the similarities and differences in cerebral oxygen and glucose metabolism between the two patient groups as well as healthy controls. We will measure and compare the oxygen extraction fraction, cerebral blood flow, and cerebral metabolic rate of oxygen and glucose uptake and metabolic rate in the patient groups and healthy controls. The MRI derived parameters will then be correlated to the disease symptom burden. Additional, since many PASC patients recover over one year, we aim to perform a follow-up study on the PASC and non-PASC ME/CFS groups. Completion of this timely and important study will provide comparison of PASC and non-PASC ME/CSF in terms of changes in glucose and oxygen metabolic properties, as well as how these imaging parameters are related to the disease burden. Through analysis of the longitudinal data, we will be able to determine whether the changes in metabolic properties are associated with changes of patient reported outcome measures. The knowledge learned will deepen our understanding of the ME/CFS/PASC (long-COVID) disease mechanisms, aid in ME/CFS diagnosis, inform treatment decisions, and inspire new treatment targets.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15020", "attributes": { "award_id": "5R01CA277738-02", "title": "A dyadic exercise approach to prevent declines in physical and mental health in couples during radiation treatment for cancer: a hybrid type I efficacy-implementation trial", "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": 27622, "first_name": "AMANDA MARIE", "last_name": "Acevedo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-01", "end_date": "2028-06-30", "award_amount": 525495, "principal_investigator": { "id": 27623, "first_name": "KERRI M", "last_name": "WINTERS-STONE", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 765, "ror": "https://ror.org/009avj582", "name": "Oregon Health & Science University", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "Breast and prostate cancer are two of the most common and survivable cancers and most survivors of these cancers will be married when diagnosed. Compared to couples that aren't facing a chronic illness, both cancer survivors and their spouses suffer from poorer physical and mental health that leads higher morbidity and mortality. Since couples experience and navigate an illness together their health becomes intertwined, thus programs aimed at one member of the dyad ignore the interdependent nature of the couple. Exercise improves quality of life among cancer survivors; but, we were the first to adapt exercise to be a partnered activity that amplifies the dose of exercise and builds teamwork to improve dyadic outcomes (i.e., physical and mental health of patients and partners). We developed and piloted Exercising Together in prostate cancer survivors and their spouses long after his diagnosis. The pilot showed that six months of partnered exercise could improve physical and mental health in both partners as well as their intimate relationship. We believe the program would be most effective at mitigating the impact of newly diagnosed cancer and treatment on the physical and mental health of each partner if implemented much earlier in the point of care for patients. We have preliminary data on 10 couples who participated in an adapted version of Exercising Together during his radiation treatment for prostate cancer (6-8 weeks). The adapted program is much shorter (8 v. 24 wks.) than the original and is more focused on developing teamwork as a mechanism to amplify the benefits of exercise on dyadic outcomes. All couples completed the program and improved physical and mental health and their level of communication; however, we had no control group so we cannot be certain if the program is efficacious or not nor how long lasting the effects of the program might be. We now propose a Type I hybrid effectiveness-implementation trial of Exercising Together adapted for the radiation oncology setting. This design allows us to formally test the efficacy of a clinic- based version of Exercising Together using a randomized controlled design, a larger sample, a broader set of outcomes, and a follow-up period. We will also examine putative dyadic mechanisms to explain how our intervention improves dyadic health. At the same time, we will gather critical information from multiple stakeholders to inform future implementation approaches to integrate Exercising Together into the care plan for cancer patients. We propose a randomized controlled Phase II trial in 200 couples who will be randomly assigned to participate in an 8-week program of Exercising Together at the start of his/her radiation therapy or to a usual care control group that receives standard exercise guidance and receipt of a video of the couples program at the end of participation. Couples are tested at baseline, post-intervention (2 mos.), and 4- and 6-mos. follow up. Based on adaptations in other trials developed during COVID19, exercise training and assessments will be delivered through remote technology, which allows us to better diversity the sample and widen the scalability of the program.", "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": "14985", "attributes": { "award_id": "5K99DK133502-02", "title": "Mechanisms of mitochondrial-ER communication during dietary and thermal induced stress", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)" ], "program_reference_codes": [], "program_officials": [ { "id": 20615, "first_name": "MAREN R", "last_name": "LAUGHLIN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-07-01", "end_date": "2025-06-30", "award_amount": 90000, "principal_investigator": { "id": 27594, "first_name": "Pedro Antonio", "last_name": "Latorre Muro", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 997, "ror": "", "name": "DANA-FARBER CANCER INST", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Obesity is a pandemic affecting 40% of the population that increases the risk of serious metabolic diseases including type 2 diabetes and severe forms of SARS-CoV2 infection. Obesity reduces insulin sensitivity and dysregulates glucose homeostasis sustaining high blood glucose levels and the development of type 2 diabetes. Activation of brown adipocytes (BAs) is a promising approach to treat obesity and associated diseases. Brown adipocytes rely on an extensive network of mitochondria that increases energy expenditure and maintains glucose homeostasis through glucose, amino acid, and fatty acid oxidation. During fat-induced stress, mitochondrial-endoplasmic reticulum (ER) communication sustains cellular function in BAs. However, the mechanisms by which mitochondrial-ER communication shapes cellular adaptation during obesity are poorly understood. Therefore, studying these pathways will provide new therapeutical approaches to target obesity. The main goal of this application is to study the mechanisms of mitochondrial-ER communication that ensure mitochondrial function and cellular homeostasis during diet-induced stress. We have described that in BAs mitochondrial-ER communication promotes thermogenesis during cold stimulation through the ER-resident kinase PERK. To follow up this work, in Aim 1, the effects of long-term high fat diet (HFD) will be studied in UCP1-Cre PERK-/- mice exposed to different dietary and bioenergetic conditions. Our preliminary information suggests that PERK may be signaling to the chaperone PPID to control mitochondrial protein import. In Aim 2, structural approaches using Cryogenic Electron Microscopy (CryoEM) will be used to explore the molecular interactions that control and maintain mitochondrial functions in BAs including mitochondrial protein import, focusing on PPID-dependent pathway, and cellular respiration during dietary and thermal stress. Finally, in Aim 3 the role of PPID in physiology and cellular functions will be studied in mice exposed to diet and thermal stress. While Aims 1 and part of 2 will be completed during the training stage, part of Aim 2 and the entire Aim 3 will be conducted during the independent phase of the award. The extensive training in different fields proposed in this application including physiology and cellular and structural biology will provide the tools to become an independent researcher and study the mechanisms of inter- organalle communication that regulate mitochondrial biogenesis and cellular metabolism. This training will be received in the vibrant scientific communities of Dana-Farber Cancer Institute and Harvard Medical School. This environment will expose me to the collaborations and discussions necessary for career development and future opportunities. Dr. Puigserver mentorship will be supportive to establish those connections and actively guide me in talk and manuscript preparation, student mentorship, experimental design, and career development. Together, the research and career development plans proposed in this application will strengthen my skills and competitiveness to become an independent researcher at a major institution.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "15059", "attributes": { "award_id": "5R33HL168751-02", "title": "A New Lipid Nanoparticle Technology Enabling Long-acting mRNA Therapy", "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": 22565, "first_name": "ILANA GRACE", "last_name": "Goldberg", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-06-15", "end_date": "2025-05-31", "award_amount": 513877, "principal_investigator": { "id": 27651, "first_name": "Jinjun", "last_name": "Shi", "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": "Recent clinical success of mRNA vaccines for COVID-19 has sparked enormous interest in mRNA therapy for a wide range of biomedical applications including protein replacement therapy. However, one unique challenge associated with mRNA therapy is dealing with the transient efficacy due to its relatively short half-life. Current nanoparticles including FDA-approved lipid nanoparticles (LNPs) could significantly improve mRNA translation efficiency, but the duration of in vivo protein expression by these mRNA NPs is generally short (limited to a few days), thus requiring frequent re-dosing. The main objective of this project is to advance a new transformative LNP technology enabling long-acting mRNA replacement therapy of genetic disorders associated with loss of function of a particular protein. In our recent studies, we developed a new generation of LNPs and performed the head-to-head comparison in vitro and in vivo to the benchmark LNP formulations composed of FDA-approved ionizable lipids. We observed a dramatic increase of the duration of model protein expression in vitro and in vivo by our new mRNA LNPs. Preliminary safety studies showed that our mRNA LNPs were well tolerated without observable adverse events in vivo. With the proof-of-concept demonstration of our long-acting mRNA LNPs, this project aims to i) further optimize the mRNA LNP technology for longer-term, high level protein expression, and ii) rigorously validate this transformative mRNA delivery platform using hemophilia A as a model disease. We expect that with successful validation in normal and hemophilia A mice, this long-acting mRNA LNP platform could be readily moved into clinical testing for hemophilia and expanded to other genetic diseases that require restoration of normal protein functions.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14894", "attributes": { "award_id": "1R01AI178605-01A1", "title": "A NOVEL STRATEGY TO INHIBIT SARS-COV-2 INFECTION AND COVID-19", "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": 6115, "first_name": "DIPANWITA", "last_name": "Basu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-06-13", "end_date": "2029-04-30", "award_amount": 697983, "principal_investigator": { "id": 31583, "first_name": "PHILIPPE ANDRE", "last_name": "GALLAY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 745, "ror": "", "name": "SCRIPPS RESEARCH INSTITUTE, THE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "While the development of effective vaccines against CoV-2 is cause for optimism, vaccine hesitancy in developed countries and shortages in low-income countries are jeopardizing efforts to curb the pandemic. Out of the 6.4 billion people living in low-income countries, only 2% have access to vaccines. Consequently, the conditions are ripe for continued spike mutation and evolution to increasingly transmissible strains causing more severe illness. Some of these emerging strains may even challenge the protection of vaccines. In this application, we propose a novel therapeutic approach for the eradication of CoV-2. We developed a new strategy, which consists of hijacking the viral replication machinery to trigger the death of CoV-2-infected cells, while preserving uninfected cells. We propose to administer intranasally human ACE2 transgenic mice and Syrian hamsters a “tailored” RNA encoding the diphtheria toxin fragment A (DTA) called {CoV-2 Hijack DTA} that is only recognized and transcribed by the CoV-2 polymerase (Pol/RdRp) present in infected cells, triggering DTA expression and rapid death of infected cells. Since DTA cannot cross the cellular membrane, it cannot kill uninfected cells. Because RNA can be easily broken down in the body, it needs to be transported within a protective carrier. Noninvasive aerosol inhalation is a well-established method of drug delivery to the respiratory tract and represents an ideal route for nucleic-acid-based therapeutics as demonstrated in various clinical trials. We propose to design degradable polymer-lipid nanoparticles (LNPs) that can deliver RNAs by nebulization (inhalation) to the respiratory tract. We propose to synthesize hyperbranched poly-beta amino esters (hPBAEs) to enable nanoformulation by nebulizer of stable and concentrated polyplexes suitable for inhalation. This strategy should achieve uniform distribution of RNAs throughout lungs resulting in high levels of proteins of interest 24h post-inhalation of hPBAE polyplexes without local or systemic toxicity due to rapid degradation of hPBAE vectors. The safety and antiviral efficacy of nebulized {CoV-2 Hijack DTA} RNA LNPs stably protected by degradable hPBAEs will be analyzed. Our in vivo imaging IVIS Lumina S5 system permits a daily bioluminescence (NanoLuc-CoV-2) or fluorescence (mNeonGreen CoV-2) quantification of the {CoV-2 Hijack DTA} RNA LNPs-mediated killing of infected lungs in live animals. We will investigate the MoA causing the killing of CoV-2-infected cells by {CoV-2 Hijack DTA}. We will use complementary approaches to determine whether {CoV-2 Hijack DTA} triggers apoptosis, membrane permeability and/or chromosomal degradation leading to cell killing. By scRNA-Seq, we will analyze i) the specific killing of infected cells at high resolution on large numbers of cells exposed to {CoV-2 Hijack DTA}; ii) the global map of apoptotic DNA breakpoints such as DNA fragmentation; and iii) the phenotype of immunological target cells. We will examine whether {CoV-2 Hijack DTA} RNA LNPs counteract the deleterious inflammatory response, which occurs during CoV-2 infection including histopathological lesion development, interstitial pneumonia and cytokine cascade.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14946", "attributes": { "award_id": "5R01HL169760-02", "title": "Bispecific immunotherapeutic delivery system for lung diseases", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 22589, "first_name": "CHRISTIAN RENE", "last_name": "Gomez", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-08-01", "end_date": "2027-05-31", "award_amount": 905828, "principal_investigator": { "id": 28090, "first_name": "Jan Eugeniusz", "last_name": "Schnitzer", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2076, "ror": "", "name": "PROTEOGENOMICS RESEARCH INSTIT/SYS/ MED", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Modern medicine has created precision drugs blocking a single therapeutic target like TGF-β with high affinity and specificity. Yet treating lung diseases remains challenging in part because lung microvascular endothelium represents a key restrictive barrier to effective drug delivery. Current systemic therapeutics rely solely on convection and diffusion to extravasate passively into the tissue interstitium where disease targets and cells can readily be reached and directly treated. The goal of this research proposal is to design, develop and test a novel drug delivery system for immunotherapeutics that overcomes this key barrier by targeting caveolae to facilitate active and specific transcytosis into lungs after intravenous injection. The ideal is to deliver the entire therapeutic dose inside the lung tissue with all other tissues minimally exposed. We attempt to approach this ideal by achieving robust transendothelial pumping precisely into lung tissue to comprehensively block the therapeutic target TGF-β, which regulates inflammation and remodeling in diseased tissues. Because TGF-β also exerts various homeostatic effects in many organs, caution is necessary when systemic targeting of its function is attempted. Precision lung targeting proposed here will maximize efficacy and therapeutic indices by minimizing dosages, eliminating toxicities, and reducing cost of treatment. To that end, we have genetically engineered the first “dual precision” immunotherapeutics, namely bispecific antibodies in quad format with one arm pair mediating precise binding/delivery to and penetration of lung tissue via caveolae pumping and the other pair constituting the precision therapeutic modality that blocks TGF-β effector function. Active transendothelial delivery improved precision lung targeting by 100-fold over standard passive transport. Delivering most of the injected dose into lungs within 1 hour enhanced therapeutic potency by >1000-fold in a rat pneumonitis model. Now our goal is to expand this promising preliminary work and further improve and rigorously test this drug delivery system to treat key lung diseases at distinct stages ranging from early acute inflammation to chronic and progressive fibrosis. We will optimize lung targeting of our dual precision immunotherapeutics and study their specific lung delivery, penetration, accumulation, localization, and therapeutic impact in rats using multiple imaging techniques (SPECT-CT, IVM, EM, and IHC). Therapeutic effects will be assessed in a rat bleomycin model that reproduces pathological hallmarks of many fatal human diseases including ALI, ARDS, COVID, pneumonias, and fibrosis. Our specific aims are: 1) to engineer and evaluate distinct caveolae-targeted antibody constructs for precision active delivery into normal lung tissue, 2) to quantify targeting and optimize delivery of bispecific immunotherapeutics in lung disease, 3) to test efficacy of bispecific immunotherapeutics to ameliorate lung disease and block TGF-β pathways. This work sets a foundation for caveolae-targeted therapies and could begin a paradigm shift from passive to active drug delivery for many diseases.", "keywords": [ "Acute", "Acute Respiratory Distress Syndrome", "Address", "Affect", "Affinity", "Animals", "Antibodies", "Antiinflammatory Effect", "Automobile Driving", "Binding", "Biodistribution", "Biological Markers", "Biological Products", "Bispecific Antibodies", "Bleomycin", "Blood Vessels", "COVID-19", "Cause of Death", "Caveolae", "Cells", "Cessation of life", "Chimeric Proteins", "Chronic", "Clinical", "Convection", "Cytokine Signaling", "Data", "Diffusion", "Disease", "Dose", "Drug Delivery Systems", "Drug Targeting", "Endothelial Cells", "Endothelium", "Engineering", "Exhibits", "Extravasation", "Fibrosis", "Foundations", "Genetic Engineering", "Goals", "Histopathology", "Hour", "Image", "Imaging Techniques", "Immunotherapeutic agent", "In Vitro", "Inflammation", "Inflammatory", "Intravenous", "Lung", "Lung Diseases", "Magic", "Mediating", "Modality", "Modeling", "Modern Medicine", "Organ", "Pathologic", "Pathology", "Pathway interactions", "Penetration", "Pharmaceutical Preparations", "Phosphorylation", "Physiology", "Pneumonia", "Pre-Clinical Model", "Precision therapeutics", "Preclinical Testing", "Property", "Pulmonary Inflammation", "Pulmonary Pathology", "Pump", "Rattus", "Research Proposals", "Rodent", "Signal Transduction", "Site", "Specificity", "Structure of parenchyma of lung", "System", "Testing", "Therapeutic", "Therapeutic Effect", "Therapeutic Index", "Time", "Tissues", "Toxic effect", "Transforming Growth Factor beta", "Treatment Cost", "Treatment Efficacy", "Vascular Endothelial Cell", "Vascular Endothelium", "Work", "Workplace", "arm", "comparative", "design", "dosage", "drug testing", "efficacy testing", "expectation", "human disease", "improved", "intravenous injection", "novel", "novel therapeutics", "passive transport", "pneumonitis and fibrosis", "precision drugs", "prevent", "prophylactic", "protein expression", "prototype", "research clinical testing", "response", "single photon emission computed tomography", "targeted treatment", "therapeutic target", "therapy outcome", "transcytosis", "uptake" ], "approved": true } } ], "meta": { "pagination": { "page": 2, "pages": 1392, "count": 13920 } } }