Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1383&sort=end_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=end_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1397&sort=end_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=end_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1382&sort=end_date" }, "data": [ { "type": "Grant", "id": "14856", "attributes": { "award_id": "1R37CA285794-01A1", "title": "Targeting tumoral Lactobacillus iners to improve outcomes in cervical cancers", "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": 31541, "first_name": "Avraham", "last_name": "Rasooly", "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": 660742, "principal_investigator": { "id": 31542, "first_name": "Lauren Elizabeth", "last_name": "Colbert", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1420, "ror": "", "name": "UNIVERSITY OF TX MD ANDERSON CAN CTR", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Cervical cancer remains the second most common cancer killer of women worldwide, with an annual incidence of more than 600,000 and an annual death rate of 300,000. Further, cervical cancer disproportionately affects communities of medically underserved and minority women within the US and abroad, and improved therapies are urgently needed. Primary and secondary prevention approaches are also variably effective – even prior to the COVID-19 pandemic, just 1 in 8 girls was vaccinated against human papillomavirus (HPV), the cause of 90% of cervical cancers. Vaccination rates also dropped sharply during the pandemic, even in the United States. Current World Health Organization (WHO) estimates of HPV vaccine uptake rates is 21%. The vast majority of cervical cancers that are diagnosed after primary and secondary prevention fail are locally advanced cervical cancer (LACC). Approximately 40% of women diagnosed with LACC will relapse and die of disease even with standard-of-care curative treatment, cisplatin-based chemoradiotherapy (CRT). CRT has remained the standard-of-care for more than two decades, and novel approaches have failed to improve outcomes. We have identified a critical prognostic factor, a bacteria called Lactobacillus iners (L. iners), in the cervical tumor microbiome, which rewires tumor metabolism to utilize lactate and is associated with treatment resistance and poor survival. Further, commensal Lactobacilli (lactic acid bacteria) in other tumor sites often driven by lactate, such as head and neck and lung cancers, also appear to lead to treatment resistance and poor survival. Our objective is to understand specifically how L. iners and other lactic acid bacteria influence cancer cell and immune cell metabolism using state-of-the-art proximity proteomics and mass cytometry (Aim 1). We will also test novel therapeutic approaches to target either tumor resident bacteria by eliminating or replacing specific bacterial species (Aim 2), or metabolic effects of tumor resident bacteria via local bacterial engineering or systemic metabolism targeting anti-cancer therapies (Aim 3). Targeting cervical tumor bacteria as a therapeutic (“Bugs as Drugs”) is a paradigm-shifting idea, capitalizing on the relative simplicity of the cervicovaginal microbiome and its tendency to be dominated by Lactobacillus species, and not only will this study lead to improved microbiome- based therapeutics to improve outcomes in cervical cancer, but this proof-of-concept model could be used to inform tumor microbiome-based therapeutics across cancer types.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14861", "attributes": { "award_id": "1K08CA286762-01", "title": "Calming the Cytokine Storm: Unraveling the Biology of CRS and ICANS", "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": "2024-07-01", "end_date": "2029-06-30", "award_amount": 248509, "principal_investigator": { "id": 31546, "first_name": "Caroline", "last_name": "Diorio", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1073, "ror": "", "name": "CHILDREN'S HOSP OF PHILADELPHIA", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Chimeric antigen receptor T-cells (CART) have revolutionized cancer therapy. However, CART cause two common and severe toxicities: Cytokine Release Syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). CRS and ICANS are overlapping phenomena that occur with a spectrum of severity from mild to life threatening. Effective therapies for CRS currently exist but severe refractory cases still occur. Effective therapies for ICANS are lacking. The pathophysiology of CRS and ICANS have not yet been fully defined, precluding development and translation of novel therapies. In particular, the role of the host innate immune system in these conditions is poorly understood. The specific objective of this project is to identify the cellular and cytokine initiators of CRS and the role of complement and the inflammasome in the biology of ICANS. In Specific Aim 1, the candidate will determine the number and transcriptional activation state of different monocyte and non-monocyte populations associated with CRS using single cell RNA sequencing (scRNAseq) and test the role of novel monocyte produced cytokines in the priming and initiation of CRS. In Specific Aim 2, the candidate will dissect the role of the inflammasome and complement dysregulation in the development of ICANS, and test individual and combined approaches for inflammasome and complement blockade in preventing and treating ICANS. The candidate is a pediatric oncologist committed to understanding immune dysregulation disorders that occur as a consequence of cancer immunotherapy. The proposed training plan and research project will be conducted at the Children's Hospital of Philadelphia (CHOP) and the University of Pennsylvania (UPENN). CHOP and UPENN are leaders in cellular immunotherapies and basic and clinical immunology and will provide an outstanding environment in which to conduct the proposed research. Throughout the period of the award the candidate will be mentored by Dr. David Teachey and a very strong advisory committee including Drs. Ed Behrens, Marcela Maus, Wenchao Song and Stephan Grupp. The long-term goal of the candidate is to develop a research program devoted to understanding the role of the innate immune system in immune dysregulation related to cancer immunotherapies, and improving the health of patients by facilitating translation of less toxic, more effective immunotherapies. Completion of the proposed research project and the complementary training plan will provide a robust foundation to achieve this goal.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14863", "attributes": { "award_id": "1T32GM153182-01", "title": "University of Washington Medical Scientist Training Program", "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": 31549, "first_name": "Andrea", "last_name": "Keane-Myers", "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": 1798078, "principal_investigator": { "id": 31550, "first_name": "MARSHALL S.", "last_name": "HORWITZ", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "The University of Washington (UW) Medical Scientist Training Program (MSTP) was established in 1970 and is the only MD-PhD program in the five “WWAMI” states (Washington, Wyoming, Alaska, Montana, and Idaho) comprising a quarter of the landmass of the United States. Our program has thus far produced 285 graduates, 78% of whom have been employed in scientific research throughout their careers. Our goal is to leverage institutional and national resources to build an educational pipeline leading to the development and identification of a diverse group of talented trainees and equip them with the skills, mentorship, role models, and motivation required to advance the frontiers of biomedical science and technology. Among multiple accomplishments, students and graduates of our program created the Apple Macintosh computer and one of the first enzyme replacement therapies for metabolic disease, have provided fundamental insights into the nature of stem cells, the sequence and structure of the human genome, and the infectivity of SARS-CoV-2, and have led similarly successful MD-PhD programs elsewhere, thereby exponentially amplifying our program’s impact on training the next generation of physician-scientists. Our competitive program has grown to an annual class of 15, comprising approximately one-fifth of all medical students in Seattle. For each offer of admission, we receive over 23 training- grant-eligible applications. Of our 96 current trainees, 21% are from populations under-represented in medicine and 19% are from disadvantaged backgrounds. Our partnership with Morehouse School of Medicine enriches both institutions. Our trainees carry out their PhD research with UW faculty mentors at the UW, Fred Hutchinson Cancer Research Center (Hutch), Seattle Children's Hospital Research Institute, and Benaroya Research Institute. Current trainees' PhD departments and programs include Molecular and Cellular Biology, Neuroscience, Genome Sciences, Bioengineering, Computer Science, Molecular Engineering, Chemistry, and Epidemiology. They are mentored by a highly trained group of 81 well-funded, diverse, and gender-balanced distinguished faculty drawn from across ranks of junior to senior investigators, who emphasize and practice responsible, reproducible science in safe training environments. Our program integrates medical and graduate education, while reducing redundancy. Mean time to completion is 8.3 years and on a shortening trajectory, with minimal attrition of 2.6%. Over half of trainees receive NIH F30 independent fellowships. Over the last 15 years, graduates published a mean of 6.7 peer-reviewed papers, including 2.8 as first-authors, many of which are exceptionally impactful and have altered the course of research in their fields. Nearly all graduates go on to research-related residencies at leading institutions, predominantly in fields conducive to long-term retention in research. We continually evaluate our outcomes, measure our progress toward its overarching objective of producing resilient physician-scientists pushing the envelope at the interface of science and medicine, and iteratively evolve our program to stay at the forefront of evidence-based innovations in training practices.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14868", "attributes": { "award_id": "1K08CA289948-01", "title": "Targeted delivery of a VEGF‐blocking scFv by CD70 CAR‐T cells to enhance anti‐tumor activity in renal cell carcinoma", "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": 27928, "first_name": "Susan E", "last_name": "Lim", "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": 297728, "principal_investigator": { "id": 31557, "first_name": "Mark", "last_name": "Leick", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 736, "ror": "https://ror.org/002pd6e78", "name": "Massachusetts General Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "Although chimeric antigen receptor (CAR)-T cells drive dramatic and durable remissions in patients with B-cell malignancies, responses in solid tumors have been more challenging. There is a dearth of highly effective “armoring” strategies for CAR-T cells to generate additional proteins that augment CAR-T cell function and modulate the tumor microenvironment (TME). Our long-term goal is to develop safe and effective CAR-T cell therapies for solid tumors. The overall objective is to determine the effect of locally secreted VEGF blockade on CD70 CAR-T cell function, safety, and anti-tumor efficacy in renal cell carcinoma (RCC). Our central hypothesis is that locally secreted VEGF blockade will prevent CAR-T cell exhaustion while blocking angiogenesis/tumor growth, and pathologic endothelial activation. The underlying rationale is that determination of the preclinical therapeutic efficacy and associated mechanisms of locally secreted VEGF- blockade will offer a strong scientific framework for new strategies to cancer therapy. To attain the overall objective, we will pursue two specific aims: (1) Determine the effect of secreted VEGF blockade on CD70- CAR-T cell biology ; and (2) Define the capacity for CD70-CAR-T cells with secreted VEGF blockade to modulate RCC tumor proliferation, angiogenesis, and endothelial activation in vivo. Approaching the project, the candidate will examine each side of the immune synapse, in turn, by (1) defining the effects of anti-VEGF single chain variable fragment (scFv) secretion on CAR-T cells through the underlying CD70 CAR-T biology and honing in on the site of actions of the VEGF-scFv (paracrine, autocrine, or intracrine) (Aim 1), and (2) determining the effects of anti-VEGF scFv secretion on RCC tumor cells, angiogenesis, and endothelial activation via in vivo orthotopic RCC tumor models, cytokine release syndrome models, and VEGF-blockade cardiovascular toxicity models (Aim 2) The applicant, Dr. Mark Leick, an oncologist at the Massachusetts General Hospital (MGH) spends 80% of his time in translational research and 20% in clinical practice caring for patients with cancer. He has outlined a five-year career development plan consisting of coursework, conferences, seminars, and structured mentoring in experimental design, mouse modeling, angiogenesis and VEGF signaling pathways, CAR-T signaling, and renal cell carcinoma to acquire the necessary skills required to perform his research and to reach his goal of becoming an independent investigator in translational research. His research is directly relevant to the mission of the NCI to conduct cancer research to advance scientific knowledge and help all people live longer healthier lives using immune cell therapies. Supervising Dr. Leick’s mentorship and training is Dr. Marcela Maus, a worldwide leader in cellular immunotherapy. Dr. Leick will conduct this research at MGH and leverage the exceptional research and teaching environments of his scientific advisory committee (MGH, Dana Farber Cancer Institute, Beth Israel Deaconess Medical Center, and Boston Children’s Hospital).", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14870", "attributes": { "award_id": "1U18HS029950-01", "title": "Keck COVID Recovery Clinic Optimal Outcomes for Patients, a Comprehensive Assessment and Management Program", "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": 22615, "first_name": "Brent", "last_name": "Sandmeyer", "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": 999331, "principal_investigator": { "id": 31560, "first_name": "Caitlin Helen", "last_name": "McAuley", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 152, "ror": "https://ror.org/03taz7m60", "name": "University of Southern California", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "SUMMARY/ABSTRACT Post Acute Sequelae of COVID-19 (PASC) may affect 15 to 30% of people infected with COVID-19, which would suggest at least 1 million cases in Los Angeles (LA) County and at least 7 million cases in the United States. The COVID Recovery Clinic at Keck Medicine (Keck CRC) of the University of Southern California (USC) was established in 2020 to treat patients with PASC symptoms. Keck CRC operates under an interdisciplinary, collaborative care model, and brings together a primary care physician, occupational therapist, physical therapist, social worker, respiratory therapist, medical assistant, nurse (RN) navigator, and support coordinator. Keck CRC is well positioned at Keck Medicine of USC and in LA County to accomplish goals to expand and optimize clinical care of PASC, as well as to be a center for dissemination of education and project findings across LA County and nationally across other similar clinics. Through this funding opportunity, the Keck CRC will establish the Keck COVID Recovery Clinic, Optimal Outcomes for Patients in a Comprehensive Assessment and Management Program (Keck CO-OP CAMP). This program will pursue four main goals, in alignment with the eight characteristics of Long COVID clinics specified in the Funding Opportunity “Purpose of the NOFO” (RFA-HS-23-012): Goal 1: Improve current care delivery and system model within Keck CRC (NOFO 1, 2, 3, 4). Activities under this goal will optimize and update the current Keck CRC care model through expanding dedicated staff time and roles, creating and adapting clinical workflows, improving care coordination, establishing mechanisms for oversight, and utilizing data collection and analysis. Goal 2: Establish new models of service to expand services to more patients experiencing PASC, including those who may be limited from ongoing care through the clinic due to insurance or geographic limitations (NOFO 1, 2, 3, 5). Activities under this goal will include creating additional consultation services in-person and virtually, connecting with clinics that may benefit from our resources, adding a support group, and educating patients, caregivers, and healthcare workers. Goal 3: Create multidisciplinary education resources for internal and external providers (NOFO 5, 6, 8). Activities under this goal will include creating clinical workflows, educational materials, and resources, and connecting with clinics that may benefit from Keck CRC resources. Goal 4: Implement consistent and standardized data collection on patient and clinic outcomes, with regular periodic assessment of data, to inform ongoing modifications in care delivery. (NOFO 7, 8). Activities under this goal will include utilizing and adapting technology for data collection, assessment of data, interpretation of data, and dissemination of findings.", "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": "14878", "attributes": { "award_id": "1U18HS029951-01", "title": "Broadening the scale and impact of a comprehensive Long COVID clinic to serve diverse patient groups with multidisciplinary care and research access", "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": 22615, "first_name": "Brent", "last_name": "Sandmeyer", "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": 31570, "first_name": "Vivek", "last_name": "Jain", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31372, "first_name": "Michael Joseph", "last_name": "Peluso", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 31571, "first_name": "Lekshmi", "last_name": "Santhosh", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 768, "ror": "https://ror.org/043mz5j54", "name": "University of California, San Francisco", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Please find attached our application entitled “Broadening the scale and impact of a comprehensive Long COVID clinic to serve diverse patient groups with multidisciplinary care and research access” being submitted to RFA-HS-23-012: Implementing and Evaluating New Models for Delivering Comprehensive, Coordinated, Person-Centered Care to People with Long COVID (U18). This application is responsive to SEN NOT-HS-23-013. While several models of dedicated outpatient Long COVID clinics have emerged across the U.S., features essential to implementing and providing equitable, comprehensive, coordinated, and person-centered Long COVID care have yet to be fully identified and evaluated. In April 2020, our team founded the multidisciplinary UCSF OPTIMAL Long COVID clinic, a dedicated center for individuals in the post- acute phase of COVID-19 modeled after the multidisciplinary structure of post- ICU clinics. The clinic currently serves a diverse population and the clinic has already had a major impact, resulting in lower odds of hospitalization or emergency department visits. The central goal of this proposal is to improve capacity, access, and equity for underserved, vulnerable, and minority populations being served by the OPTIMAL Long COVID Clinic. Specifically, we will scale up multidisciplinary care operations in the current UCSF OPTIMAL Clinic and expand the program to patients at San Francisco General Hospital, a safety net hospital serving a diverse and vulnerable patient population experiencing long COVID. We will increase coordination and communication between our clinical operations, established federally-funded Long COVID research programs, and community- based organizations (CBOs) and clinics serving populations affected by Long COVID. Using an implementation science approach and leveraging the existing OPTIMAL Long COVID care model and established relationships with community organizations and research studies, we will: Aim 1: Scale up Long COVID care in the San Francisco Bay Area to increase access for underserved, vulnerable, and minority populations. Aim 2: Enhance Long COVID care coordination and communication across clinical, research, and community settings. Aim 3: Identify key barriers and facilitators to implementation success and sustainability of the expanded and enhanced Long COVID care model. Results from this project will significantly inform Long COVID care delivery models and have a major impact on unmet Long COVID care needs among underserved populations.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14881", "attributes": { "award_id": "1K25AI177810-01A1", "title": "Understand the mechanism of SARS-CoV-2 entry by single-molecule approaches.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 27781, "first_name": "Mary Katherine Bradford", "last_name": "Plimack", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2024-07-11", "end_date": "2029-06-30", "award_amount": 120258, "principal_investigator": { "id": 31574, "first_name": "Prakash", "last_name": "Shrestha", "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": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its transmission across the world was the cause of the COVID-19 pandemic. The CoV entry is mainly initiated by the binding of furin cleavage activated spike (S) protein with ACE2 receptor protein on the surface of host cell. Next, S2’ cleavage by transmembrane protease serine 2 (TMPRSS2) on the cell surface induce the conformational change of S2 subunit to activate the membrane fusion and entry of virus genetic material. Therefore, S protein has been the major target to design the vaccines and therapeutics. While a handful of investigations have been reported about the structure of S protein:ACE2 complex, critical questions about the detachment of S1/S2 subunits, structural changes in S2 and their dynamics to activate the membrane fusion remain. These answers will help to improve the current understanding of the mechanism of virus entry and should be highly significant for the development of effective preventions and therapeutics. I propose to combine novel DNA nanoswitch calipers (DNC), single-molecule fluorescence integrated optical tweezers, and high-throughput magnetic tweezers to study the dynamics of the molecular events associated with the membrane fusion process of viral entry and analyze the heterogeneity of neutralizing antibodies (nAbs). Using DNC that I developed, we showed the measurement of multiple distances within a target biomolecule at angstrom level precision. Next, we showed the high-throughput measurements in magnetic tweezers to analyze the heterogeneous mixture of peptides. Therefore, DNCs are useful to study multicomponent protein-protein interactions and simultaneously monitor the structural changes associated with the process. By executing these projects, I will have the following three important answers. First, I will measure binding dynamics of full-length S protein and monomer/dimer ACE2 receptor proteins to understand the entire energy landscape governing the interaction of these proteins. Second, I will measure the detachment kinetics of S1/S2 subunits, induced by TMPRSS2 and determine the change in conformation of S2. These reactions are critical to understand the membrane fusion process. Third, I will utilize the similar approach to measure the binding dynamics of nAbs with S protein. By high-throughput measurements in magnetic tweezers, I will analyze the efficacy and heterogeneity of nAbs to understand the immune response of the patients and vaccinated individuals, and also validate DNC assay with a cell-based pseudovirus neutralization assay. Hence, the proposed work will provide detailed insight into understanding the mechanism of SARS- CoV-2 entry and rapid analysis of immune response of the patients. My quantitative approaches and advanced single-molecule approaches will bring insights, into the field of virology and immunology. This study will also give me firsthand experience in biochemistry, molecular biology, virology, and immunology, enabling me to better apply my quantitative and physical training to more topics in biological research in the future.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "14882", "attributes": { "award_id": "1R01DK139924-01", "title": "Macrophage-Targeted Drug Delivery Depot for Obesity and Comorbid Type 2 Diabetes", "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": 26970, "first_name": "RAJATAVA", "last_name": "Basu", "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": 587866, "principal_investigator": { "id": 31575, "first_name": "Andrew Michael", "last_name": "Smith", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1040, "ror": "", "name": "UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "More than 42% of adults in the United States live with obesity, a condition characterized by excess body fat primarily within adipose tissue. Obesity is a risk factor for type 2 diabetes, cardiovascular diseases, cancer, and severe COVID-19 disease and has few widely effective non-surgical interventions. Obesity comorbidities are believed to be triggered by chronic inflammation in adipose tissue, in part caused by infiltration of macrophage cells (MΦs) with adipogenic phenotypes in the obese state. However, the pathogenic role of MΦs is complicated by their diverse and antagonistic roles in adipose metabolism and homeostasis as these cells have the capacity to promote both lipogenesis and lipolysis and promote both tissue hypertrophy and atrophy. Previously, we showed that polysaccharide-based nanocarriers could efficiently deliver drugs to adipose MΦs after intraperitoneal injection. We found that certain classes of these therapies potently modulate MΦ phenotype, induce rapid body weight loss, and reverse diabetic phenotype in obese rodents without changes in food intake. We now propose to develop an extended-release drug depot to deliver these MΦ-targeted nanocarrier drug conjugates to adipose tissue in a translational format designed for high patient adherence. Two primary technological products will be (1) biodegradable composite depots constructed from materials that are efficiently and safely eliminated from the body and (2) translational imaging techniques to longitudinally monitor drug depots in vivo. In Aim 1, we will tune the composition, size, and shape of the depots to generate implants with translational form factors, steady release over 6 months, and minimal foreign body response. We will also validate methods to image and monitor depots by magnetic resonance, ultrasound, and fluorescence modalities. In Aim 2, we will maximize drug loading and redesign the backbone of our targeted nanocarrier and drug linkers for efficient excretion and high solubility. In Aim 3, we will determine mechanisms by which regional depots elicit systemic physiological changes. In Aim 4, we will measure the long-term impact of lead candidate depots on preventing or reversing obesity and obesity-induced diabetes. We will study the dependence of efficacy on sex, hormonal status reflecting menopause, and genetic or dietary obesity origins. If successful, the drug delivery system may provide an urgently needed non-surgical high-adherence strategy to treat patients living with obesity to safely enhance weight loss and prevent or reverse the progression of comorbidities.", "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 } } ], "meta": { "pagination": { "page": 1383, "pages": 1397, "count": 13961 } } }