Grant List
Represents Grant table in the DB
GET /v1/grants?sort=-principal_investigator
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-principal_investigator", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=-principal_investigator", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=2&sort=-principal_investigator", "prev": null }, "data": [ { "type": "Grant", "id": "15805", "attributes": { "award_id": "1K01DA062904-01", "title": "Clinician cannabis use-related preconceptions perpetuating low quality of prenatal care for women who use cannabis during pregnancy", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Drug Abuse (NIDA)" ], "program_reference_codes": [], "program_officials": [ { "id": 32896, "first_name": "SARAH", "last_name": "VIDAL", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-15", "end_date": "2030-06-30", "award_amount": 196236, "principal_investigator": { "id": 32897, "first_name": "Rachel Carmen", "last_name": "Ceasar", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2622, "ror": "", "name": "UNIVERSITY OF SOUTHERN CALIFORNIA", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Cannabis is the most used illicit substance during pregnancy. Rates of self-medicating with cannabis escalated during the COVID-19 pandemic. The scientific objective of this proposal is to investigate the mechanisms contributing to preconceptions about those who use cannabis, especially during pregnancy. The central hypothesis is that preconceptions about those who use cannabis result in negative interactions between patients and clinicians that reduce the quality of healthcare and result in poor outcomes. This innovative project will be the first to: (a) leverage natural language processing/artificial intelligence (NLP/AI) techniques to investigate preconceptions about cannabis use in clinical notes, and (b) investigate associations between cannabis use and prenatal care quality. Research aims will: (Aim 1) Investigate preconceptions about those who use cannabis during pregnancy using a mixed methods approach that integrates NLP/AI and qualitative interviews; (Aim 2) Investigate associations between cannabis use and prenatal care quality among different population groups, such as differences in socioeconomic status and education levels; and (Aim 3) Develop, adapt, and test the feasibility and usability of a clinician training on quality health care practices for those who use cannabis during pregnancy using a multistage modified Delphi process, survey, and qualitative focus groups. This research is complemented by a training plan that builds upon Dr. Rachel Carmen Ceasar’s background in mixed qualitative-quantitative methods and substance use research. The training plan includes using NLP/AI approaches, advanced survey methods in reproductive epidemiology, and implementation science. Together, this research and training will prepare Dr. Ceasar to advance as an independent investigator conducting research on health and substance use among those who are pregnant across the lifespan. The proposed project will improve clinicians’ care of those who use cannabis during pregnancy, providing evidence to inform the development of interventions designed to reduce cannabis-use-related notions in prenatal care.", "keywords": [ "Adverse effects", "American College of Obstetricians and Gynecologists", "Artificial Intelligence", "Belief", "COVID-19 pandemic", "California", "Cannabis", "Caring", "Child Welfare", "Clinical", "Clinical Treatment", "Consensus", "Cross-Sectional Studies", "Data", "Detection", "Education", "Educational Status", "Family", "Focus Groups", "Fright", "Future", "Goals", "Guidelines", "Gynecologic", "Health", "Health Benefit", "Health Care", "Income", "Infant", "Interview", "Knowledge", "Language", "Legal", "Link", "Los Angeles", "Medical", "Medical center", "Mentored Research Scientist Development Award", "Mentors", "Methods", "Modeling", "Moods", "Mothers", "Natural Language Processing", "Nausea", "Outcome", "Output", "Pain", "Patient Outcomes Assessments", "Patients", "Persons", "Policies", "Policy Maker", "Population", "Population Group", "Pregnancy", "Pregnancy Outcome", "Pregnant Women", "Prenatal care", "Prevalence", "Process", "Quality of Care", "Questionnaires", "Recommendation", "Reporting", "Research", "Research Personnel", "Rice", "Risk", "Socioeconomic Status", "Supervision", "Survey Methodology", "Surveys", "Techniques", "Testing", "Time", "Training", "Woman", "authority", "cannabis cessation", "comparative", "efficacy evaluation", "evidence base", "experience", "feasibility testing", "follow-up", "health care delivery", "health care quality", "implementation science", "improved", "indexing", "innovation", "large language model", "life span", "low socioeconomic status", "marijuana use", "marijuana use in pregnancy", "neurodevelopment", "open source", "preconception", "prenatal", "provider behavior", "reproductive epidemiology", "substance use", "therapy design", "therapy development", "usability" ], "approved": true } }, { "type": "Grant", "id": "15804", "attributes": { "award_id": "1R01AI187899-01A1", "title": "Optimizing lipid RVn monophosphate prodrugs to maximize RVn-triphosphate delivery", "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": 32536, "first_name": "DIPANWITA", "last_name": "BASU", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-18", "end_date": "2029-06-30", "award_amount": 3082513, "principal_investigator": { "id": 32895, "first_name": "Aaron F.", "last_name": "Carlin", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2637, "ror": "", "name": "UNIVERSITY OF CALIFORNIA, SAN DIEGO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Emerging RNA viruses, especially respiratory viruses, are among the leading threats to global health. With few treatments currently available, there is an urgent and ongoing need for the development of safe, effective oral antivirals. The objective of this application is to optimize an innovative lipid prodrug delivery strategy for remdesivir nucleoside monophosphate (RVn-MP), and additional broad-spectrum nucleoside antivirals, to achieve 1) excellent oral bioavailability, 2) efficient intracellular activation across tissue types, and 3) bypass of liver metabolism to enhance tissue delivery. The central hypothesis is that specific modifications to the lipid prodrug scaffold can improve in vivo antiviral efficacy by enhancing prodrug metabolism to the active metabolite and augmenting tissue delivery. The rationale for this project is that a better understanding of how lipid prodrug modifications increase antiviral activity will allow for the rational design and development of novel broad- spectrum oral antivirals for the treatment of clinically important RNA viruses. Strategy: Aim 1 will identify the mechanisms that determine prodrug antiviral potency in vitro to maximize antiviral activity. Quantitation of lipid RVn-MP prodrugs and their metabolites in cell culture using mass spectrometry will determine how scaffold modifications alter uptake, metabolism, and antiviral activity. Genetic knockout studies will identify the specific phospholipase C (PLC) enzyme/s that are necessary for lipid RVn-MP prodrug metabolism across cell types. Finally, PLC enzyme kinetic studies will identify scaffold modifications that maximize metabolism and antiviral activity in vitro. These data will inform lipid prodrug scaffold design that optimizes lipid RVn-MP potency. Aim 2 will determine how lipid prodrug modifications control distribution to maximize tissue delivery. First-pass removal of oral drugs by the liver is a common problem in drug development. We will evaluate how oral lipid nucleoside prodrugs can partition into chylomicrons, move through lymphatics to the thoracic duct, and thereby avoid first-pass liver metabolism while increasing lung delivery. Structure-activity relationship studies using a library of lipid RVn prodrugs will identify scaffold modifications that increase intestinal lymphatic trafficking and improve serum pharmacokinetics and tissue distribution. Scaffolds that maximize in vitro antiviral activity (Aim 1) and in vivo lung delivery (Aim 2) will be selected to rationally design new lipid RVn- MP prodrugs and novel lipid prodrugs containing nucleosides with broad spectrum activity against RNA viruses. New compounds will be evaluated for increased metabolism and antiviral activity in vitro, tissue delivery in vivo, and efficacy against pathogenic coronaviruses and dengue in mice. Collectively, this proposal will optimize the antiviral efficacy of oral lipid RVn-MP prodrugs for the treatment of many clinically important RNA viruses. Additionally, a better understanding of how to maximize the efficacy of lipid nucleoside prodrug design may be the key to unlocking a whole new generation of broad-spectrum antivirals.", "keywords": [ "2019-nCoV", "Affect", "Anti-viral Agents", "Biological Availability", "Bypass", "COVID-19 treatment", "Cell Culture Techniques", "Chylomicrons", "Clinical", "Clinical Treatment", "Coronavirus", "Data", "Dengue", "Dengue Virus", "Development", "Drug Kinetics", "Drug or chemical Tissue Distribution", "Ebola", "Enzyme Kinetics", "Enzymes", "Esters", "Excision", "Filovirus", "Flavivirus", "GS-441524", "Generations", "Genetic", "Glycerol", "In Vitro", "Intestines", "Knock-out", "Libraries", "Lipids", "Liver", "Lung", "Lymphatic", "Lysophospholipids", "Marburgvirus", "Mass Spectrum Analysis", "Metabolic", "Metabolism", "Methods", "Mission", "Modification", "Mus", "National Institute of Allergy and Infectious Disease", "Nipah", "Nucleosides", "Oral", "Oral Administration", "Paramyxovirus", "Pathogenicity", "Pharmaceutical Preparations", "Phospholipase C", "Plasma", "Positioning Attribute", "Prodrugs", "Public Health", "Publishing", "RNA Virus Infections", "RNA Viruses", "RNA-Directed RNA Polymerase", "Series", "Serum", "Site", "Small Intestines", "Structure-Activity Relationship", "Synthesis Chemistry", "Therapeutic", "Thoracic Duct", "Tissues", "Viral", "Viral Physiology", "Virus", "Virus Replication", "absorption", "analog", "anti-viral efficacy", "cell type", "design", "drug development", "esterase", "global health", "improved", "in vitro activity", "in vivo", "innovation", "lipophilicity", "liver metabolism", "mouse model", "novel", "nucleoside monophosphate", "pandemic potential", "preclinical efficacy", "rational design", "remdesivir", "respiratory virus", "scaffold", "targeted delivery", "trafficking", "tripolyphosphate", "uptake" ], "approved": true } }, { "type": "Grant", "id": "15803", "attributes": { "award_id": "1I01HX003797-01A3", "title": "Evaluating Veterans' Reproductive Healthcare Access, Quality and Outcomes in a Changing Landscape (EVOLVE)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2025-07-01", "end_date": "2029-06-30", "award_amount": null, "principal_investigator": { "id": 32893, "first_name": "Lisa Susanne", "last_name": "Callegari", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32894, "first_name": "Deirdre A", "last_name": "Quinn", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2660, "ror": "", "name": "VA PUGET SOUND HEALTHCARE SYSTEM", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Background: Recent years have witnessed unprecedented changes in the reproductive healthcare landscape in the US, including heightened awareness of reproductive health inequities following the 2020 nationwide racial justice reckoning, barriers to access resulting from the COVID-19 pandemic, and the proliferation of state abortion restrictions and bans following the 2022 Dobbs v Jackson Supreme Court decision. Today, access to high-quality, equitable contraceptive care has never been more vital for Veterans, who face elevated risks of poor outcomes from unintended pregnancy due to high rates of health comorbidities and psychosocial risks. The Examining Contraceptive Use and Unmet Need in Veterans (ECUUN) survey fielded in 2014-16 by study team members demonstrated high rates of unintended pregnancy and gaps in VA contraceptive access and quality, with significant disparities among Black and Latinx Veterans. While the ECUUN study helped inform VA’s reproductive health policies to date, updated data are urgently needed to capture VA’s progress in addressing disparities over time as well as its ability to meet Veterans’ needs in today’s shifted landscape. Significance: This study will generate timely quantitative and qualitative data necessary for VA as a learning health system to address gaps in access and quality and to adapt its policies and programming to meet Veterans’ changing needs. In addition, this study focuses on contraceptive counseling experiences in marginalized Veterans, for whom this care may be fraught due to the US history of reproductive oppression such as forced sterilization and policies to punish or limit reproduction in racial minority and low-income people. Findings will enable VA to respond to new White House and congressional directives related to women’s health that call for research to advance reproductive healthcare access and reduce disparities in care. Innovation & Impact: This proposal is innovative in its timeliness, use of prior data to draw novel comparisons over time, deployment of new state-of-the-art person-centered measures not yet fielded in VA such as the National Quality Forum (NQF)-endorsed Person-Centered Contraceptive Counseling (PCCC) measure, and collection of data to capture experiences of VA’s new policy to provide abortion care in select cases. Specific Aims: Aim 1: To use quantitative survey data to examine changes over time since ECUUN in contraceptive use, unintended pregnancy, and abortion, including differences by Veteran characteristics (e.g., race/ethnicity, geography). Aim 2: To use quantitative survey data to test for current disparities in novel person-centered measures (e.g., PCCC) by Veteran characteristics and characteristics of their health care. Aim 3: To contextualize Aim 1 & 2 findings, including disparities in experiences of contraceptive care and unintended pregnancy/abortion, by conducting qualitative interviews with Veterans. Methodology: This is a sequential explanatory mixed methods study beginning with a national survey of 3,600 pregnancy-capable reproductive-age Veterans who used VA primary or gynecology care in the past year. Qualitative interviews will then be conducted among Veteran survey respondents, purposively sampling at-risk subgroups (Black, Latinx, rural, residence in abortion-restrictive state) whose survey responses indicate gaps in care quality or equity. Quantitative data will inform qualitative sampling and data collection, and quantitative and qualitative data will be integrated using mixed methods analytic techniques including joint displays. Next Steps/Implementation: Next steps will include conducting a stakeholder engagement meeting with Veterans, women’s health providers, and operational partners from the Offices of Women’s Health, Health Equity, and Rural Health to share key research findings, develop strategic goals, and prioritize interventions to address disparities in contraceptive access and quality. Ultimately, this study has the potential to enhance VA’s ability to be a national leader in delivering high-quality and person-centered reproductive healthcare and to inform efforts to advance quality and equity in reproductive healthcare both within and beyond the VA.", "keywords": [ "Address", "Awareness", "Black race", "COVID-19 pandemic", "Caring", "Characteristics", "Clinic", "Clinical", "Coercion", "Collaborations", "Congresses", "Constitution", "Contraceptive Agents", "Contraceptive Usage", "Contraceptive methods", "Counseling", "Data", "Data Collection", "Development", "Disparity", "Equity", "Ethnic Origin", "Exclusion", "Female", "Geography", "Goals", "Gynecology", "Health", "Health Care", "Health Personnel", "Health Policy", "Health system", "Individual", "Intention", "Intervention", "Interview", "Investments", "Involuntary Sterilization", "Joints", "Judgment", "Justice", "Latina", "Latinx", "Lead", "Learning", "Low Income Population", "Low income", "Measures", "Medical", "Medical Records", "Mental Health", "Methodology", "Methods", "Mission", "Movement", "Outcome", "Personal Satisfaction", "Persons", "Policies", "Populations at Risk", "Pregnancy", "Proliferating", "Provider", "Punishment", "Quality of Care", "Race", "Recording of previous events", "Reproduction", "Reproductive Health", "Reproductive History", "Research", "Respondent", "Risk", "Rural", "Rural Health", "Sampling", "Services", "Subgroup", "Supreme Court Decisions", "Surveys", "Techniques", "Testing", "Time", "Trust", "United States Department of Veterans Affairs", "Update", "Veterans", "Voice", "Women's Health", "abortion", "access disparities", "analytical method", "comorbidity", "disparity reduction", "experience", "field survey", "gaps in access", "gender minority group", "health care availability", "health care disparity", "health care settings", "health equity", "health inequalities", "innovation", "marginalization", "marginalized population", "medical vulnerability", "meetings", "member", "novel", "patient oriented", "people of color", "person centered", "preference", "pregnancy related death", "prevent", "primary care provider", "psychosocial", "racial disparity", "racial minority", "reproductive", "reproductive age", "residence", "response", "rural area", "rurality", "sample collection", "sexual minority group", "sexual trauma", "social", "unintended pregnancy" ], "approved": true } }, { "type": "Grant", "id": "15800", "attributes": { "award_id": "1F31AI191669-01", "title": "Uncovering the mechanisms and implications of BST2 antagonism by SARS-CoV-2", "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": 32891, "first_name": "MARY KATHERINE BRADFORD", "last_name": "PLIMACK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-01", "end_date": "2028-06-30", "award_amount": 49538, "principal_investigator": { "id": 32892, "first_name": "Haley", "last_name": "Aull", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2634, "ror": "", "name": "UNIVERSITY OF ROCHESTER", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "BST2/Tetherin is a key factor of the cellular intrinsic immune response that broadly restricts enveloped viruses. BST2 tethers nascent virions to the cell surface by embedding itself into cellular and viral membranes. Tethering not only limits viral release, but also facilitates adaptive immune recognition of the infecting virus. Tethered virions are opsonized by antibodies, which can be recognized by Fc receptors on both natural killer cells and macrophages, activating their ability to kill or phagocytose the infected cell. We have recently reported that SARS-CoV-2 is susceptible to BST2 restriction. However, the virus has evolved to use its Spike to downregulate BST2. Downregulation is achieved by an interaction between Spike and the extracellular domains of BST2, routing BST2 for lysosomal degradation in a Clathrin- and Ubiquitin-dependent manner. Remarkably, newly emerged variants of concern (VOC) have enhanced their ability to counteract BST2, suggesting that BST2 antagonism is a contributing factor to the host adaptation of SARS-CoV-2. Therefore, my long-term goal is to block the ability of SARS-CoV-2 to evade BST2 restriction. My overall objective is to understand the mechanism and implications of BST2 evasion by SARS-CoV-2. My central hypothesis is that mutations accumulated in the Spike of SARS-CoV-2 allow for more efficient counteraction of BST2, increasing virion release and reducing the susceptibility of SARS-CoV-2 to BST2-dependent antibody-mediated cellular responses. I will achieve my overall objective by exploring these two specific aims: (1) elucidate the mechanism of enhancement of BST2 antagonism across VOC, and (2) identify the driving pressures of BST2 antagonism. This work is significant as it will (1) fill the critical gap in knowledge of how SARS-CoV-2 evades BST2 restriction, and how VOC enhance this activity; (2) define the extent to which evasion of BST2 allows for evasion of antibody-mediated responses, and how this translates to vaccine efficacy; and (3) provide proof-of-concept for the design of antivirals to disable SARS-CoV- 2 antagonism of BST2 with the goal of both blocking viral replication and enhancing clearance of infected cells. The support provided by this F31 award will enhance my education by (1) facilitating my training in Surface Plasmon Resonance by Dr. Jermaine Jenkins and the URMC Structural Biology Core Facility (see letter of support), (2) allowing me to travel to the University of Wisconsin-Madison to gain hands-on training from my co- sponsor, Dr. David Evans (see co-sponsor statement), who developed assays to measure Fc receptor-mediated killing of infected cells, which we are proposing to use here, and (3) expanding my experience in scientific writing and communication as I publish my findings and present at both national and international conferences.", "keywords": [ "2019-nCoV", "Affinity", "Anti-viral Agents", "Antibodies", "Antibody-Dependent Enhancement", "Automobile Driving", "Award", "Binding", "Biological Assay", "COVID-19 susceptibility", "COVID-19 vaccine", "Cell surface", "Cells", "Clathrin", "Collaborations", "Communication", "Core Facility", "Coronavirus", "Defect", "Down-Regulation", "Education", "Extracellular Domain", "Fc Receptor", "Future", "Goals", "Immune", "Immune response", "Immunoprecipitation", "International", "Knowledge", "Letters", "Macrophage", "Maps", "Measures", "Mediating", "Membrane", "Mutation", "Natural Killer Cells", "Predisposition", "Process", "Proteins", "Publications", "Publishing", "Reporting", "Resistance", "Role", "Route", "SARS-CoV-2 B.1.1.529", "SARS-CoV-2 antibody", "Surface Plasmon Resonance", "Susceptibility Gene", "Testing", "Training", "Translating", "Travel", "Ubiquitin", "Universities", "Vaccine Design", "Viral", "Virion", "Virus", "Virus Replication", "Wisconsin", "Work", "Writing", "antagonist", "antibody-dependent cell cytotoxicity", "antibody-dependent cellular phagocytosis", "base", "design", "experience", "improved", "pressure", "response", "skills", "structural biology", "symposium", "vaccine efficacy", "variants of concern" ], "approved": true } }, { "type": "Grant", "id": "15799", "attributes": { "award_id": "1R43CA298267-01A1", "title": "Ultra-precision diagnostics for ALK+ non-small cell lung cancer", "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": 32888, "first_name": "SWAMY KRISHNA", "last_name": "TRIPURANI", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-09", "end_date": "2026-06-30", "award_amount": 399153, "principal_investigator": { "id": 32889, "first_name": "David Randall", "last_name": "Armant", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32890, "first_name": "Rodrigo C", "last_name": "Fernandez-Valdivia", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2658, "ror": "", "name": "ALELOPHARMA INC.", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Background & Significance: Identifying ALK-positive lesions, which are highly responsive to treatment with Crizotinib or Alectinib, is a high-priority for managing patients with ALK+ Non-Small Cell Lung Cancer (NSCLC). A blood-based companion diagnostic (liquid biopsy) could monitor NSCLC patients post-treatment for tumor recurrence without tissue re-biopsy, and also identify non-symptomatic ALK+ individuals for earlier, more effective treatment with ALK kinase inhibitors. Expansion of this approach to other major oncogenic mutations has potential as a non-invasive cancer screening tool that would be transformative for healthcare. Objective & Innovation: AleloPharma Inc. is achieving solutions for personalized precision medicine using AleloMAX, an innnovative high-dimensional molecular detection system that allows ultra-specific detection of target nucleic acids with an impressive 1-absolute copy per reacting assay limit-of-detection (LOD) that effectively eliminates both false positives and false negatives. We aim to offer clinicians a cutting-edge diagnostic capable of accurately detecting ALK translocations among cell-free RNA in the blood plasma of affected patients. Approach: A proof-of-principle study, supported by preliminary LOD data obtained with synthetic ALK constructs, is proposed to develop a liquid biopsy test to detect ALK translocation variants in a kit for use in clinical labs. • Specific Aim 1: Develop an ultra-specific and ultra-sensitive molecular detection platform for EML4-ALK gene fusion translocations in ALK+ NSCLC. We will probe EML4-ALK fusion RNAs using synthetic, in vitro-transcribed mRNAs encompassing the distinct EML4-ALK oncogenic variants. • Specific Aim 2: Demonstrate AleloMAX-ALK’s superior resolution power in ultra-specific molecular probing and limit-of-detection (LOD) analysis in a clinical proof-of-principle study. The EML4-ALK diagnostic platform will be tested using plasma- and/or blood-derived nucleic acid samples obtained from ALK+ NSCLC patients, ALK- NSCLC patients, and healthy control volunteers. Team & Commercialization: Led by a distinguished team with a track record of groundbreaking research in molecular pharmacology, oncology and cellular biology, we are uniquely positioned to tackle this challenge. Our clear roadmap includes patenting all IP and aspires to launch a diagnostic that will have significant clinical utility. Feasibility & Impact: The assay is expected to detect low levels of EML4-ALK mutations in blood of individuals with ALK+ NSCLC. AleloMAX demonstrated diagnostic superiority in prior studies of the NSCLC biomarker POGLUT-1, SARS-CoV-2 and RSV with impressive results. Assay parameters established in this project will be developed as a kit for use in a Phase II study to establish its clinical utility as a companion diagnostic for NSCLC. Successful development of an ALK+ cancer diagnostic will be expanded to include assays for RET, ROS1 and other onco-mutations with additional AleloMAX liquid biopsy assays to monitor a broader panel of cancers. Conclusion: Combining innovation and tangible clinical benefit, our initiative represents a transformative shift in early detection and management of cancer that will positively impact patient survival.", "keywords": [ "2019-nCoV", "ALK gene", "Acceleration", "Address", "Affect", "Aftercare", "Algorithms", "Archives", "Award", "Biological Assay", "Biopsy", "Blood", "Businesses", "COVID-19 diagnosis", "Cancer Detection", "Cancer Diagnostics", "Cancer Patient", "Cells", "Cellular biology", "Chemistry", "Chromosomal translocation", "Clinical", "DNA Sequence Alteration", "Data", "Detection", "Development", "Diagnosis", "Diagnostic", "Diagnostic tests", "Disease", "Early Diagnosis", "Evaluation", "Event", "Fluorescent in Situ Hybridization", "Future", "Gene Amplification", "Gene Fusion", "Genetic Transcription", "Health Care", "Image", "In Vitro", "Individual", "Industry", "Legal patent", "Lesion", "Malignant Neoplasms", "Malignant neoplasm of lung", "Marketing", "Methods", "Molecular", "Molecular Genetics", "Molecular Probes", "Monitor", "Mutation", "Neoplasms", "Non-Small-Cell Lung Carcinoma", "Nucleic Acids", "Oncogenes", "Oncogenic", "Oncology", "Patient Monitoring", "Patients", "Performance", "Pharmacology", "Phase", "Plasma", "Positioning Attribute", "Probability", "Procedures", "Process", "Prognosis", "Protein Tyrosine Kinase", "RNA", "ROS1 gene", "Reaction", "Recurrent tumor", "Research", "Resolution", "Sampling", "Screening for cancer", "Screening procedure", "Sensitivity and Specificity", "Series", "Signal Transduction", "Specificity", "Techniques", "Technology", "Testing", "Therapeutic", "Therapeutic Intervention", "Time", "Tissues", "Transcript", "Tube", "Tyrosine Kinase Inhibitor", "Variant", "Vision", "Work", "biobank", "cancer biomarkers", "cancer diagnosis", "chromosome fusion", "cohort", "commercialization", "companion diagnostics", "comparative", "crizotinib", "detection assay", "detection limit", "detection platform", "diagnostic platform", "diagnostic technologies", "diagnostic tool", "diagnostic value", "early screening", "effective intervention", "effective therapy", "genetic diagnostics", "high dimensionality", "improved", "inhibitor", "innovation", "kinase inhibitor", "liquid biopsy", "molecular diagnostics", "next generation", "next generation sequencing", "novel", "overexpression", "patient screening", "personalized diagnostics", "phase 2 study", "precision medicine", "screening", "sensor technology", "success", "tumor", "validation studies", "volunteer" ], "approved": true } }, { "type": "Grant", "id": "15798", "attributes": { "award_id": "1DP2AI192737-01", "title": "Decoding multidrug-resistant pathogen dynamics for clinically-relevant wastewater surveillance", "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": 32875, "first_name": "INKA I", "last_name": "SASTALLA", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-07-23", "end_date": "2030-06-30", "award_amount": 534000, "principal_investigator": { "id": 32887, "first_name": "Medini K", "last_name": "Annavajhala", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2657, "ror": "", "name": "CHILDREN'S HOSP OF PHILADELPHIA", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Multidrug-resistant bacteria (MDRB) contribute increasingly to morbidity, mortality, and healthcare costs. Extended-spectrum beta-lactam- and carbapenem-resistant Enterobacterales (ESBL-E and CRE) are MDRB of particular concern due to their demonstrated ability to evolve into highly transmissible clones and acquire and spread antibiotic resistance determinants. Traditional epidemiological surveillance typically focuses on outbreaks of MDRB causing clinical infections, underestimating the burden of these pathogens within hospital systems. Broader efforts that account for asymptomatic carriage and environmental and community reservoirs would be ideal to track and mitigate the spread of MDRB. Wastewater surveillance has proven an effective tool for public health pathogen monitoring, as shown with SARS-CoV-2, but has not been established in clinical settings. This proposal will develop new systems to leverage wastewater for clinically applicable, proactive, and readily deployable MDRB monitoring. In Aim 1, we will establish standardized longitudinal surveillance strategies to inform infection control responses. We will use long-read metagenomics and novel bioinformatic approaches to rapidly identify significant changes in relative or absolute abundance of ESBL-E or CRE compared to site-specific baselines. We will also establish methods to translate wastewater testing data into interpretable “action thresholds” for use by hospital and clinical teams. In Aim 2, we will identify factors enabling the emergence of novel ESBL-E and CRE genotypes in the wastewater environment. Wastewater sampling can identify novel resistant genotypes before detection of clinical infections. We will further develop our novel Metapore-C technique to link bacterial hosts with resistance gene-harboring mobile elements and will use this approach to identify environmental factors such as wastewater antibiotic levels and plumbing design associated with acquisition of resistance. Lastly, in Aim 3 we will devise wastewater testing methodologies suited to resource-limited clinical settings. Given the costs and infrastructure needed for comprehensive clinical surveillance, wastewater testing is better poised to aid in mitigation of MDRB under resource constraints. Yet, current wastewater surveillance approaches are often impractical in such settings. Our strategies for reducing per-sample costs and the analytical burden of wastewater data interpretation, as piloted at a pediatric hospital in Gaborone, Botswana, will serve as a proof-of-concept for wastewater MDRB testing in diverse contexts. Overall, this project will significantly broaden the ability of wastewater surveillance to inform hospital and clinical care efforts, while establishing best practices for global surveillance of antimicrobial resistance in hospital wastewater.", "keywords": [ "2019-nCoV", "Address", "Antibiotic Resistance", "Antibiotics", "Antimicrobial Resistance", "Bacterial Infections", "Bioinformatics", "Biological Testing", "Botswana", "COVID-19 pandemic", "Childhood", "Clinical", "Communities", "Complement", "Data", "Data Analyses", "Detection", "Development", "Disease Outbreaks", "Elements", "Enabling Factors", "Environment", "Environmental Risk Factor", "Epidemiologic Monitoring", "Epidemiology", "Genetic Materials", "Genomics", "Genotype", "Goals", "Health Care Costs", "Health Care Systems", "Horizontal Gene Transfer", "Hospitals", "Infection", "Infection Control", "Infection prevention", "Infrastructure", "Link", "Metagenomics", "Methodology", "Methods", "Mobile Genetic Elements", "Molecular", "Monitor", "Morbidity - disease rate", "Multi-Drug Resistance", "Outcome", "Patients", "Pediatric Hospitals", "Plasmids", "Plumbing", "Population", "Postdoctoral Fellow", "Prevalence", "Protocols documentation", "Public Health", "Research", "Resistance", "Resource-limited setting", "Resources", "Sampling", "Site", "Standardization", "System", "Techniques", "Testing", "Therapeutic", "Thinking", "Translating", "Treatment Failure", "United States", "Work", "beta-Lactams", "bioinformatics pipeline", "carbapenem resistant Enterobacterales", "clinical application", "clinical care", "clinical sequencing", "clinically relevant", "combat", "cost", "cost effective", "design", "experience", "health care settings", "hospital care", "improved", "innovation", "low and middle-income countries", "microbiome", "microbiota", "microorganism", "mortality", "multi-drug resistant bacteria", "multi-drug resistant pathogen", "novel", "pathogen", "resistance gene", "resistance mechanism", "response", "surveillance strategy", "tool", "wastewater sampling", "wastewater surveillance", "wastewater testing" ], "approved": true } }, { "type": "Grant", "id": "15797", "attributes": { "award_id": "1R01HL176849-01A1", "title": "Pathogenic mechanisms of chronic lung sequelae following respiratory viral infection", "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": 32514, "first_name": "EMMANUEL FRANCK", "last_name": "MONGODIN", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-10", "end_date": "2029-05-31", "award_amount": 754729, "principal_investigator": { "id": 32886, "first_name": "John F", "last_name": "Alcorn", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32525, "first_name": "Lianghui", "last_name": "Zhang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 848, "ror": "", "name": "UNIVERSITY OF PITTSBURGH AT PITTSBURGH", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic has brought the world’s attention on respiratory viral infections. It is not a question of if another respiratory viral pandemic will arise, but rather when. The diversity of viral pathogens presents a tremendous challenge for designing virus targeted preventions and therapeutics. However, respiratory viruses cause similar lung injury that drives morbidity and mortality. A focus on host mediated lung injury pathways in this context is warranted, as there is potential for therapeutic interventions that would be effective across a range of respiratory viral infections. The COVID-19 pandemic has drawn attention to a poorly characterized phenotype of persistent lung inflammation that lasts well beyond clearance of live virus. Long-COVID and long-Flu are clinical diagnoses that lack an understanding of the molecular underpinnings of disease. In this application, we focus on understanding the mechanism by which respiratory viral infection causes lasting tissue damage covering antigen persistence, presentation, and a positive feedback inflammatory cell network. We propose that the persistent presence of viral antigen in pulmonary endothelial cells is a major driver for the prolonged activation of CD8+ T cells, consequently leading to chronic pulmonary sequelae, through reinforced interaction of CD8+ TRM cells and pro-inflammatory macrophages. This hypothesis will be tested in two Aims: 1) we will investigate the contribution of persistent activation of CD8+ T cells by pulmonary endothelial cells to the development of chronic pulmonary sequelae, and 2) we will interrogate the T cell and macrophage inflammatory axis in persistent inflammation during recovery from respiratory viral infection. To examine these pathways, we will employ the SARS-CoV-2 and influenza virus mouse models, and we will confirm findings using tissue from human patient transbronchial biopsies. Discovery of causative host inflammatory pathways that are critical to post-viral lung sequelae would provide pre-clinical evidence to support clinical trials. If pathogenic mechanisms are indeed similar between multiple respiratory viruses, then host-directed therapeutics would potentially have a tremendous impact. Currently, there are no specific therapies indicated for the treatment of post-viral lung inflammation.", "keywords": [ "2019-nCoV", "Acute", "Antibodies", "Antigen Presentation", "Antigen-Presenting Cells", "Antigens", "Attention", "Automobile Driving", "Biopsy", "Biopsy Specimen", "CD8-Positive T-Lymphocytes", "CD8B1 gene", "COVID-19 pandemic", "Cells", "Chronic", "Clinical Trials", "Coronavirus Infections", "Critical Pathways", "Data", "Development", "Disease", "Economic Burden", "Endothelial Cells", "Endothelium", "Epidemic", "Exudate", "Feedback", "Fibrosis", "Frustration", "Functional disorder", "Goals", "Human", "IFNGR1 gene", "Immune", "In Vitro", "Infection", "Inflammation", "Inflammatory", "Influenza", "Influenza A Virus H1N1 Subtype", "Interferon Type II", "Intervention", "Knock-out", "Long COVID", "Lung", "Lymphocyte", "Lymphoid", "MHC Class I Genes", "Macrophage", "Mediating", "Metabolism", "Molecular", "Morbidity - disease rate", "Mus", "Myelogenous", "Pathogenesis", "Pathogenicity", "Pathologic", "Pathway interactions", "Patients", "Phenotype", "Population", "Post-Acute Sequelae of SARS-CoV-2 Infection", "Prevention", "Production", "Proteins", "Public Health", "Pulmonary Inflammation", "Recovery", "Resolution", "Role", "SARS-CoV-2 infection", "Signal Transduction", "Source", "T-Lymphocyte", "T-cell inflamed", "Testing", "Therapeutic", "Therapeutic Intervention", "Tissues", "Upper Respiratory Infections", "Viral", "Viral Antigens", "Viral Respiratory Tract Infection", "Virus", "Virus Diseases", "Work", "beta-2 Microglobulin", "clinical diagnosis", "coronavirus pandemic", "cytokine", "design", "effector T cell", "experience", "flu", "human tissue", "influenza infection", "influenzavirus", "lung injury", "lung microvascular endothelial cells", "lung repair", "mortality", "mouse model", "neutralizing antibody", "novel", "pathogenic virus", "pharmacologic", "polarized cell", "pre-clinical", "pulmonary", "pulmonary vascular cells", "repaired", "respiratory", "respiratory virus", "restoration", "single-cell RNA sequencing", "socioeconomics", "spatial transcriptomics", "tissue resident memory T cell", "viral pandemic" ], "approved": true } }, { "type": "Grant", "id": "15796", "attributes": { "award_id": "1R44NS145848-01", "title": "Development of Tissue Engineered Tregs as a Treatment for Acute Ischemic Stroke", "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": 32884, "first_name": "FLOY ANNETTE", "last_name": "GILCHRIST", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-15", "end_date": "2027-07-31", "award_amount": 1150417, "principal_investigator": { "id": 32885, "first_name": "Payam", "last_name": "Zarin", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2656, "ror": "", "name": "GENTIBIO, INC.", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "In the U.S., nearly 800,000 individuals experience a stroke each year, predominantly ischemic strokes. The economic burden of stroke is staggering, with projected stroke-related medical costs in the U.S. expected to surpass $94 billion by 2035. This underscores the urgent need for effective therapies to address this significant public health challenge. While the potential of regulatory T cells (Tregs) in promoting stroke recovery has been recognized, translating this promise into clinical success has been hampered by several obstacles. Traditional Treg therapies face challenges in manufacturing, phenotypic instability, and a lack of tissue specificity. This proposal focuses on the development of allogeneic engineered tissue Tregs (EngTregs) as a novel off-the-shelf therapeutic approach for stroke. Overexpression of ST2, the receptor for the alarmin IL-33, enhances the ability of EngTregs to: (i) sense and respond to tissue damage (ST2-expressing EngTregs efficiently migrate to sites of inflammation and injury); (ii) suppress excessive inflammation (EngTregs exert potent anti-inflammatory effects through multiple mechanisms, including direct suppression of immune cells and modulation of the inflammatory environment); and (iii) actively participate in tissue repair (EngTregs produce growth factors and interact with other cells to promote tissue regeneration). Overexpression of FOXP3 ensures a stable and suppressive Treg phenotype, crucial for long-term therapeutic efficacy. A chemically induced signaling complex (CISC) enables tunable IL-2 signaling, promoting Treg survival and function while facilitating scalable manufacturing. These innovations culminate in a first-in-class allogeneic tissue EngTreg product with advantages in manufacturing scalability, cost-effectiveness, and therapeutic potential compared to conventional Treg therapies. Preliminary studies demonstrate the ability of allogeneic EngTregs to accumulate in the injured brain and improve motor skills, sensory function, learning, and memory following ischemic injury induced in the transient middle cerebral artery occlusion (tMCAO) mouse model of stroke. This proposal outlines three aims to further advance the preclinical development of EngTregs for stroke: Aim 1: Evaluate the therapeutic efficacy of EngTregs in two preclinical stroke models (permanent middle cerebral artery occlusion and photothrombosis) in both adult and aged mice, assessing a comprehensive range of functional and histological outcomes. Aim 2: Characterize the mechanism of action and define a comprehensive in vitro profile of the human EngTreg drug product, including assessment of cytokine sequestration, T cell suppression, macrophage polarization, and transcriptomic analysis. Aim 3: Assess the immunotoxicity and immunogenicity of human EngTregs to ensure clinical safety, including evaluation of cytokine release syndrome and allo-immunogenicity. Successful completion of these aims will provide critical preclinical data supporting the clinical translation of EngTregs as a novel and promising therapeutic strategy for stroke, addressing a significant unmet medical need.", "keywords": [ "AREG gene", "Acute", "Address", "Adhesives", "Adult", "Age", "Allogenic", "Antiinflammatory Effect", "Area", "Autologous", "Biological Assay", "Blood flow", "Brain Injuries", "C57BL/6 Mouse", "CCR5 gene", "CCR8 gene", "Cell Physiology", "Cell Survival", "Cell Therapy", "Cells", "Cessation of life", "Characteristics", "Chemicals", "Clinical", "Clinical Data", "Cognitive", "Complex", "Development", "Economic Burden", "Engraftment", "Ensure", "Evaluation", "FOXP3 gene", "Face", "Female", "Flow Cytometry", "Growth Factor", "Guidelines", "Health Care Systems", "High Prevalence", "Histologic", "Homing", "Human Engineering", "IL2RA gene", "Immune Cell Suppression", "In Vitro", "Individual", "Infarction", "Inflammation", "Inflammatory", "Injury", "Interleukin-13", "Interleukin-2", "Ischemic Stroke", "Learning", "Macrophage", "Mediating", "Medical", "Medical Care Costs", "Memory", "Middle Cerebral Artery Occlusion", "Mixed Lymphocyte Culture Test", "Modeling", "Motor Skills", "Mus", "Outcome", "Outcome Measure", "Patient-Focused Outcomes", "Patients", "Performance", "Persons", "Pharmaceutical Preparations", "Phase", "Phenotype", "Preclinical data", "Process", "Public Health", "Receptors Tumor Necrosis Factor Type II", "Recovery of Function", "Regulatory T-Lymphocyte", "Reperfusion Therapy", "Research", "Risk", "Safety", "Sensory", "Signal Induction", "Signal Transduction", "Sirolimus", "Site", "Specificity", "Stroke", "T cell therapy", "T-Lymphocyte", "TNFRSF1B gene", "Testing", "Therapeutic", "Tissue Engineering", "Tissues", "Toxic effect", "Translating", "Treatment Efficacy", "Upregulation", "Work", "aged", "angiogenesis", "axon injury", "blood-brain barrier permeabilization", "brain repair", "clinical translation", "cost", "cost effectiveness", "cytokine", "cytokine release syndrome", "disability", "disease heterogeneity", "effective therapy", "experience", "foot", "human tissue", "immunogenicity", "immunotoxicity", "improved", "inflammatory milieu", "inflammatory modulation", "innovation", "ischemic injury", "male", "manufacture", "manufacturing process", "migration", "morris water maze", "mortality", "mouse model", "neurogenesis", "novel", "object recognition", "old mice", "osteopontin", "overexpression", "patient subsets", "post stroke", "pre-clinical", "preclinical development", "preclinical evaluation", "programs", "public health relevance", "receptor", "repaired", "stroke model", "stroke recovery", "stro" ], "approved": true } }, { "type": "Grant", "id": "15795", "attributes": { "award_id": "1R21EB037846-01", "title": "Design principles for engineering therapeutic macrophages", "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": 32882, "first_name": "TUBA HALISE", "last_name": "FEHR", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2028-07-31", "award_amount": 621158, "principal_investigator": { "id": 32883, "first_name": "Jason Hung-Ying", "last_name": "Yang", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2655, "ror": "", "name": "RUTGERS BIOMEDICAL AND HEALTH SCIENCES", "address": "", "city": "", "state": "NJ", "zip": "", "country": "United States", "approved": true }, "abstract": "Genetically engineered immune cells are an exciting and promising frontier for treating a wide range of complex diseases. However, hyperinflammatory toxicities such as cytokine release syndrome plague clinical trials, stymieing their widespread clinical adoption. Macrophages are innate immune cells that fulfill many roles in tissue repair, regeneration, and homeostasis and are important regulators of inflammation. However, they are significantly under-utilized as engineered immune cell therapies because significant knowledge gaps exist in understanding how to engineer synthetic gene circuits that work robustly in human macrophages. Tools do not yet exist for determining how macrophages should be biologically manipulated to activate desired effector functions (biological design principles). Tools also do not exist for determining what gene circuit architectures are needed to robustly induce desired gene circuit behaviors (gene circuit design principles). The overall goal for this proposal is to create a human macrophage design toolkit for engineering therapeutic macrophages. Our published and preliminary data demonstrate that we have developed tools that enable us to discover cell signaling interventions that can control macrophage effector functions (biological design principles) and gene circuit architectures that can exert robust behaviors in human macrophages (gene circuit design principles). Here we will apply both these approaches to elucidate biological and gene circuit design principles that can be used to engineer therapeutic macrophages that can suppress inflammatory cytokine secretion or induce anti- inflammatory cytokine secretion in inflamed tissues. We will elucidate biological design principles using an interpretable machine learning approach that we previous developed. This approach combines biochemical screening with predictive network modeling and machine learning to discover network mechanisms causally regulating cell phenotypes. We will elucidate gene circuit design principles using a recently developed ultra-high- throughput genetic screening approach (CLASSIC). This approach synthesizes and screens large, barcoded gene circuit libraries to associate gene circuit architectures with gene circuit behaviors. With these design principles we will engineer gene circuits for controlling IL-1β or IL-10 secretion in inflamed tissue contexts and validate these synthetic gene circuits in human monocyte-derived macrophages and THP-1 cells. In its entirety, this Trailblazer R21 project is a first step towards addressing the unmet need for design principles for engineering therapeutic macrophages. We envision that insights gained by this project will help establish engineered macrophages as a platform technology for treating a wide range of complex human diseases.", "keywords": [ "Address", "Adoption", "Anti-Inflammatory Agents", "Architecture", "Bar Codes", "Behavior", "Biochemical", "Biological", "Cells", "Cellular immunotherapy", "Clinical", "Clinical Trials", "Complex", "Data", "Disease", "Engineered Gene", "Engineering", "Environment", "Future", "Genes", "Genetic", "Genetic Engineering", "Genetic Screening", "Goals", "Homeostasis", "Human", "Immune", "Inflammation", "Inflammatory", "Interleukin-1 beta", "Interleukin-10", "Intervention", "Knowledge", "Libraries", "Machine Learning", "Macrophage", "Natural regeneration", "Phenotype", "Plague", "Process", "Publishing", "Role", "Signal Transduction", "Synthetic Genes", "Therapeutic", "Tissues", "Toxic effect", "Work", "cytokine", "cytokine release syndrome", "design", "explainable machine learning", "frontier", "gene discovery", "human disease", "immunoengineering", "insight", "monocyte", "network models", "prototype", "screening", "simulation", "synthetic biology", "technology platform", "tissue repair", "tool" ], "approved": true } }, { "type": "Grant", "id": "15793", "attributes": { "award_id": "1R03AI188484-01A1", "title": "Establishing Human 2D and 3D Testicular Models to Elucidate Monkeypox Virus Tropism and Pathogenic Mechanisms in the Testes", "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": 32841, "first_name": "JANE M", "last_name": "KNISELY", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-01", "end_date": "2027-07-31", "award_amount": 156500, "principal_investigator": { "id": 32880, "first_name": "SAGUNA", "last_name": "VERMA", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2653, "ror": "", "name": "UNIVERSITY OF HAWAII AT MANOA", "address": "", "city": "", "state": "HI", "zip": "", "country": "United States", "approved": true }, "abstract": "One of the most important lessons learned from the recent global outbreak of the monkeypox virus, now called Mpox virus (MPXV, clade II), is the recognition that males are at a much higher risk for infection and higher occurrence of genital rash. Transmission via sexual contact is one of the main routes of virus spread. However, whether MPXV constitutes a sexually transmitted infection and can infect the male reproductive tract is still being debated, thus affecting the strategies to minimize transmission risk. Confirmed reports of MPXV shedding in seminal fluid for long after the clearance of viremia suggest the ability of MPXV to establish a productive infection in genitourinary organs. Poxviruses can also cause testicular complications, including azoospermia and seminiferous tubule atrophy. More recently, MPXV antigens have been detected in the testis of nonhuman primates both during the acute and convalescent stages, and the presence of testicular inflammation and necrosis in these macaques collectively suggests testis-tropism of MPXV, like Zika and Ebola viruses. However, direct evidence of MPXV infection in human testis is currently lacking, including cell targets of the virus and downstream consequences. Relevant human in vitro models are needed to characterize MPXV testicular infection. Human testis immune homeostasis is tightly governed by an elaborate communication network between different cells including testosterone-producing Leydig cells (LC) and Sertoli cells (SC) that form the blood-testis barrier (BTB). We recently established a 3D human testicular organoid (HTO) system comprised of undifferentiated spermatogonia cells, SC, LC, and peritubular myoid cells that closely recapitulates the cell diversity and function of the human testis to study Zika virus and SARS-CoV-2 infection. We have also established 2D cultures of primary SC, LC, and mixed seminiferous tubule cells and an in vitro BTB model to delineate cell-specific responses to viruses. Therefore, the goal of this study is to utilize our 2D and 3D testicular culture systems as an effective in vitro surrogate to model testicular infection of MPXV and understand downstream consequences. In Aim 1, we will assess MPXV infection in the 2D and 3D HTOs, identify cell targets, and characterize key infection pathologies, including cytopathic effects, antiviral response, and effect on BTB integrity. Aim 2 will utilize single-cell RNA sequencing to determine relative infectivity in each cell type and key pathways, including antiviral and inflammatory response, cell death, and spermatogenesis. Collective data will provide much-needed evidence of the testis as one of the target organs of MPXV replication after it is cleared from blood and skin lesions and lay the foundation for future in vivo studies of transmission via the sexual route. The knowledge of whether MPXV is a sexually transmitted infection is critical in providing clinical management and transmission guidelines, especially in men who have sex with men (MSM), an underrepresented group in biomedical research.", "keywords": [ "2019-nCoV", "3-Dimensional", "Acute", "Affect", "Androgens", "Anti-viral Response", "Antigens", "Area", "Atrophic", "Basic Science", "Biological Assay", "Biomedical Research", "Biomimetics", "Blood", "Blood-Testis Barrier", "CASP3 gene", "Cell Death", "Cell Differentiation process", "Cell Survival", "Cells", "Clinical", "Clinical Management", "Communication", "Data", "Development", "Discipline of Nursing", "Disease", "Disease Outbreaks", "Dissociation", "Ebola virus", "Electrical Resistance", "Environment", "Exanthema", "Foundations", "Future", "Genitalia", "Genitourinary system", "Germ Cells", "Goals", "Guidelines", "Homeostasis", "Human", "Immune", "Impairment", "In Situ Nick-End Labeling", "In Vitro", "Individual", "Infection", "Inflammation", "Inflammatory Response", "Injury", "Interferons", "International", "Investigation", "Kinetics", "Knowledge", "Macaca", "Measures", "Modeling", "Monkeypox", "Monkeypox virus", "Necrosis", "Organ", "Organoids", "Pathogenesis", "Pathogenicity", "Pathology", "Pathway interactions", "Plaque Assay", "Poxviridae", "Productivity", "Public Health", "Reporting", "Research Personnel", "Risk", "Route", "SARS-CoV-2 infection", "Seminal fluid", "Seminiferous tubule structure", "Sexual Transmission", "Sexually Transmitted Diseases", "Skin", "Spermatogenesis", "Supporting Cell", "Surface", "Suspensions", "System", "Testing", "Testis", "Testosterone", "Time", "Tropism", "Tubular formation", "Underrepresented Populations", "Undifferentiated", "United States National Institutes of Health", "Viral", "Viral Pathogenesis", "Viremia", "Virus", "Virus Diseases", "Virus Replication", "ZIKA", "Zika Virus", "cell type", "effective therapy", "high risk", "high risk population", "human model", "in vitro Model", "in vivo", "infection risk", "insight", "leydig interstitial cell", "male", "men", "men who have sex with men", "migration", "multidisciplinary", "nonhuman primate", "novel", "novel therapeutics", "public health emergency", "receptor", "reproductive tract", "response", "sertoli cell", "single-cell RNA sequencing", "skin lesion", "spermatogonial stem cells", "therapeutic development", "three-dimensional modeling", "transmission process", "viral transmission", "virus tropism" ], "approved": true } } ], "meta": { "pagination": { "page": 1, "pages": 1405, "count": 14046 } } }