Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1405&sort=start_date
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=start_date", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1419&sort=start_date", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1406&sort=start_date", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1404&sort=start_date" }, "data": [ { "type": "Grant", "id": "15787", "attributes": { "award_id": "1R13HD118735-01", "title": "Health, Mortality, & Aging Among People with Criminal Legal System Contact in America", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 32868, "first_name": "RANDOLPH CHRISTOPHER", "last_name": "CAPPS", "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": 10000, "principal_investigator": { "id": 32869, "first_name": "Sade", "last_name": "Lindsay", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32870, "first_name": "Bryan Lamont", "last_name": "Sykes", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2650, "ror": "", "name": "CORNELL UNIVERSITY", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT SUMMARY/ABSTRACT: Criminal justice contact is an important contributor to population variation in health outcomes, including mortality, morbidity, and aging. During and following the COVID-19 pandemic, people in American jails, prisons, and detention centers experienced elevated health risks that exacerbated their already high morality and aging precariousness. This proposal requests support for a three-year conference program on, “Health, Mortality, and Aging Among People with Criminal Legal System Contact in America,” with each year focusing on critical questions about the health of incarcerated people that have emerged since the COVID-19 crisis. These interdisciplinary conferences will harness the research and expertise of established and emerging scholars conducting research at the intersections of health, mortality, and aging in economics, sociology, demography/population science, law, criminology, public health, medicine, and public policy. The proposed conference programs are innovative by including the participation of people affected by legal system involvement, as well as by investigating population heterogeneity to formulate and to advance a bold new research agenda that will benefit affected communities. The program has four specific aims: (1) to advance scientific knowledge and research recommendations to improve health across the life-course for people involved in the criminal legal system; (2) to amplify the voices of affected people, families, and communities; (3) to train the next generation of criminal legal scholars; and (4) to engage multiple audiences. Deliverables will include: (1) three special issues, each devoted to a unique conference theme over the three years (i.e., mortality, health, and aging), allowing for the discrete and unique treatment of each topic; and (2) research briefs that translate findings into potential interventions and recommendations that broadly engage the individuals, families, and communities subject to criminal justice contact, as well as other stakeholders (government officials, prison and court actors, non-profits, and other advocates). By discussing and documenting how life-course transitions that intersect with the criminal legal system matter for socio-economic, health, and well-being, this conference will engage and advance the conceptual and empirical dialogues that began with several National Academies of Sciences, Engineering, and Medicine workshops in 2013 and 2020, and, more recently, a half-day seminar in 2024. As leaders in the criminal legal field, the investigative team and Cornell University are uniquely positioned to host this program.", "keywords": [ "Acute", "Advocate", "Affect", "Aging", "American", "Area", "Attention", "COVID-19 pandemic", "Cessation of life", "Chronic", "Collaborations", "Collection", "Communities", "Community Health", "Consumption", "Correctional Institutions", "Criminal Justice", "Criminology", "Data", "Dedications", "Demography", "Development", "Economics", "Educational workshop", "Engineering", "Epidemiology", "Event", "Exclusion", "Exposure to", "Family", "Government Officials", "Health", "Imprisonment", "Individual", "Intervention", "Jail", "Journals", "Knowledge", "Laws", "Legal", "Legal system", "Life Cycle Stages", "Life Expectancy", "Lived experience", "Measures", "Medicine", "Mentors", "Methodology", "Methods", "Morality", "Morbidity - disease rate", "Outcome", "Participant", "Personal Satisfaction", "Persons", "Population", "Population Heterogeneity", "Population Sciences", "Positioning Attribute", "Prisons", "Public Health", "Public Policy", "Recommendation", "Reporting", "Request for Proposals", "Research", "Research Personnel", "Risk", "Scientific Advances and Accomplishments", "Scientific Inquiry", "Social Sciences", "Sociology", "Training", "Translating", "Translational Research", "United States National Academy of Sciences", "Universities", "Variant", "Voice", "career", "court", "detention center", "experience", "forging", "health difference", "improved", "improved outcome", "individualized medicine", "innovation", "labor market", "life span", "mortality", "next generation", "population health", "prison population", "programs", "public health relevance", "research and development", "socioeconomics", "symposium", "theories" ], "approved": true } }, { "type": "Grant", "id": "15791", "attributes": { "award_id": "1R21AI186055-01A1", "title": "UTS-1401: A Novel Mitigator of Radiation Injury", "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": 32876, "first_name": "ANDREA L", "last_name": "DICARLO-COHEN", "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": 431750, "principal_investigator": { "id": 32877, "first_name": "Stephen L", "last_name": "Brown", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 32878, "first_name": "FREDERICK Augustus", "last_name": "VALERIOTE", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2633, "ror": "", "name": "HENRY FORD HEALTH + MICHIGAN STATE UNIVERSITY HEALTH SCIENCES", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "Abstract: Our long term objective is to develop a new class of radiation mitigating agents with attractive chemical, physical and biological characteristics required to be an effective drug that can be distributed widely. We have identified a small molecule, UTS-1401 [5-(methylthiomethyl) isoxazole-3-carboxylic acid] which demonstrates mitigation of hematopoietic stem cell death when administered at either 24h or 48h following whole body irradiation (WBI). Using the endogenous spleen colony assay we demonstrated a significant mitigating effect (ratio of colony number with and without UTS-1401) when drug was given 24h or 48h after radiation. We have also recently demonstrated a significant radioprotection for both mouse survival and hematopoietic stem cells for this compound for up to 72h before irradiation (Valeriote et al, Radiation Research, 202:16-25, 2024). In this application, we propose to examine solely the mitigating effect to both the hematopoietic acute radiation syndrome (H-ARS) in specific aim 1 and the gastrointestinal acute radiation syndrome (GI-ARS) in specific aim 2 following WBI (with 5% bone marrow protection for specific aim 2). Swiss mice will receive a series of graded doses of WBI around the LD50 for both syndromes with and without the administration of 150 mg/kg UTS- 1401. The single dose of UTS-1401 being used in all studies is the highest dose administrable due to its aqueous solubility (in tartrate buffered saline). The radiation mitigation factors will be calculated as the ratio of the LD50 for radiation plus UTS-1401 versus radiation alone. The degree of mitigation will be examined at 24, 48 and 72 h following WBI to determine the timeframe of mitigation after radiation exposure. Three routes of drug delivery, intravenous (iv), oral, and subcutaneous (sc), will be examined and compared. For all specific aims, both male and female mice will be separately studied. Radiation will be delivered by electrons from a Linac. In specific aim 3, we will examine the pharmacokinetics (PK) for 150 mg/kg UTS-1401 comparing the iv, oral, and sc routes to obtain a determination of both the drug kinetics and bioavailability. The AUC values will be correlated with the extent of mitigation. Finally, in specific aim 4, we will address the mechanism of action with studies focused on the role of specific cytokines induced by radiation in the so-called “cytokine storm”. We will assess the time course changes of TNF-α, IL-1β, IL-6, CSF and TGF-β in blood as well as bone marrow and intestinal mucosa over 20 days following: UTS-1401 alone, 10 Gy irradiation, and the combination of UTS-1401 and radiation at a 24h interval. The results from these studies are expected to demonstrate an effective first-in-class compound, UTS-1401, which has a small molecular weight, is chemically stable, nontoxic, aqueous soluble and inexpensive with radiation mitigating properties which extend for a number of days following irradiation. The mechanism studies are expected to demonstrate UTS-1401 as a new class of agents for mitigating the cytokine storm consequent to the irradiation.", "keywords": [ "Animals", "Biologic Characteristic", "Biological", "Biological Assay", "Biological Availability", "Blood", "Bone Marrow", "Buffers", "Carboxylic Acids", "Cell Death", "Characteristics", "Chemicals", "Complex", "Data", "Development", "Dose", "Drug Delivery Systems", "Drug Kinetics", "Effectiveness", "Electrons", "Exposure to", "FDA approved", "Female", "Femur", "Formulation", "Gender", "Goals", "Hematopoietic", "Hematopoietic System", "Hematopoietic stem cells", "Hour", "Individual", "Inflammatory", "Interleukin-1 beta", "Interleukin-6", "Intestinal Mucosa", "Intestines", "Intravenous", "Ionizing radiation", "Isoxazoles", "Lethal Dose 50", "Measures", "Methods", "Molecular Weight", "Mus", "Nuclear", "Nuclear Accidents", "Nuclear Weapon", "Oral", "Pharmaceutical Preparations", "Plasma", "Property", "Radiation", "Radiation Accidents", "Radiation Dose Unit", "Radiation Injuries", "Radiation Protection", "Radiation Toxicity", "Radiation exposure", "Refrigeration", "Research", "Role", "Route", "Saline", "Sampling", "Series", "Solubility", "Spleen", "Swiss Mice", "Syndrome", "TNF gene", "Tartrates", "Technology", "Terrorism", "Testing", "Time", "Tissues", "Transforming Growth Factor beta", "United States National Institutes of Health", "War", "Weight", "Whole-Body Irradiation", "aqueous", "chemical stability", "cost effective", "cytokine", "cytokine release syndrome", "flexibility", "gastrointestinal", "gender difference", "intravenous administration", "irradiation", "male", "medical countermeasure", "mouse model", "novel", "radiation countermeasure", "radiation mitigation", "radiation mitigator", "radioprotected", "small molecule", "stem cells", "subcutaneous", "success" ], "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 } }, { "type": "Grant", "id": "15794", "attributes": { "award_id": "1R21EB037897-01", "title": "Programmable RNA-Based Sensors for In Situ Cell Type Detection and Response", "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": 32881, "first_name": "SHAWN PATRICK", "last_name": "MULVANEY", "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": 673600, "principal_investigator": { "id": 30867, "first_name": "Lei", "last_name": "Wang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2654, "ror": "", "name": "NORTHEASTERN UNIVERSITY", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "There is a technology gap in currently developed tools that simultaneously monitor, compute, and respond to both coding and non-coding RNA in real-time within living cells or patients. The continued existence of this gap represents an urgent unmet need because, until it is filled, the accuracy of RNA-based therapeutics remains limited in complex and evolving biological systems like differentiation or cancer. The long-term goal of this proposal is to develop safe, universal, and programmable synthetic biology tools that using both coding and non- coding RNAs as disease marker inputs and program outputs to trigger therapeutic responses in patients. The objective of this particular application is to develop an RNA-based sensor (using mRNA as the delivery modality) that detects integrated changes in both mRNA and miRNA for in situ therapeutic responses within living cells and mouse models, given the crucial role of ncRNAs, especially microRNAs (miRNAs), as key regulators of post- transcriptional gene regulation, which allow only the correct set of genes to be active in each cell type. The central hypothesis is that an RNA-based sensor integrating both mRNA and miRNA inputs, using Boolean logic gate computation, can improve the specificity of cell type identification in complex biological systems. This proposed work builds on our and other’s recent works on sensing individual RNA species like mRNA in live cells. The rationale for the proposed research is that a deeper understanding of disease progression, derived from the vast RNA sequencing resources now available in user-friendly databases, creates a timely and unique opportunity for synthetic biologists to develop tools that can precisely identify diseased cells based on their RNA species and levels in living cells or even in patients. This allows for the development of treatments that specifically target diseased cells while minimizing off-target effects on healthy cells. Additionally, the success of COVID-19 mRNA vaccines using lipid nanoparticle delivery systems highlights the potential to translate RNA-based genetic circuits into practical medical applications. Given these advances, we plan to develop two independent and complementary aims for in situ cell state sensing using endogenous mRNA and miRNA as inputs: AND logic gates (requiring both inputs for an output) in Aim 1 and NOR logic gates (requiring neither input for an output) in Aim 2. This platform has broad biomedical potentials. As a proof of concept, we will demonstrate its ability to distinguish breast cancer cells from normal breast epithelial cells, evaluating its translational potential using a syngeneic mouse model of triple-negative breast cancer, which lacks key cell surface targets in current therapies. The proposed platform is innovative because it develops new platform by integration of existing miRNA sensing and RNA detecting approaches in a previously unproven combinatorial logic computation format to address a significant unmet need for accurate cell type identification for basic and translational applications. The proposed research is significant, because in situ monitoring and intervening based on endogenous RNAs will be key to addressing this unmet need, transforming disease detection and treatment.", "keywords": [ "4T1", "Address", "Animal Model", "Award", "Biological", "Biomedical Engineering", "Breast Cancer Cell", "Breast Cancer therapy", "Breast Epithelial Cells", "COVID-19", "Cell Line", "Cell Physiology", "Cell model", "Cell surface", "Cells", "Clinical", "Code", "Complex", "Data", "Databases", "Detection", "Disease", "Disease Marker", "Disease Progression", "Double-Stranded RNA", "Elements", "Engineering", "Ensure", "Gene Expression", "Genes", "Genetic", "Goals", "Human", "Immune System Diseases", "In Situ", "Individual", "Logic", "MCF10A cells", "MDA MB 231", "Malignant Neoplasms", "Medical", "Messenger RNA", "MicroRNAs", "Mission", "Modality", "Modeling", "Monitor", "National Institute of Biomedical Imaging and Bioengineering", "Nature", "Nerve Degeneration", "Output", "Patients", "Performance", "Play", "Post-Transcriptional Regulation", "Proteins", "Publishing", "RNA", "RNA vaccine", "Regulation", "Regulator Genes", "Repression", "Research", "Resources", "Role", "Sampling", "Specificity", "Survival Rate", "System", "Technology", "Testing", "Time", "Tissues", "Translating", "United States National Institutes of Health", "Untranslated RNA", "Work", "biological systems", "cell type", "combinatorial", "complex biological systems", "design", "design and construction", "differential expression", "improved", "in vitro Model", "innovation", "lipid nanoparticle", "mRNA delivery", "mammary", "model design", "model organism", "molecular sequence database", "mouse model", "nanoparticle delivery", "novel", "novel strategies", "programs", "prototype", "response", "risk mitigation", "scaffold", "sensor", "single-cell RNA sequencing", "success", "synthetic biology", "targeted treatment", "therapeutic RNA", "therapy development", "tool", "transcriptome sequencing", "transcriptomics", "translational applications", "translational potential", "treatment response", "triple-negative invasive breast carcinoma", "user-friendly" ], "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": "15895", "attributes": { "award_id": "3R01AI170564-04S1", "title": "Single arm trial of menstrual cups among economically vulnerable women to reduce Bacterial vaginosis and STIs through reduced harmful sexual and menstrual practices", "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": 44333, "first_name": "ELEANORE JENNIFER", "last_name": "CHUANG", "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": 139891, "principal_investigator": { "id": 24638, "first_name": "Supriya Dinesh", "last_name": "Mehta", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 163, "ror": "https://ror.org/02mpq6x41", "name": "University of Illinois at Chicago", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 3396, "ror": "", "name": "RUSH UNIVERSITY MEDICAL CENTER", "address": "", "city": "", "state": "IL", "zip": "", "country": "United States", "approved": true }, "abstract": "In western Kenya, HIV prevalence is 16% among women in the general population, and 29% among the most economically constrained women. The HIV/STI epidemic overlaps with broader reproductive health concerns. Menstrual hygiene management (MHM) is a pervasive problem across low- and middle-income countries. In Phillips-Howards’ survey of over 3,400 women in rural Kenya, two-thirds of women in impoverished settings state they depend on their sexual partners to provide branded products. Economically vulnerable women at high risk for HIV and STI are uniquely challenged because many continue to have sex during menses, and engage in harmful MHM practices, such as vaginal insertion of sponges and cotton to maintain dryness. Led by co-investigator Phillips-Howard, a cluster-randomized study of 644 girls aged 14-16 years old in western Kenya compared reusable menstrual cups to usual menstrual practice and counseling; after 9 months, menstrual cup use resulted in 35% reduction (p=0.034) in Bacterial vaginosis (BV) prevalence and 56% reduction (p=0.001) in STI prevalence compared to other materials. Among 431 Kenyan secondary schoolgirls aged 14-21, we observed cloth use for menses was associated with a 1.72-fold increased odds of non-optimal vaginal microbiome (CST-IV vs. CST-I: aOR=1.90; 95% CI: 1.03–2.86). Over 18 months of observation prior to COVID-19, girls using menstrual cups to manage menses had 20% higher occurrence of Lactobacillus crispatus dominated CST-I (aRR=1.29; 95% CI: 1.08–1.53, controlling for age, and baseline STI and sexual activity). Menstrual cups designed for use during intercourse may help women prevent BV and STIs through hygienic menstrual practices and avoidance of harmful practices to maintain vaginal dryness during menses. Objective: This single-arm interventional trial seeks to evaluate the preliminary efficacy of menstrual cups on non-optimal vaginal microbiome (VMB), BV, and STIs of economically vulnerable women at high risk for STIs and HIV, assess safety profile, and understand implementation needs. In Aim 1, we will evaluate the impact of menstrual cups on VMB, BV, and STIs among 402 economically vulnerable women in semi-urban Kenya. In Aim 2, we will conduct integrated surveillance for enhanced detection of safety endpoints, risk of cup contamination, and mitigating or facilitating water, sanitation, hygiene (WASH) factors. In Aim 3, we will identify constructs for successful MHM program implementation using an implementation science framework. Future Directions: The biological protection suggested in a randomized setting, and our findings that unhygienic cloth use is associated with non-optimal VMB, while menstrual cup use increases optimal VMB composition, together provide rational justification for this trial, of relevance to economically challenged women globally. Assessing preliminary efficacy signal in conjunction with implementation characteristics and adverse events, will generate a comprehensive and necessary foundation for definitive assessment of effectiveness of menstrual cups as a multipurpose intervention for MHM, and to reduce BV and STIs.", "keywords": [ "16 year old", "Acceleration", "Address", "Adverse event", "Age", "Bacterial Vaginosis", "Behavioral", "Biological", "COVID-19", "Characteristics", "Chlamydia", "Counseling", "Data", "Decision Making", "Detection", "Discrimination", "Dryness", "Education", "Eligibility Determination", "Epidemic", "Extravasation", "Financial Support", "Focus Groups", "Foundations", "Future", "General Population", "Gonorrhea", "Gossypium", "Guidelines", "HIV", "HIV/STD", "Health Care", "High Risk Woman", "Hygiene", "Individual", "Intervention", "Intervention Trial", "Interview", "Investigation", "Kenya", "Knowledge", "Lactobacillus", "Life", "Location", "Medical", "Menstruation", "Odors", "Participant", "Phase", "Policies", "Porifera", "Poverty", "Practice Management", "Prevalence", "Privacy", "Randomized", "Reporting", "Reproductive Health", "Research Personnel", "Risk", "Rural", "Safety", "Sanitation", "Secondary Schools", "Secrecy", "Sex Behavior", "Sexual Partners", "Signal Transduction", "Soaps", "Surveys", "Taboo", "Technology", "Time", "Training", "Trichomonas Infections", "UNESCO", "Vagina", "Water", "Woman", "Wool", "Work", "aged", "arm", "biobehavior", "contextual factors", "cost", "cost effective", "cost effective intervention", "design", "diverse data", "effectiveness evaluation", "girls", "global health", "implementation context", "implementation determinants", "implementation evaluation", "implementation framework", "improved", "low and middle-income countries", "microbiome composition", "pandemic disease", "pharmacovigilance", "prevent", "primary outcome", "programs", "safety assessment", "scale up", "sex", "sexual and reproductive health", "social", "social stigma", "stem", "treatment arm", "trial design", "vaginal dryness", "vaginal microbiome", "women's reproductive health" ], "approved": true } }, { "type": "Grant", "id": "15898", "attributes": { "award_id": "1F31AI191665-01", "title": "Mechanisms of Pathogenesis in Staphylococcal Enterotoxin B-Induced Acute Respiratory Distress Syndrome", "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": 32556, "first_name": "TIMOTHY A", "last_name": "GONDRE-LEWIS", "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": 45662, "principal_investigator": { "id": 44336, "first_name": "Chloe", "last_name": "Weyer-Nichols", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 930, "ror": "", "name": "UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA", "address": "", "city": "", "state": "SC", "zip": "", "country": "United States", "approved": true }, "abstract": "Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by non-compliant lung, hypoxemia, protein-rich pulmonary edema, and cytokine storm. The COVID-19 pandemic highlighted ARDS as a significant public health burden that annually affects approximately 200,000 patients in the US with a 35-45% mortality rate. ARDS develops via a myriad of etiologies, though the most common underlying conditions in the US include pneumonia (44.9% of all cases) and nonpulmonary sepsis (46.8% of all cases). The gram-positive bacterial pathogen Staphylococcus aureus is one of the most commonly isolated pathogens in sepsis patients. S. aureus produces superantigens (SAgs), including Staphylococcal Enterotoxin B (SEB). SEB exposure can induce ARDS by activating up to 30% of the naïve T cell pool through the formation of non-specific cross-linkages between antigen-presenting cells (APCs) and T cells. The receptors involved in this interaction are classically believed to include Vβ TCRs, CD28, CD80/CD86, and MHC class II, though some studies suggest that MHC class II may be dispensable for inflammatory response. Interestingly, recent studies have demonstrated that the SARS-CoV-2 Spike protein contains a superantigen-like motif similar to SEB; additionally, the CDC has classified SEB as a Category B Biological Agent due to its ease of dissemination and inhalation toxicity. Therefore, murine models of SEB-induced ARDS can provide valuable insights into S. aureus and SARS-CoV-2 infection treatment, ARDS pathogenesis and prevention, and biological weapon response. My preliminary data demonstrates that the H2k C3H/HeJ mouse strain, but not the H2b C57BL/6J strain, are susceptible to SEB-induced ARDS, which suggests that H2 haplotype may play a role in superantigen response. Therefore, the central hypothesis of the proposed project is that C3H/HeJ mice are susceptible to SEB-induced ARDS due to alterations in MHC Class II, Vβ TCRs, CD28, or CD80/CD86, which allow SEB to more effectively form cross-linkages between APCs and T cells, thereby increasing SAg-mediated T cell activation and subsequent myeloid infiltration to the alveoli. To test this hypothesis, I propose the following specific aims: 1) Establish the cellular and molecular mechanisms of SEB-induced ARDS pathogenesis in C3H/HeJ and C57BL/6J mouse strains; 2) Determine whether strain-specific differences in MHC Class II, Vβ TCRs, CD28, or CD80/CD86 drives differential response to SEB in C3H/HeJ and C57BL/6J strains. The proposed experiments align with my goals for fellowship training and will allow me the opportunity to gain expertise in high-throughput immune cell profiling, transcriptome analysis, and in vivo approaches to elucidate immune response at the respiratory site. Furthermore, the proposed professional development plan will propel my career goals by enhancing my research independence.", "keywords": [ "Acute Respiratory Distress Syndrome", "Address", "Affect", "Alveolar", "Alveolus", "Antigen-Presenting Cells", "B-Lymphocytes", "Bacterial Infections", "Binding", "Biological Assay", "Biological Products", "Bronchoalveolar Lavage Fluid", "C3H/HeJ Mouse", "CD28 gene", "CD80 gene", "CD86 gene", "COVID-19 pandemic", "COVID-19 patient", "COVID-19/ARDS", "Categories", "Cells", "Characteristics", "Classification", "Congenic Mice", "Data", "Death Rate", "Development", "Development Plans", "Endothelium", "Epithelium", "Epitopes", "Etiology", "Excretory function", "Exhibits", "FDA approved", "Fellowship", "Flow Cytometry", "Genes", "Genetic", "Goals", "H2 gene", "Haplotypes", "Histocompatibility Antigens Class II", "Histopathology", "Hospitalization", "Hospitals", "Hypoxemia", "Immune", "Immune response", "Immunoassay", "Immunologics", "Infiltration", "Inflammatory Response", "Inhalation", "Lung", "MHC Class II Genes", "Major Histocompatibility Complex", "Mediating", "Molecular", "Molecular Target", "Monoclonal Antibodies", "Mouse Strains", "Mus", "Mycoses", "Myelogenous", "Pathogenesis", "Pathogenicity", "Patient Admission", "Patients", "Pharmacologic Substance", "Pneumonia", "Predisposition", "Prevention", "Proteins", "Public Health", "Pulmonary Edema", "Research", "Resistance", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "Sepsis", "Serum", "Site", "Spleen", "Staphylococcal Enterotoxin B", "Staphylococcus aureus", "Structure", "Superantigens", "T cell receptor repertoire sequencing", "T cell therapy", "T-Cell Activation", "T-Cell Receptor", "T-Lymphocyte", "Testing", "Toxic effect", "Training", "Virus Diseases", "bioweapon", "career", "cell type", "cellular targeting", "chemokine", "cytokine", "cytokine release syndrome", "experience", "experimental study", "in vivo", "insight", "interest", "lung injury", "mortality", "mouse model", "non-compliance", "pathogen", "pathogenic bacteria", "pharmacologic", "prevent", "receptor", "respiratory", "response", "septic patients", "single-cell RNA sequencing", "synthetic polymer Bioplex", "transcriptome", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "15742", "attributes": { "award_id": "1R21AI188400-01A1", "title": "Uncovering mechanisms that underpin bat virus virulence", "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": 32795, "first_name": "EUN-CHUNG", "last_name": "PARK", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-04", "end_date": "2027-07-31", "award_amount": 455692, "principal_investigator": { "id": 26531, "first_name": "Cara", "last_name": "Brook", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2613, "ror": "", "name": "UNIVERSITY OF CALIFORNIA BERKELEY", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Bats are reservoir hosts for zoonoses that cause the highest case fatality rates documented in humans, including rabies and related lyssaviruses, Hendra and Nipah henipaviruses, Ebola and Marburg filoviruses, and SARS and MERS coronaviruses. Bats exhibit limited disease upon infection with these viruses that cause extreme pathology in other mammals, likely due to robust and rapid innate and cell-mediated immune defenses, coupled with hyper-efficient mechanisms of DNA damage repair and dampened inflammatory pathways. Recent theoretical work in our lab demonstrates how these unique features of bat immunology and physiology—chiefly, constitutive antiviral immunity and resilience to inflammation that confers tolerance to immunopathology—should select for the evolution of high virus growth rates that, while avirulent to bats, are likely to cause pathology following spillover to non-bat, including human, hosts. Here, we seek to explicitly test the predictions of our theoretical model by carrying out experimental evolution of vesicular stomatitis virus (VSV) in bat cell cultures that span a range of both (Aim 1) constitutive antiviral and (Aim 2) inflammation tolerant phenotypes. Under Aim 1, we examine variation in VSV growth rate evolution and the rate of molecular evolution following serial passage of virus across a suite of Pteropus alecto bat cell lines that exhibit both intact (wildtype) and deficient (CRISPR knock-outs) antiviral immune functions. Under Aim 2, we leverage our lab’s unique system of primary bat fibroblast cell lines derived from related species spanning a range of longevities to evaluate whether cells derived from longer-lived species that demonstrate resilience to aging-related stressors also exhibit heightened tolerance of virus infection. We then compare VSV evolution following serial passage across cell lines that demonstrate variable resilience to aging-related stressors in vitro. We hypothesize that antiinflammatory properties in bat cells which confer resilience to aging stressors may also facilitate virus tolerance by limiting immunopathology and—by extension—drive the evolution of high growth rate viruses likely to generate pathology in non-bat hosts. Ultimately, we offer an explicit empirical test of the hypothesized mechanisms underpinning the extreme virulence of bat virus zoonoses.", "keywords": [ "Acceleration", "Aging", "Anti-Inflammatory Agents", "Anti-viral Response", "Automobile Driving", "Birds", "Body Size", "Case Fatality Rates", "Cell Culture Techniques", "Cell Line", "Cells", "Chiroptera", "Clustered Regularly Interspaced Short Palindromic Repeats", "Coupled", "DNA Repair", "Data", "Disease", "Ebola", "Evolution", "Exhibits", "Fibroblasts", "Filovirus", "Genes", "Genome", "Genus Pteropus", "Growth", "Harvest", "Hendra Virus", "Human", "IFNAR2 gene", "IRF1 gene", "IRF3 gene", "Immune", "Immune response", "Immunity", "Immunologics", "Immunology", "In Vitro", "Indiana", "Infection", "Inflammation", "Inflammatory", "Interferons", "Knock-out", "Link", "Literature", "Locomotion", "Longevity", "Lyssavirus", "Mammals", "Marburgvirus", "Mediating", "Metabolic", "Metabolic stress", "Middle East Respiratory Syndrome Coronavirus", "Molecular", "Molecular Evolution", "Nipah Virus", "Paper", "Pathology", "Pathway interactions", "Phenotype", "Physiological", "Physiology", "Plaque Assay", "Process", "Property", "Public Health", "RNA", "Rabies", "Regulator Genes", "Research", "Residual state", "Resistance", "SARS coronavirus", "Secondary to", "Serial Passage", "Serotyping", "Signal Transduction", "System", "Testing", "Theoretical model", "Variant", "Vesicular stomatitis Indiana virus", "Viral", "Viral Load result", "Virulence", "Virulent", "Virus", "Virus Diseases", "Work", "Zoonoses", "aging related", "anti aging", "antiviral immunity", "burden of illness", "cellular resilience", "comparative", "cost", "experience", "experimental study", "extend lifespan", "immune function", "immunopathology", "life span", "oxidative damage", "predictive modeling", "rapid growth", "resilience", "resilience in aging", "response", "stressor", "theories", "trait", "transcriptome sequencing", "transcriptomics", "transmission process", "viral resistance" ], "approved": true } }, { "type": "Grant", "id": "15755", "attributes": { "award_id": "4R00HL173656-03", "title": "Mesenchymal cell plasticity and signaling in lung regeneration", "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": 32818, "first_name": "MARISOL", "last_name": "ESPINOZA-PINTUCCI", "orcid": "", "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2025-08-04", "end_date": "2028-07-31", "award_amount": 248999, "principal_investigator": { "id": 31843, "first_name": "Dakota L", "last_name": "Jones", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2625, "ror": "", "name": "UNIVERSITY OF IOWA", "address": "", "city": "", "state": "IA", "zip": "", "country": "United States", "approved": true }, "abstract": "Regeneration of the lung following severe injury is an imperfect process and frequently leads to permanently altered lung structure and dysplastic cell types. After severe injury, such as influenza or COVID-19, the alveolus can either regenerate in form and function (adaptive regeneration) or be replaced by airway-derived dysplastic epithelium (maladaptive repair). These maladaptive cells and structures do not participate in gas exchange and likely contribute to the long-term reduction in pulmonary function seen in some patients from severe lung injury, highlighting the need for the development of new therapeutics with which to promote functional adaptive alveolar regeneration. Developing these new therapies will require a comprehensive understanding of not only the progenitor cells and their functions after injury, but also how they signal and interact with other cells within the injured alveolar niche. The alveolus is composed of a fragile layer of epithelium surrounded by a dense network of mesenchymal cells which serve important roles in paracrine signaling within the alveolar niche. Recent work from our lab and others has demonstrated the heterogeneity of these cells, identifying two key populations of alveolar mesenchyme, those that express Pdgfra (alpha+) and those that express Pdgfrb (beta+). Based on my extensive preliminary data demonstrating a key role of alpha+ cell proliferation, plasticity, and Notch signaling in alveolar regeneration after viral injury in both mouse and human lungs, I will test the hypothesize that specific mesenchymal cell lineages that arise from injury-induced plasticity establish and maintain the maladaptive epithelial regenerative response, in part through Notch mesenchymal-epithelial signaling. In Aim 1 of this proposal, I will examine how alpha+ cell proliferation and plasticity are defined and maintained after viral injury. The proposed research in Aim 1 will further develop my skills in transcriptomic and epigenomic analyses and physiological impacts of injury on lung function. In the independent phase outlined in Aim 2, I will define the importance of Notch mediated mesenchymal paracrine signaling within the alveolar niche during adaptive vs maladaptive regeneration. My primary mentor, Dr. Edward Morrisey is an internationally renowned lung biologist who has identified many key cell types and pathways which drive regeneration of the injured lung. I have also assembled a diverse advisory committee of experts in bioinformatics, epigenetics, physiologic readouts of recovery of lung function after injury, and Notch signaling who will assist me in training of these areas. The proposed work will be conducted at the University of Pennsylvania, where I will benefit from the rich intellectual environment, wide-ranging resources, collaborative scientific community in pulmonary and mesenchymal biology, and the full support of the institution. Together, this proposal outlines a rigorous research and training plan that will establish the foundation to advance my career in lung and mesenchymal cell biology.", "keywords": [ "Advisory Committees", "Alpha Cell", "Alveolar", "Alveolus", "Area", "Beta Cell", "Bioinformatics", "Biological Assay", "Biology", "COVID-19", "COVID-19 patient", "Cell Differentiation process", "Cell Lineage", "Cell Physiology", "Cell Proliferation", "Cell division", "Cells", "Cellular biology", "Chronic", "Chronic lung disease", "Coculture Techniques", "Communities", "Confocal Microscopy", "Data", "Development", "Distal", "Environment", "Epigenetic Process", "Epithelial Cells", "Epithelium", "Equilibrium", "Exhibits", "Foundations", "Future", "Gases", "Genetic Transcription", "Genomics", "Heterogeneity", "Human", "Influenza", "Injury", "Institution", "International", "Intervention", "Label", "Lead", "Lentivirus", "Lineage Tracing", "Lung", "Lung infections", "Maintenance", "Mediating", "Mentors", "Mesenchymal", "Mesenchyme", "Modeling", "Mus", "NOTCH3 gene", "Natural regeneration", "Organoids", "Paracrine Communication", "Pathologic", "Pathology", "Pathway interactions", "Patients", "Pennsylvania", "Phase", "Physiological", "Population", "Positioning Attribute", "Process", "Proliferating", "Recovery", "Regenerative response", "Research", "Research Personnel", "Resources", "Role", "Signal Transduction", "Sorting", "Structure", "Testing", "Therapeutic", "Time", "Training", "Transgenic Mice", "Universities", "Viral", "Viral Respiratory Tract Infection", "Virus Diseases", "Work", "alveolar epithelium", "alveolar homeostasis", "career", "cell type", "epigenomics", "epithelium regeneration", "influenza infection", "injured", "insight", "keratinization", "lung injury", "lung regeneration", "multiple omics", "notch protein", "novel", "novel therapeutics", "post-doctoral training", "progenitor", "pulmonary", "pulmonary function", "receptor", "regeneration function", "regenerative", "repaired", "response", "severe injury", "single cell genomics", "single-cell RNA sequencing", "skills", "spatiotemporal", "stem cells", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "15790", "attributes": { "award_id": "1R21AI193738-01", "title": "Combined pathogen and host-based diagnostic to identify etiology of lower respiratory tract infection", "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": "2025-08-05", "end_date": "2027-07-31", "award_amount": 244044, "principal_investigator": { "id": 7629, "first_name": "GAYANI", "last_name": "TILLEKERATNE", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 246, "ror": "https://ror.org/00py81415", "name": "Duke University", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 2652, "ror": "", "name": "DUKE UNIVERSITY", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "Lower respiratory tract infection (LRTI) is the leading infectious cause of death globally. Despite its prevalence, the exact etiology of LRTI is unknown in the vast majority of cases. Even when identified, bacteria or viruses in nasopharyngeal (NP) or sputum samples may be colonizers in the upper tract rather than the cause of infection in the lower tract. Unclear LRTI etiology results in the overprescription of antibacterials, which in turn drives the global crisis in antibacterial resistance. Antibacterial overprescription and resistance are greater in low- or middle-income countries (LMICs), where basic diagnostic capacity is limited. Host-based diagnostics, which assess the host immune response to infection, have recently emerged as a complementary method to pathogen-based diagnostics for identifying the class of respiratory infection. Our team has developed host- based gene expression classifiers using peripheral blood samples to differentiate viral versus bacterial respiratory infection. The goal of the current application is to develop an integrated diagnostic that uses a single, non-invasive NP sample to detect both pathogen and host response to identify LRTI etiology. The following specific aims will be conducted at a collaborative research site in Sri Lanka: 1) Develop a novel NP- based gene expression classifier to identify viral versus non-viral LRTI, and 2) Design and validate an integrated pathogen and host gene expression test to identify viral versus non-viral LRTI using a quantitative real-time polymerase chain reaction (qRT-PCR) assay. For aim 1, we will use previously collected NP samples from clinically adjudicated viral and non-viral LRTI patients in Sri Lanka and conduct low-input RNA sequencing. Machine-learning approaches will identify host gene expression classifiers that discriminate viral versus non-viral LRTI. For aim 2, the genes identified in the NP-based classifier, as well as nucleic acid targets for two respiratory viruses that are frequently implicated in true infection as well as asymptomatic colonization (SARS-COV-2 and human rhinovirus [HRV]), will be migrated onto TaqMan Low-Density Array (TLDA) cards. A prospective cohort of patients will be enrolled in Sri Lanka, and etiological testing and clinical adjudications will be performed as the reference standard to identify viral (including SARS-CoV-2 and HRV) and non-viral LRTI. Using an optimally retrained and parsimonious viral versus non-viral classifier, we will perform a feasibility analysis of incorporating pathogen detection and host-response classifier. Among samples with TLDA-based pathogen detection for SARS-CoV-2 or HRV, performance of the host- response classifier to distinguish viral versus non-viral LRTI will be assessed. Successful completion of these aims will result in the development of a novel diagnostic that integrates host and pathogen detection using a single, non-invasive NP sample to identify the etiology of LRTI. Translation of this assay to a rapid platform will help shift the current diagnostic paradigm for LRTI.", "keywords": [ "2019-nCoV", "Anti-Bacterial Agents", "Bacteria", "Bacterial Drug Resistance", "Bacterial Infections", "Biological", "Biological Assay", "Blood Tests", "Blood specimen", "Bronchoscopy", "COVID-19 detection", "Cause of Death", "Clinical", "Country", "Data", "Development", "Diagnostic", "Diagnostic Procedure", "Enrollment", "Etiology", "Fever", "Future", "Gene Expression", "Gene Targeting", "Genes", "Goals", "Hour", "Human", "Immune response", "Income", "Infection", "Influenza", "Lower Respiratory Tract Infection", "Machine Learning", "Manuscripts", "Methods", "Nasopharynx", "Nucleic Acids", "Pathogen detection", "Patients", "Performance", "Pilot Projects", "Polymerase Chain Reaction", "Prevalence", "Procedures", "Prospective cohort", "Reference Standards", "Research", "Resistance", "Respiratory Signs and Symptoms", "Respiratory Tract Infections", "Respiratory syncytial virus", "Rhinovirus", "Sampling", "Site", "Sputum", "Sri Lanka", "Testing", "Time", "Training", "Translating", "Upper respiratory tract", "Viral", "Virus", "Work", "adjudication", "biobank", "density", "design", "differential expression", "experience", "migration", "novel", "novel diagnostics", "pathogen", "peripheral blood", "prospective", "respiratory virus", "transcriptome sequencing", "translation assay" ], "approved": true } } ], "meta": { "pagination": { "page": 1405, "pages": 1419, "count": 14184 } } }