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141,003 grants matching “cytokine”
Tracking SARS-CoV-2 one molecule at a time: Spatiotemporal investigation of coronavirus replication dynamics and host response in single cells in vitro and in vivo
$650,415Charles M. Rice · Rockefeller University · R01 · FY2024 · AI
Using a Randomized Prevention Trial to Understand the Health Benefits of Supportive Couple Relationships among Rural African American Adults
$650,396Steven R Beach · University Of Georgia · R01 · FY2020 · AG
Contribution of maternal immune activation, viral infection and epigenetics to autism--a community-based case control study
$650,386Carolyn M Salafia · Institute For Basic Res In Dev Disabil · R01 · FY2025 · HD
Cpdm: Cloning a Gene that Regulates Eosinophil Function
$650,364John Paul Sundberg · Jackson Laboratory · R01 · FY2014 · AR
Naturally Acquired Immunity to Malaria during the Epidemiologic Transition in Ken
$650,352James Walter Kazura · Case Western Reserve University · R01 · FY2012 · AI
Inflammation and Therapy for Respiratory Virus Infection
$650,338Helene Rosenberg · National Institute Of Allergy And Infectious Diseases · ZIA · FY2019 · AI
Eosinophils, Inflammation and Immunity
$650,338Helene Rosenberg · National Institute Of Allergy And Infectious Diseases · ZIA · FY2019 · AI
Epidemiology of Diabetes Complications (EDC) Phase II: renewal
$650,335Trevor J. Orchard · University Of Pittsburgh At Pittsburgh · R37 · FY2011 · DK
Development of first-in-class ST2 inhibitors for treating graft-versus-host disease
$650,311Chao-Yie Yang · University Of Tennessee Health Sci Ctr · R01 · FY2020 · HL
Metabolic regulation of human DNA methylation clocks
$650,280Martin Picard · New York State Psychiatric Institute Dba Research Foundation For Mental Hygiene, Inc · R01 · FY2022 · AG
Immune correlates of LTBI in HIV-exposed infants
$650,269Savita Pahwa · University Of Miami School Of Medicine · R01 · FY2019 · AI
COVID-19 vaccine development research
$650,195Barbara Felber · Division Of Basic Sciences - Nci · ZIA · FY2021 · CA
Epidemiology of Diabetes Complications (EDC) Phase II: renewal
$650,190Trevor J. Orchard · University Of Pittsburgh At Pittsburgh · R37 · FY2016 · DK
The role of biobehavioral factors and anti-inflammatory medications on the ovarian tumor immune response
$650,127Shelley S Tworoger · Oregon Health & Science University · R01 · FY2025 · CA
Uncoupling obesity from breast cancer in African American women
$650,118Gerald V Denis · Boston University Medical Campus · U01 · FY2017 · CA
Multi-level predictors of structural racism and discrimination and associations with health and well-being across the life course in diverse families
$650,101Jerica M Berge · University Of Minnesota · R01 · FY2023 · AT
Evaluating the protective effect of a tissue selective estrogen complex (TSEC) in women with newly diagnosed ductal carcinoma in situ
$650,068Swati Kulkarni · Northwestern University At Chicago · R01 · FY2019 · CA
(PQ3) Cellular and Molecular Mechanisms Driving Myeloid Compartment Variation in Human Triple Negative Breast Cancer
$650,064Anna Karolina Palucka · Jackson Laboratory · R01 · FY2019 · CA
CIS-REGULATORY CIRCUITS FOR ILC FUNCTION AND PLASTICITY
$650,048Marco Colonna · Washington University · R01 · FY2021 · AI
CIS-REGULATORY CIRCUITS FOR ILC FUNCTION AND PLASTICITY
$650,048Marco Colonna · Washington University · R01 · FY2020 · AI
Therapeutic enzyme depletion of L-serine for cancer treatment
$650,029Everett Stone · University Of Texas At Austin · R01 · FY2023 · CA
A Multipronged Interrogation of Large-Scale Omics Data to Reveal COVID-19 Pathways
$650,002Carlos Cruchaga · Washington University · RF1 · FY2020 · AG
** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** MAREK'S DISEASE (MD) IS A CANCER OF CHICKENS FOR WHICH A VACCINE INJECTED INTO THE EGGS OF CHICKENS PRIOR TO HATCH PROVIDES LIFELONG PREVENTION OF THIS CANCER. MD IS CAUSED BY A VIRUS (MAREK'S DISEASE VIRUS, MDV) AND THE VACCINES THAT PREVENT MD ARE COMPOSED OF RELATED VIRUSES THAT DO NOT CAUSE DISEASE. HOW THESE RELATED VIRUSES TRAIN THE IMMUNE SYSTEM TO PROVIDE SUCH A LONGLASTING ANTI-VIRAL/ANTI-CANCER RESPONSE IS CURRENTLY UNKNOWN, AS THE VACCINE VIRUSES HAVE VERY LIMITED REPLICATION IN COMMERCIAL CHICKENS DUE TO MATERNAL ANTIBODIES AND THEIR HAVING BEEN BRED FOR RESISTANCE TO MD. IT IS OUR HYPOTHESIS THAT SMALL VESICLES (THE SIZE OF VIRUSES) PRODUCED BY SOME INFECTED CELLS IN THE BODY OF THE CHICKENS PROVIDE THIS LIFELONG PROTECTION FROM MD. THESE SMALL VESICLES, TERMED EXOSOMES, CONTAIN PROTEINS, LIPIDS, DNAS AND RNAS THAT WE BELIEVE CARRY BITS OF THE VIRUS WHICH THEN PROVIDE THESE TO SPECIALIZED CELLS OF THE IMMUNE SYSTEM THAT PATTERN THE WAY THE BODY RESPONDS TO CHALLENGE IN THE FIELD.AS DISEASE-CAUSING MDVS CAN BE FOUND IN MOST, IF NOT ALL CHICKEN HOUSES IN THE US, IN THE FORM OF INFECTIOUS DANDER (DEAD SKIN CELLS), CHALLENGE WITH MDV IS CONSIDERED TO BE HIGHLY LIKELY DURING THE LIFE OF THE CHICKEN.EXOSOMES ARE INCREDIBLY PREVALENT (~TEN BILLION PER ML OF SERUM) IN ALL BIOLOGICAL FLUIDS (SERUM, TEARS, URINE, SEMEN, LYMPH, ETC.). TO UNDERSTAND HOW EXOSOMES CONFER IMMUNE PROTECTION, WE HAVE BEEN EXAMINING THEIR UPTAKE BY A PHAGOCYTIC CELL LINE THAT HAS BEEN TREATED WITH CHEMICALS AND PROTEINS TO BECOME DENDRITIC CELLS (DCS), A POPULATION ESSENTIAL FOR THE PROPER PATTERNING OF IMMUNTY. IN THE PROPOSED WORK, WE TRY TO IDENTIFY WHETHER THESE CELLS, ONCE TREATED WITH EXOSOMES FROM THE SERUM OF BIRDS WHICH HAVE BEEN VACCINATED AND HAVE SURVIVED CHALLENGE WITH HIGHLY-VIRULENT MDVS, WILL STIMULATE IMMUNE CELLS TO BECOME ACTIVATED. WE ALSO PLAN TO DETERMINE IF THESE EXOSOMES CAN WORK TOGETHER WITH VACCINES OR CAN BE USED AS VACCINES THEMSELVES TO AUGMENT OR PREVENT DISEASE IN CHICKENS THAT WILL THEN BE CHALLENGED WITH A HIGHLY-VIRULENT MDV.IN ADDITION, SINCE CANCER CELLS PRODUCE EXOSOMES THAT HAVE BEEN ASSOCIATED WITH PROGRESSION AND DISSEMINATION (METASTASIS), WE PLAN TO USE EXOSOMES ISOLATED FROM THE SERUM OF TUMOR-BEARING CHICKENS TO DETERMINE IF THESE ALTER OR PREVENT APPROPRIATE PATTERNING OF THE IMMUNE RESPONSE. TO DO THIS, WE WILL BE TREATING THE PHAGOCYTIC CELL LINE (IN THE VARIOUS FORMS PATTERNED BY CYTOKINES) WITH KNOWN AGONISTS (SPECIFIC INDUCERS) OF DIFFERENT TYPES OF INNATE IMMUNE RESPONSES (INFLAMMATION, INTERFERON RESPONSES, ETC.) AND THEN MEASURE THEIR EFFECTS COMPARED TO NON-TREATED CONTROLS (FOR WHICH WE HAVE SIGNIFICANT DATA SHOWING WHAT A NORMAL RESPONSE WOULD BE). IN ADDITION, WE PLAN TO DETERMINE IF ADMINISTRATION OF THESE EXOSOMES FROM TUMOR-BEARING BIRDS AFFECTS MD VACCINES AND PREVENTS THEM FROM PROVIDING PROTECTION FROM CHALLENGE.FINALLY, WE WANT TO TRY AND UNDERSTAND WHAT CELLS IN THE BODY ARE INFECTED BY MDV BUT,THEN PRODUCE THE EXOSOMES WHICH HELP TO PROVIDE PROTECTION. PRELIMINARY STUDIES SUGGEST THAT PHAGOCYTIC CELLS DO IN FACT BECOME INFECTED, BUT THAT THEY DO NOT BECOME INFECTIOUS (ABLE TO TRANSMIT INFECTION). WE PLAN TO STUDY THIS VIRUS-HOST CELL INTERACTION IN ORDER TO BETTER UNDERSTAND HOW MD VACCINES PRODUCE EXOSOMES THAT GIVE RISE TO SYSTEMIC PROTECTION. THIS WORK IS FUNDAMENTAL TO OUR UNDERSTANDING OF HOW MD VACCINES WORK AND MY YIELD INSIGHT INTO THE DEVELOPMENT OF VACCINES FOR HUMAN VIRUS-INDUCED MALIGNANCIES.
$650,000University Of Delaware · · FY2023 · National Institute of Food and Agriculture
TUMOR IMMUNOTHERAPY WITH BIODEGRADABLE MICROSPHERES
$650,000Therapyx, Inc. · R44 · FY2003 · CA
** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** PARTURITION IS A RISKY PERIOD WHEN THE INCIDENCE OF DISEASE IS HIGH IN DAIRY COWS. THESE DISEASES INCLUDE BOTH METABOLIC (KETOSIS, DISPLACED ABOMASUM, HYPOCALCEMIA, AND RETAINED PLACENTA) AND INFECTIOUS DISEASES (MASTITIS AND METRITIS). ACCORDING TO THE USDA 2007 NAHMS REPORT, 37% OF COWS EXPERIENCE AT LEAST ONE DISORDER DURING THE POSTPARTUM PERIOD. THESE DISEASES ARE QUITE COSTLY. TO PROVIDE AN EXAMPLE OF THIS, THE COST OF CLINICAL MASTITIS DURING EARLY LACTATION IS ESTIMATED AT $444 PER CASE, AND THE ANNUAL COST OF MASTITIS FOR THE US DAIRY INDUSTRY IS ESTIMATED AT $2 BILLION. AS SUCH, INNOVATIVE ANIMAL HEALTH SOLUTIONS WILL BE REQUIRED TO SOLVE COMPLEX PROBLEMS IN AN ECONOMICALLY STRAINED DAIRY INDUSTRY. IN THIS RESEARCH PROPOSAL, WE STRIVE TO IMPROVE OUR UNDERSTANDING OF THE NEXUS BETWEEN SYSTEMIC INFLAMMATION AND MAMMARY GLAND HEALTH IN PERIPARTURIENT DAIRY CATTLE.THE OBJECTIVE OF THIS PROPOSAL IS TO ELUCIDATE THE DIRECT EFFECTS OF CHRONIC LOW-GRADE SYSTEMIC INFLAMMATION ON MAMMARY GLAND HEALTH. ELEVATED CONCENTRATIONS OF INFLAMMATORY MARKERS DURING THE PERIPARTUM PERIOD HAVE BEEN ASSOCIATED WITH DISEASES INCLUDING MASTITIS DURING THE POSTPARTUM PERIOD IN DAIRY CATTLE. NEVERTHELESS, THESE ASSOCIATIONS DO NOT NECESSARILY DEMONSTRATE A CAUSAL RELATIONSHIP. WE HYPOTHESIZE THAT LOW-GRADE SYSTEMIC INFLAMMATION WILL IMPAIR MAMMARY GLAND IMMUNE RESPONSES AND INCREASE SEVERITY DURING AN INTRAMAMMARY CHALLENGE.THEREFORE, IN AIM 1, WE PROPOSE TO STUDY THE ROLE OF CHRONIC, LOW-GRADE SYSTEMIC INFLAMMATION IN POSTPARTUM DAIRY CATTLE ON MAMMARY GLAND IMMUNE RESPONSES DURING AN INTRAMAMMARY STREPTOCOCCUS UBERIS CHALLENGE. FOR THIS OBJECTIVE, WE WILL USE RECOMBINANT TUMOR NECROSIS FACTOR Α AS A MODEL PRO-INFLAMMATORY CYTOKINE TO INDUCE CHRONIC, LOW-GRADE INFLAMMATION. FOR AIM 2, WE PROPOSE TO ASSESS THE EFFECTS OF POSTPARTUM ADMINISTRATION OF MELOXICAM, A NON-STEROIDAL ANTI-INFLAMMATORY DRUG USED TO INHIBIT POSTPARTUM SYSTEMIC INFLAMMATION, ON MAMMARY GLAND IMMUNE RESPONSES DURING AN INTRAMAMMARY STREPTOCOCCUS UBERIS CHALLENGE. WE ANTICIPATE THAT SYSTEMIC INFLAMMATION WILL IMPAIR MAMMARY GLAND IMMUNE RESPONSES LEADING TO A MORE SEVERE INTRAMAMMARY INFECTION, WHEREAS POSTPARTUM MELOXICAM ADMINISTRATION WILL IMPROVE MAMMARY GLAND IMMUNE RESPONSES LEADING TO AN ENHANCED ABILITY TO CONTROL AND ELIMINATE THE STREPTOCOCCUS UBERIS.THE PROPOSED STUDY WILL DEFINE FOR THE FIRST TIME THE IMPACT OF SYSTEMIC INFLAMMATION ON MAMMARY GLAND IMMUNE RESPONSES. POSTPARTUM DAIRY CATTLE EXPERIENCE CHRONIC, LOW-GRADE SYSTEMIC INFLAMMATION, WHICH HAS BEEN ASSOCIATED WITH DISEASE INCIDENCE. NEVERTHELESS, IT IS UNCLEAR IF THIS SYSTEMIC INFLAMMATORY RESPONSE IS PROTECTIVE OR PATHOLOGICAL. AS SUCH, IT HAS BEEN INCREDIBLY CHALLENGING TO DEVELOP SOLUTIONS FOR POSTPARTUM DISORDERS BECAUSE WE DO NOT UNDERSTAND THE PATHOLOGY OF MANY OF THESE DISORDERS AND DISEASES. THEREFORE, IT COMES AS NO SURPRISE THAT THE INCIDENCE OF MANY CLINICAL DISEASES DURING THE POSTPARTUM PERIOD INCLUDING,CLINICAL MASTITIS HAVE STUBBORNLY REMAINED UNCHANGED OVER THE PAST FEW DECADES. FUTURE RESEARCH PROJECTS ARE NEEDED TO DEVELOP SOLUTIONS FOR POSTPARTUM HEALTH PROBLEMS; HOWEVER, THESE PROJECTS MUST BE INFORMED BY STUDIES EVALUATING THE CAUSES OF THESE DISORDERS TO IDENTIFY POTENTIALLY EFFECTIVE TREATMENT STRATEGIES. THE RESULTS FROM THESE STUDIES WILL BE USED TO INFORM FUTURE RESEARCH PROJECTS TO DEVELOP SOLUTIONS TO REDUCE THE INCIDENCE OF POSTPARTUM DISORDERS INCLUDING MASTITIS. THE LONG-TERM GOALS OF THESE PROJECTS ARE TO IMPROVE DAIRY CATTLE HEALTH AND REDUCE ANTIMICROBIAL USAGE.
$650,000South Dakota State University · · FY2024 · National Institute of Food and Agriculture