A5072436976- Malaria Research and Control
- Mosquito-borne diseases and control
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Genetic and phenotypic traits in livestock
- Genetic Mapping and Diversity in Plants and Animals
- Vector-borne infectious diseases
- Animal Genetics and Reproduction
- CRISPR and Genetic Engineering
- Genomics and Rare Diseases
- Hepatitis B Virus Studies
- CAR-T cell therapy research
- Complement system in diseases
- Invertebrate Immune Response Mechanisms
- Reproductive Biology and Fertility
- Molecular Biology Techniques and Applications
- Metallurgy and Material Science
- Milk Quality and Mastitis in Dairy Cows
- vaccines and immunoinformatics approaches
- Bone and Dental Protein Studies
- interferon and immune responses
- Immune Response and Inflammation
- Genetics and Neurodevelopmental Disorders
- dental development and anomalies
National Institutes of Health
2003-2024
National Center for Advancing Translational Sciences
2023-2024
Naval Medical Research Command
2008-2021
Henry M. Jackson Foundation
2015-2020
Jackson Foundation
2015-2020
Walter Reed Army Institute of Research
2010-2016
U.S. President's Malaria Initiative
2008
National Cancer Institute
2003-2007
National Cancer Institute
2003-2004
Malaghan Institute of Medical Research
2000-2003
The Booroola fecundity gene (FecB) increases ovulation rate and litter size in sheep is inherited as a single autosomal locus. effect of FecB additive for (increasing by about 1.6 corpora lutea per cycle each copy) has been mapped to chromosome 6q23–31, which syntenic human 4q21–25. Bone morphogenetic protein IB (BMP-IB) receptor (also known ALK-6), binds members the transforming growth factor-β (TGF-β) superfamily, located region containing have mutation (Q249R) highly conserved...
A medium-density linkage map of the ovine genome has been developed. Marker data for 550 new loci were generated and merged with previous sheep map. The comprises 1093 markers representing 1062 unique (941 anonymous loci, 121 genes) spans 3500 cM (sex-averaged) autosomes 132 (female) on X chromosome. There is an average spacing 3.4 between autosomal 8.3 highly polymorphic [polymorphic information content (PIC) ≥ 0.7] loci. largest gap 32.5 cM, number gaps >20 or regions where are missing...
Background A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both reduce the morbidity this parasite as a key component in efforts eradicate malaria worldwide. Vivax protein 1 (VMP001), novel chimeric that incorporates amino- carboxy- terminal regions of circumsporozoite (CSP) truncated repeat region contains sequences from VK210 (type 1) VK247 2) parasites, was developed candidate for global use. Methods We conducted first-in-human Phase dose escalation study...
Immunoglobulin class switch recombination (Ig CSR) involves DNA double strand breaks (DSBs) at recombining regions and repair of these by nonhomologous end-joining. Because the protein kinase ataxia telengiectasia (AT) mutated (ATM) plays a critical role in DSB AT patients show abnormalities Ig isotype expression, we assessed ATM CSR examining ATM-deficient mice. In response to T cell–dependent antigen (Ag), Atm−/− mice secreted substantially less Ag-specific IgA, IgG1, IgG2b, IgG3, total...
The c-Jun NH2-terminal kinase (JNK) signaling pathway is induced by cytokines and stress stimuli implicated in cell death differentiation, but the specific function of this depends on type. Here we examined role JNK1 JNK2 CD8+ T cells. Unlike CD4+ cells, absence causes increased interleukin (IL)-2 production proliferation In contrast, JNK1-deficient cells are unable to undergo antigen-stimulated expansion vitro, even presence exogenous IL-2. hypoproliferation these associated with impaired...
At present, radiation-attenuated plasmodia sporozoites (γ-spz) is the only vaccine that induces sterile and lasting protection in malaria-naive humans laboratory rodents. However, γ-spz are not without risks. For example, heterogeneity of could explain occasional breakthrough infections. To avoid this possibility, we constructed a double-knockout P. berghei parasite by removing 2 genes, UIS3 UIS4, up-regulated infective spz. We evaluated Pbuis3(-)/4(-) parasites for protective efficacy...
A phase 2a RTS,S/AS malaria vaccine trial, conducted previously at the Walter Reed Army Institute of Research, conferred sterile immunity against a primary challenge with infectious sporozoites in 40% 80 subjects enrolled study. The frequency Plasmodium falciparum circumsporozoite protein (CSP)-specific CD4+ T cells was significantly higher protected as compared to non-protected subjects. Intrigued by these unique vaccine-related correlates protection, present study we asked whether RTS,S...
Abstract The CD28 costimulatory pathway is critical to T cell activation. Blockade of the interaction with its ligands CD80 and CD86 using CTLA4-Ig has been proposed as a therapy for number immune-based disorders. We have used murine model influenza virus infection study role CD28-dependent costimulation in development antiviral immune responses. In vivo treatment block reduced virus-specific cytotoxicity IFN-γ production by bronchoalveolar lavage fluid CD8+ lymphocytes vitro. It also...
Background: The current road to developing treatments for rare diseases is often slow, expensive, and riddled with risk. Change needed improve the process, both in how we think about disease treatment development infrastructure build support ongoing science. National Institutes of Health (NIH)-supported Rare Diseases Clinical Research Network (RDCRN) was established advance diagnosis, management, promote highly collaborative, multi-site, patient-centric, translational, clinical research....
Invariant NKT (iNKT) cells are a population of TCRalphabeta-expressing that unique in several respects. In contrast to conventional T cells, iNKT selected the thymus for recognition CD1, rather than MHC class I or II, and by CD1-expressing double-positive thymocytes, thymic stromal responsible positive selection cells. We have probed further requirements cell development find these highly sensitive B7-CD28 costimulatory interactions, as evidenced substantially decreased numbers CD28 B7...
ABSTRACT Plasmodium vivax is the major cause of malaria outside sub-Saharan Africa and inflicts debilitating morbidity consequent economic impacts in developing countries. In order to produce a P. vaccine for global use, we have previously reported development novel chimeric recombinant protein, VMP001, based on circumsporozoite protein (CSP) . Very few adjuvant formulations are currently available human use. Our interest evaluate second-generation identify combinations adjuvants capable...
In this phase 1 clinical trial, healthy adult, malaria-naïve subjects were immunized with radiation-attenuated Plasmodium falciparum sporozoites (PfRAS) by mosquito bite and then underwent controlled human malaria infection (CHMI). The PfRAS model for immunization against had previously induced >90 % sterile protection homologous CHMI. This study was to further explore the safety, tolerability protective efficacy of provide biological specimens characterize immune responses identify antigens...
Abstract The Fus1 gene resides in the critical 3p21.3 human chromosomal region deleted lung and breast cancers. Recently, tumour suppressor properties of were confirmed experimentally by intra‐tumoural administration that suppressed experimental metastasis mice. We generated ‐deficient mice viable, fertile, demonstrated a complex immunological phenotype. Animals with disrupted developed signs autoimmune disease, such as vasculitis, glomerulonephritis, anaemia, circulating autoantibodies,...
Background Immunization with radiation-attenuated sporozoites (RAS) by mosquito bite provides >90% sterile protection against Plasmodium falciparum (Pf) malaria in humans. RAS invade hepatocytes but do not replicate. CD8+ T cells recognizing parasite-derived peptides on the surface of infected are likely primary protective mechanism. We conducted a randomized clinical trial immunization to assess safety, achieve 50% vaccine efficacy (VE) controlled human infection (CHMI), and generate...
Abstract The CD80/86-CD28 and CD40-CD40 ligand costimulatory pathways are essential for Th cell-dependent B cell responses that generate high-affinity, class-switched Ab in vivo. Disruption of either pathway results defective vivo humoral immune responses, but it remains unclear to what extent this is due deficient activation cells and/or cells. To address issue, we generated mixed chimeras which CD80/86- or CD40-deficient bone marrow-derived coexist with wild-type (WT) cells, thereby...
Malaria continues to be a major public health concern, and there are concerted efforts eliminate it. The quest for vaccine remains top priority, vaccines based on the circumsporozoite protein (CSP) among lead candidates, with RTS,S currently undergoing phase 3 testing in Africa. Previous studies have reported anti-CSP antibody–mediated enhancement of vitro invasion homologous sporozoites. This effect has been shown concentration dependent; high-level antibodies inhibitory, whereas low-level...
The mission of the NCATS Division Rare Diseases Research Innovation (DRDRI), formerly known as Office Research, is to advance rare diseases research benefit patients. DRDRI part National Center for Advancing Translational Sciences, one 27 components US Institutes Health. facilitates and coordinates NIH-wide activities involving research, well directly supporting activities. These include development maintenance a centralized database on diseases; collaboration coordination with organizations...
Malaria remains an important health threat to non-immune travelers with the explosive growth of global travel. Populations at high risk acquiring malaria infections include once semi-immune who visit friends and relatives, military forces, business international tourists destinations sub-Saharan Africa, where transmission intensity is high. Most cases have been associated poor compliance existing preventive measures, including chemoprophylaxis. High groups would benefit immensely from...
Abstract We used 5‐(and 6‐) carboxyfluorescein diacetate succinimidyl ester labeled TCR‐transgenic CD4 + T cells to investigate the contribution of B7 costimulation cell activationand clonal expansion. was blocked with fusion protein cytotoxic lymphocyte‐associated antigen‐4 (CTLA‐4)‐Ig, which prevents interaction its receptor CD28 on cells. CTLA4‐Ig had different effects depending density antigen (Ag)/MHC ligands available by In presence CTLA4‐Ig, tenfold higher concentrations Ag were...
Summary A cosmid library has been constructed from a sheep x hamster cell hybrid containing chromosome t 1 , rob (6;24). Clones DNA were identified by hybridizing to total genomic probe. Small fragments (<500 bp) (AC) n microsatellites subcloned and sequenced. Ten microsatellite markers characterized six mapped back chromosomes 6 24. The remaining 26, which was shown be present in small proportion of cells the line.
Only a small fraction of the antigens expressed by malaria parasites have been evaluated as vaccine candidates. A successful subunit will likely require multiple antigenic targets to achieve broad protection with high protective efficacy. Here we describe efficacy novel antigen, Plasmodium yoelii (Py) E140 (PyE140), against P. challenge mice. Vaccines targeting PyE140 reproducibly induced up 100% sterile in both inbred and outbred murine models. Although immunization frequency...