1992 — 1996 |
Scott, Alan L |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
B Malayi L3/L4 Surface Antigens From Pcr Cdna Libraries @ Johns Hopkins University
Over 900 million people are at risk of acquiring lymphatic filariasis and it has been estimated that over 90 million are currently infected with Wuchereria bancrofti, Brugia malayi, or B. timori. The long-term objective of this study is to determine the molecular basis for protective immunity against filarial nematode parasites employing B. malayi as a model system. In these studies, we propose to focus our efforts on the proteins associated with the surface of the L3 and L4 stages of the parasite. Employing surface and metabolic labeling procedures and immunochemical analyses, we will characterize the composition and the time of synthesis of the major surface-associated components of the early infective forms of B. malayi. L3 surface-associated antigens will be characterized from larvae undergoing microfilaria-L2-L3 development in vivo in the mosquito vector. L4 surface-associated antigens will be studied in larvae undergoing L3-L4 development either in in vitro culture or in chambers implanted in a vertebrate host. The information on the composition and the interval of synthesis will be used to efficiently employ an innovative adaptation of the polymerase chain reaction (PCR) in a strategy to clone these surface constituents. In this adaptation of the PCR, the entire population of larval CDNAS are amplified in a procedure that results in the production of large amounts of larval PCRcDNAs all of which contain. restriction enzyme sites on the 5' and 3' ends so that the PCRcDNA products can be directionally cloned into a vector to form PCRcDNA libraries. Immunoscreening of PCRcDNA libraries will be carried out to identify and clone sequences encoding surface-associated molecules from B. malayi L3s and L4s. After characterizing the cloned DNAs and their protein products, the recombinant larval antigens will be expressed and used in a B. malayi-animal model system to test for their ability to induce protection against parasite challenge. In addition to providing information on the basic biology and biochemistry of the larval forms of this parasite, this study will provide recombinant reagents for the identification and study of the immune effector mechanisms that mediate protection against filarial infection.
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0.955 |
1999 — 2003 |
Scott, Alan L |
P60Activity Code Description: To support a multipurpose unit designed to bring together into a common focus divergent but related facilities within a given community. It may be based in a university or may involve other locally available resources, such as hospitals, computer facilities, regional centers, and primate colonies. It may include specialized centers, program projects and projects as integral components. Regardless of the facilities available to a program, it usually includes the following objectives: to foster biomedical research and development at both the fundamental and clinical levels; to initiate and expand community education, screening, and counseling programs; and to educate medical and allied health professionals concerning the problems of diagnosis and treatment of a specific disease. |
Core--Molecular @ Johns Hopkins University
The Molecular and Technology TRANSFER Core will provide Center for Craniofacial Development and Disorders. Investigators with access to modern molecular genetics services including DNA synthesis, DNA sequencing, mutation detection, DNA isolation, cell culture, lymphocyte transformation, cryopreservation, physical mapping regents and specific YAC clones. This core will also assist investigators evaluate technologies developed in their studies for commercial licensing and patentability. The Molecular and Technology Transfer Core will provide reagents and services for the Clinical ore and Projects I, II, V, VI and VII. It will also advise Projects I and II involved in animal models; Projects III and VI concerned with therapeutics for craniosynostosis; Projects V, VI and VII developing DNA diagnostic testing; and Project VIII regarding behavioral and psychological services. This Core will monitor and enhance the ability of the Center to develop potentially marketable products and other effective interventions.
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0.955 |
2000 — 2003 |
Scott, Alan L |
U01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Applied Genomics in Cardiopulmonary Disease @ Johns Hopkins University
The overall goal of the Animal/Proteomic Component of the "Applied Genomic Program in Cardiopulmonary Disease" is to define and test the relevance of disease specific gene candidates that predict lung and cardiac remodeling in animal models of cardiopulmonary diseases utilizing gene profiling approaches. Identification of susceptibility genes for human disease is hampered by variability in clinical phenotype, genetic heterogeneity in human populations and the experimental difficulty in addressing the molecular mechanisms underlying complex pathological processes in humans. Thus our strategy is to take advantage of the experimental tractability of murine models of disease to provide high quality of candidate genes underlying remodeling processes in multiple cardiopulmonary disease. To achieve this goal, we have assembled an outstanding group of investigators with broad and overlapping expertise with animal models of cardiopulmonary diseases including asthma, pulmonary fibrosis, cardiac failure, emphysema, hyperoxia-induced lung injury and pulmonary hypertension. Our preliminary data suggest that these models are predictive of human disease and that the gene profiling approach can successfully be used to identify genes important in human disease. The specific aims of this component are l) to define a set of predictor genes for tissue remodeling using Affymetrix 5000 predictor oligonucleotide microarrays (Mu19K) in each of the six animal models of disease; 2) to refine the number of candidate genes and to establish the kinetics of gene expression by constructing custom cDNA arrays for 1000-5000 predictor genes in each model; and 3) to compare and contract gene expression profiles between models and human systems in order to prioritize candidates for further analysis by proteomic and single nucleotide polymorphism (SNPs) approaches; 4) to utilize proteomic approaches to study the consequences of changes in gene expression at the cell and tissue level; and 5) to being to determine the functional relevance of this focused set of genes to remodeling processes by utilizing transgenic and knockout technologies. The combined (mouse and human) approach of this program to the identification of disease specific genes for lung and cardiac remodeling should greatly facilitate future disease discovery.
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0.955 |
2010 — 2014 |
Scott, Alan L |
U19Activity Code Description: To support a research program of multiple projects directed toward a specific major objective, basic theme or program goal, requiring a broadly based, multidisciplinary and often long-term approach. A cooperative agreement research program generally involves the organized efforts of large groups, members of which are conducting research projects designed to elucidate the various aspects of a specific objective. Substantial Federal programmatic staff involvement is intended to assist investigators during performance of the research activities, as defined in the terms and conditions of award. The investigators have primary authorities and responsibilities to define research objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations and conclusions of their studies. Each research project is usually under the leadership of an established investigator in an area representing his/her special interest and competencies. Each project supported through this mechanism should contribute to or be directly related to the common theme of the total research effort. The award can provide support for certain basic shared resources, including clinical components, which facilitate the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence. |
Genomics and Genotyping Core @ Johns Hopkins University
The goal of Core 3 (Genotyping) is to provide the infrastructure and technical expertise required to carryout the genetic-based studies proposed in the ICEMR. Core 3 will take advantage ofthe instrument infrastructure and the seven years of experience and expertise established by the Johns Hopkins Malaria Research Institute. Core 3 will provide services for the ICEMR investigators to generate high-quality genotyping, genomics and expression data using microarray, PCR and sequencing platforms. The Core will provide genotyping analysis of mosquito samples using PCR and lllumina platforms. Parasite samples will be genotyped employing the Affymetrix GeneChip and real time PCR platforms. Samples from human participants will be analyzed for multiplicity of infection using a nested PCR-based approach. Core 3 will facilitate in the analysis, interpretation and the integration ofthe data into the ICEMR database.
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0.955 |
2010 — 2011 |
Agre, Peter C (co-PI) [⬀] Bream, Jay H. Coppens, Isabelle Dimopoulos, George (co-PI) [⬀] Dinglasan, Rhoel David Ramos (co-PI) [⬀] Glass, Gregory E (co-PI) [⬀] Griffin, Diane E [⬀] Hardwick, J. Marie Hoiczyk, Egbert (co-PI) [⬀] Jacobs-Lorena, Marcelo (co-PI) [⬀] Ketner, Gary W (co-PI) [⬀] Klein, Sabra L (co-PI) [⬀] Kumar, Nirbhay (co-PI) [⬀] Levitskaia, Elena Margolick, Joseph B. (co-PI) [⬀] Markham, Richard B. (co-PI) [⬀] Moss, William J (co-PI) [⬀] Norris, Douglas E Pekosz, Andrew S. Pineda, Fernando Javier Prigge, Sean Taylor (co-PI) [⬀] Rasgon, Jason L (co-PI) [⬀] Rose, Noel R. (co-PI) [⬀] Scott, Alan L Shiff, Clive J (co-PI) [⬀] Yu, Xiao-Fang (co-PI) [⬀] Zavala, Fidel P (co-PI) [⬀] Zhang, Ying (co-PI) [⬀] Zhang, Ying (co-PI) [⬀] Zhang, Ying (co-PI) [⬀] Zhang, Ying (co-PI) [⬀] |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Training: Molecular &Cellular Bases of Infectious Diseases @ Johns Hopkins University
DESCRIPTION (provided by applicant): Continued training in The Molecular and Cellular Bases of Infectious Diseases (MCBID) is proposed for 8 PhD students and 3 postdoctoral fellows selected from large pools of highly qualified applicants. The training program is uniquely situated in the Molecular Microbiology and Immunology Department (MMI) within the Johns Hopkins Bloomberg School of Public Health. The 29 training faculty have a wide range of experience and expertise in viruses, bacteria and parasites causing human disease and in the vectors and environmental factors associated with emergence and transmission of these pathogens. The training program has been funded since 1994 and has produced scientists working in many areas of academia and government on problems related to infectious diseases, vaccine development and the public's health. The goal of the MCBID training program is to provide students with both a firm foundation in the basic disciplines necessary for the study of infectious diseases and a perspective that will enable them to apply their knowledge creatively to public health problems. Each student is expected to complete 1) a series of required courses in the basic disciplines of cell and molecular biology, biochemistry, and immunology, 2) courses in virology, bacteriology, parasitology, and disease ecology, 3) courses in research ethics and public health perspectives, and 4) elective courses relevant to thesis topic and long-term career goals. Elective courses are chosen from among courses available in MMI, other departments in the School of Public Health, or in other Divisions of the University. Students will also complete 3 11-week laboratory rotations during the first year. Student progress is monitored by a Thesis Advisory Committee and the Graduate Program Committee. The goals of the postdoctoral training program are 1) to provide focused training in those areas of the molecular and cellular basis of infectious diseases in which program faculty have special expertise;2) to provide an opportunity for doctoral degree holders trained in more traditional environments to broaden their exposure to problems of public health importance and to evaluate their career goals in terms of public health issues;and 3) to prepare the PDF for an independent career in the biological sciences. RELEVANCE : This program is highly relevant to national interests in the areas of emerging infectious diseases, as it trains students and postdoctoral fellows broadly not only in both the molecular aspects of pathogen biology and disease pathogenesis, but also in the ecology of disease emergence and the role of vectors in pathogen transmission.
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0.955 |
2012 — 2014 |
Agre, Peter C (co-PI) [⬀] Bream, Jay H. Coppens, Isabelle Dimopoulos, George (co-PI) [⬀] Dinglasan, Rhoel David Ramos (co-PI) [⬀] Glass, Gregory E (co-PI) [⬀] Griffin, Diane E [⬀] Hardwick, J. Marie Hoiczyk, Egbert (co-PI) [⬀] Jacobs-Lorena, Marcelo (co-PI) [⬀] Ketner, Gary W (co-PI) [⬀] Klein, Sabra L (co-PI) [⬀] Kumar, Nirbhay (co-PI) [⬀] Levitskaia, Elena Margolick, Joseph B. (co-PI) [⬀] Markham, Richard B. (co-PI) [⬀] Moss, William J (co-PI) [⬀] Norris, Douglas E Pekosz, Andrew S. Pineda, Fernando Javier Prigge, Sean Taylor (co-PI) [⬀] Rasgon, Jason L (co-PI) [⬀] Rose, Noel R. (co-PI) [⬀] Scott, Alan L Shiff, Clive J (co-PI) [⬀] Yu, Xiao-Fang (co-PI) [⬀] Zavala, Fidel P (co-PI) [⬀] Zhang, Ying (co-PI) [⬀] Zhang, Ying (co-PI) [⬀] Zhang, Ying (co-PI) [⬀] Zhang, Ying (co-PI) [⬀] |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Training: Molecular & Cellular Bases of Infectious Diseases @ Johns Hopkins University
DESCRIPTION (provided by applicant): Continued training in The Molecular and Cellular Bases of Infectious Diseases (MCBID) is proposed for 8 PhD students and 3 postdoctoral fellows selected from large pools of highly qualified applicants. The training program is uniquely situated in the Molecular Microbiology and Immunology Department (MMI) within the Johns Hopkins Bloomberg School of Public Health. The 29 training faculty have a wide range of experience and expertise in viruses, bacteria and parasites causing human disease and in the vectors and environmental factors associated with emergence and transmission of these pathogens. The training program has been funded since 1994 and has produced scientists working in many areas of academia and government on problems related to infectious diseases, vaccine development and the public's health. The goal of the MCBID training program is to provide students with both a firm foundation in the basic disciplines necessary for the study of infectious diseases and a perspective that will enable them to apply their knowledge creatively to public health problems. Each student is expected to complete 1) a series of required courses in the basic disciplines of cell and molecular biology, biochemistry, and immunology, 2) courses in virology, bacteriology, parasitology, and disease ecology, 3) courses in research ethics and public health perspectives, and 4) elective courses relevant to thesis topic and long-term career goals. Elective courses are chosen from among courses available in MMI, other departments in the School of Public Health, or in other Divisions of the University. Students will also complete 3 11-week laboratory rotations during the first year. Student progress is monitored by a Thesis Advisory Committee and the Graduate Program Committee. The goals of the postdoctoral training program are 1) to provide focused training in those areas of the molecular and cellular basis of infectious diseases in which program faculty have special expertise; 2) to provide an opportunity for doctoral degree holders trained in more traditional environments to broaden their exposure to problems of public health importance and to evaluate their career goals in terms of public health issues; and 3) to prepare the PDF for an independent career in the biological sciences. RELEVANCE : This program is highly relevant to national interests in the areas of emerging infectious diseases, as it trains students and postdoctoral fellows broadly not only in both the molecular aspects of pathogen biology and disease pathogenesis, but also in the ecology of disease emergence and the role of vectors in pathogen transmission.
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0.955 |
2018 — 2021 |
Mitzner, Wayne [⬀] Scott, Alan L |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Mechanism of Pathogenic Macrophage Activation in Emphysema @ Johns Hopkins University
Mechanism of pathogenic macrophage activation in emphysema Summary Chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death in the U.S. and its prevalence is increasing globally. Emphysema, a key component of COPD most commonly associated with cigarette smoking, is defined by an irreversible loss of lung surface area and decrements in gas exchange that arise from progressive alveolar wall destruction. While elements that contribute to the initiation and pathogenesis of emphysema have been identified, including recurrent inflammation, oxidative stress, excess protease activity, cell death and genetics, we still lack clear mechanisms that would provide novel targets to slow or stop disease progression during or after smoking cessation. In this proposal, we have identified a novel role for pathologic macrophages in causing the progressive damage in emphysema. Strong preliminary data shows that IL-33 remains elevated in the lung after acute lung damage and is associated with an increase in Pathogenic Lung Macrophages (PLM) that have an altered M2 phenotype. Furthermore, our data also suggest that IL-17A is critical for this transition into PLM that work against the normal healing function of M2 macrophages. Although both IL-17A and IL-33 have been found in patients with COPD, little is known about how they impact the mechanism of progressive tissue destruction. Experiments will test a novel 2-step mechanism for lung macrophage activation in which IL-33 and IL-13, generated as a consequence of epithelial cell damage, initially result in conventional M2 activation, followed by second signal from IL-17A that modifies the macrophages to the PLM that mediate alveolar destruction. Our proposal is designed to test the central hypothesis that IL-33, IL-13 and IL-17A work together to promote the generation of pathogenic lung macrophages that play a principal role in progressive emphysema. Once the basic mechanisms are better understood in our first two aims, the third aim will test the hypothesis that the known plasticity of macrophages can be exploited to devise a therapeutic strategy to blunt or stop the progression of emphysema. The insights obtained from these studies should provide novel mechanistic insights and new potential therapeutic targets to limit the accelerated loss of lung function in humans with COPD.
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0.955 |