Project description:Cancer vaccines utilizing naturally circulating dendritic cell (DC) subsets, such as plasmacutoid DCs (pDCs) and type 2 convential DCs (cDC2s), have demonstrated their potential as a therapy. For melanoma in recent clinical trials. These DC vaccines aim to. human. DC subsets on the. T cell transcriptional program, which. forms the. molecular. basis. of an. antitumor. T cell response, is. poorly understood. In. this study, we investigated the eraly gene expressionsignature of CD8+ T. cells following. stimulation by pDCs or cDC2s. in. a culture system that mimics. the. current protocol of primary DC-based cancer vaccines. Our results demonstrate that pDCs and cDC2s induce a remarkably similar transcriptomic profile in CD8_ T cells, which. is tailored for increased effector function, survival and sensitivity. towards secondary signals. Nonetheless, differences between pDC- and cDC2-induced T cell gene expression signatures encompass genes with a role in proliferation, cytolytic capacity and differentiation. Combining both DC subsets results in a T cell. transcriptomic program that. is very. similar to. the program induced by. pDCs alone. The results suggest that the. choice of DC subsets for use in cancer vaccines impacts the induced antitumor CD8+ T cell response.
Project description:Corticosteroids have been prescribed for decades to modulate inflammation, yet there is a paucity of data on their effects in humans. We examined the changes in cellular and molecular immune system parameters, or âimmunome,â in 20 volunteers at baseline, and after intravenous hydrocortisone (HC) administered at moderate (250 mg) and low (50 mg) doses, to provide insight into how corticosteroids exert their effects. We observed declines in specific B and T cell subsets, and an increase in natural killer cell subsets 4-8 hours after HC. Whole transcriptome profiling revealed a gene expression signature that preceded lymphocyte population changes. We observed decreases in inflammatory cytokines after HC administration. Our study provides insights into the effects of corticosteroids on the human immunome. According to CHI protocols 11-H-0092, 18 healthy volunteers were administered a single dose of intravenous (IV) hydrocortisone at either 50 mg or 250 mg concentrations. PBMC samples were collected immediately prior to receiving the drug (0 hours), then after 1, 4, 8, 12, and 24 hours.
Project description:Corticosteroids have been prescribed for decades to modulate inflammation, yet there is a paucity of data on their effects in humans. We examined the changes in cellular and molecular immune system parameters, or “immunome,” in 20 volunteers at baseline, and after intravenous hydrocortisone (HC) administered at moderate (250 mg) and low (50 mg) doses, to provide insight into how corticosteroids exert their effects. We observed declines in specific B and T cell subsets, and an increase in natural killer cell subsets 4-8 hours after HC. Whole transcriptome profiling revealed a gene expression signature that preceded lymphocyte population changes. We observed decreases in inflammatory cytokines after HC administration. Our study provides insights into the effects of corticosteroids on the human immunome.
Project description:Infection is the most common cause of death in early life, especially for newborns and can be reduced by immunization but insufficient knowledge of how vaccines protect the very young limits their optimal use. To gain insight into how vaccines induce protection of the most vulnerable, our project employs two novel approaches studying newborn responses to hepatitis B vaccine (HBV): (a) systems biology that uses technologies which comprehensively measure global changes in molecules such as transcriptomics (RNA) and proteomics (proteins), as well as cell composition of the blood and (b) use of human newborn blood components, collected prior to immunization, to model vaccine responses in vitro (outside the body). Characterizing vaccine-induced molecular patterns (signatures) that correspond to vaccine-mediated protection will accelerate development and optimization of vaccines against early life infections of major global health importance.
Project description:Infection is the most common cause of death in early life, especially for newborns and can be reduced by immunization but insufficient knowledge of how vaccines protect the very young limits their optimal use. To gain insight into how vaccines induce protection of the most vulnerable, our project employs two novel approaches studying newborn responses to hepatitis B vaccine (HBV): (a) systems biology that uses technologies which comprehensively measure global changes in molecules such as transcriptomics (RNA) and proteomics (proteins), as well as cell composition of the blood and (b) use of human newborn blood components, collected prior to immunization, to model vaccine responses in vitro (outside the body). Characterizing vaccine-induced molecular patterns (signatures) that correspond to vaccine-mediated protection will accelerate development and optimization of vaccines against early life infections of major global health importance.
Project description:This project is part of the Malaria Host-Pathogen Interaction Center (MaHPIC) - a transdisciplinary malaria systems biology research program initially supported by an NIH/NIAID contract (# HHSN272201200031C, 2012-2017; see http://www.systemsbiology.emory.edu). The MaHPIC continues with ongoing support from the Defense Advanced Research Project Agency (DARPA) and others. The MaHPIC generates many data types (e.g., clinical, hematological, parasitological, metabolomics, functional genomics, lipidomics, proteomics, immune response, telemetry) and mathematical models, to iteratively test and develop hypotheses related to the complex host-parasite dynamics in the course of malaria in non-human primates (NHPs), and metabolomics data via collaborations with investigators conducting clinical studies in malaria endemic countries, with the overarching goal of better understanding human disease, pathogenesis, and immunity. Curation and maintenance of all data and metadata are the responsibility of the MaHPIC: Mary Galinski mary.galinski@emory.edu (MaHPIC Program Director), Jessica Kissinger jkissinger@uga.edu (MaHPIC Co-Program Director), and Alberto Moreno alberto.moreno@emory.edu (MaHPIC Co-Program Director).
Project description:This project is part of the Malaria Host-Pathogen Interaction Center (MaHPIC) - a transdisciplinary malaria systems biology research program initially supported by an NIH/NIAID contract (# HHSN272201200031C, 2012-2017; see http://www.systemsbiology.emory.edu). The MaHPIC continues with ongoing support from the Defense Advanced Research Project Agency (DARPA) and others. The MaHPIC generates many data types (e.g., clinical, hematological, parasitological, metabolomics, functional genomics, lipidomics, proteomics, immune response, telemetry) and mathematical models, to iteratively test and develop hypotheses related to the complex host-parasite dynamics in the course of malaria in non-human primates (NHPs), and metabolomics data via collaborations with investigators conducting clinical studies in malaria endemic countries, with the overarching goal of better understanding human disease, pathogenesis, and immunity. Curation and maintenance of all data and metadata are the responsibility of the MaHPIC: Mary Galinski mary.galinski@emory.edu (MaHPIC Program Director), Jessica Kissinger jkissinger@uga.edu (MaHPIC Co-Program Director), and Alberto Moreno alberto.moreno@emory.edu (MaHPIC Co-Program Director).