Andrew Bryant - US grants
Affiliations: | 2016-2019 | Psychology | Ohio University, Athens, OH, United States |
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The funding information displayed below comes from the NIH Research Portfolio Online Reporting Tools and the NSF Award Database.The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
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High-probability grants
According to our matching algorithm, Andrew Bryant is the likely recipient of the following grants.| Years | Recipients | Code | Title / Keywords | Matching score |
|---|---|---|---|---|
| 2021 | Bryant, Andrew Justin | 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. |
Role of Adam17 in Mdsc-Mediated Development of Pulmonary Hypertension @ University of Florida PROJECT SUMMARY While it is known that a reduction in leukocyte recruitment through inhibition of chemokine receptor CXCR2 attenuates development of pulmonary hypertension (PH) in murine models of disease ? and that activated pep- tidase ADAM17 levels are associated with improved vascular remodeling ? the role of ADAM17 in CXCR2- mediated myeloid cell trafficking leading to the development of PH is unknown. There is an urgent need to close this gap in knowledge because, until accomplished, immunotherapeutic modulation of myeloid-derived suppres- sor cell (MDSC) contribution to the development of pulmonary vascular disease will remain beyond reach. The overall objective of the proposed experiments is to define the contribution of ADAM17 in polymorphonuclear- MDSC (PMN-MDSC) recruitment within the lung vasculature. The central hypothesis is that reduced ADAM17 expression and activity by PMN-MDSC is necessary for recruitment of these cells to the pulmonary vasculature leading to PH. The scientific premise for this hypothesis has been formulated on the basis of preliminary data demonstrating that PMN-MDSC expressing CXCR2 are necessary for development of PH in animal models of disease, and that this circulating cell population is present to a higher degree in whole blood of IPF patients. Additionally, ADAM17 levels inversely correlate with CXCR2 expression, and are associated with development of severe PH. The rationale for the proposed research is that, upon completion of the studies it will be possible to apply current MDSC-targeted therapies to disease prevention and treatment, as well as inform potential harms in the use of ADAM17-targeted treatments for other diseases. The central hypothesis will be tested by pursuing the following specific aims: 1) test the hypothesis that ADAM17 expression and functional activity is differentially regulated in PMN-MDSC isolated from patients with PH and idiopathic pulmonary fibrosis (IPF), and 2) test the hypothesis that ADAM17 expression by PMN-MDSC protects against pathologic pulmonary vascular remodel- ing. In the first aim, peripheral blood samples from patients with IPF with and without PH will be collected, in order to define a MDSC profile in patients with disease and controls, based upon flow cytometric analysis for MDSC sub-types. Cell populations will then be characterized for allelic discrimination of an identified biomarker candidate, in addition to assessment of ADAM17 functional activity, including shedding and proteolytic activity. In the second aim, wild type and transgenic mice with deletion of ADAM17 in myeloid-derived cells (LysM.Cre- ADAM17fl/fl mice) will be used to determine the effect tissue-specific gene expression will have on the develop- ment of PH in two models of disease (bleomycin-induced pulmonary fibrosis and chronic hypoxia). Upon com- pletion, the contribution of this study will be significant because it represents a translatable strategy to improve clinical outcomes through prevention of MDSC trafficking to the lung. The proposed research is innovative be- cause it represents a substantive departure from the status quo by shifting focus from vasodilator therapy to a fine-tuned immunoregulatory mediator, MDSC, in the pathobiology of PH secondary to IPF. |
0.928 |
| 2021 | Bryant, Andrew Justin | 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. |
Role of Cxcr2-Mediated Cell Trafficking in Pulmonary Vascular Remodeling @ University of Florida PROJECT SUMMARY It is unknown how myeloid or endothelial cell expression of CXCR2 contributes to myeloid-derived suppressor cell (MDSC) recruitment to the lungs, with subsequent pulmonary vascular remodeling. There is an urgent need to close this gap in knowledge because, until accomplished, immunotherapeutic modulation of CXCR2 contribu- tion to the development of vascular remodeling, and pulmonary hypertension (PH), will likely remain beyond reach. The overall objective here is to define the contribution of MDSC recruitment through chemokine receptor CXCR2, expressed by either circulating myeloid cells or the pulmonary vascular endothelium. The central hy- pothesis is that tissue specific CXCR2 expression is necessary for polymorphonuclear (PMN)-MDSC recruitment to the pulmonary vasculature and PH development. The scientific premise for this hypothesis has been formu- lated on the basis of preliminary data demonstrating that MDSCs expressing CXCR2 are necessary for devel- opment of PH in animal models of pulmonary vascular disease, and that this circulating cell population is present to a higher degree in whole blood of idiopathic pulmonary fibrosis (IPF) patients with PH, compared to IPF pa- tients without elevated pulmonary pressures. The rationale for the proposed research is that, upon completion of experiments, future studies can be proposed taking advantage of University of Florida expertise in tissue- specific delivery of either existing CXCR2 inhibitors though use of nanoparticle technology, or CXCR2 directed gene-therapy utilizing AAV vectors. Expected outcomes, as a consequence of proposed work, are a vertical advancement in the understanding of CXCR2 contribution to vascular remodeling, additionally establishing a foundation for future studies detailing mechanisms of MDSC mediated PH development related to chronic lung disease, such as IPF. The results are expected to have positive translational impact because it is probable that the identified tissue-specific CXCR2 influence will provide targets for immunotherapeutic interventions. The cen- tral hypothesis will be tested by pursuing the following specific aims: 1) test the hypothesis that CXCR2 expres- sion by PMN-MDSC promotes development of PH, and 2) test the hypothesis that vascular endothelial cell CXCR2 expression is protective against MDSC recruitment in PH. In the first aim, wild type and transgenic mice with tissue-specific deletion of CXCR2 in myeloid-derived cells (LysM.Cre-CXCR2fl/fl, mCXCR2 mice) will be used to determine the effect that attenuated MDSC trafficking will have on the development of PH in two models of disease (bleomycin-induced pulmonary fibrosis and chronic hypoxia). In the second aim, transgenic mice with tissue-specific deletion of CXCR2 in vascular endothelial cells (VECad.Cre-CXCR2fl/fl, eCXCR2 mice) will be used in the bleomycin and hypoxia models of PH. The contribution of these studies will be significant because it represents a strategy to improve clinical outcomes through prevention of CXCR2-mediated trafficking to the lung. The proposed research is innovative because it represents a departure from the status quo by shifting focus from vasodilator therapy to an immunoregulatory mediator, MDSCs, in the pathobiology of PH. |
0.928 |