Overall Impact Numerical Score: 3
Overall Evaluation: This is a competitive renewal application on Poultry Dust and Lung Inflammation form an established investigator. The renewal application builds on the discoveries made in the last funding cycle on effects of poultry dust on lung epithelial cells and monocytic cells, and lung inflammation in a mouse model. The data showed that poultry dust contains protease activity, induces robust inflammatory gene expression in lung epithelial and monocytic cells and activation of protease-activated receptors (PARs)-mediated cell signaling may be responsible for the elaboration of inflammatory gene expression. The data also showed …show more content…
• The proposal plans not only to elucidate mechanistic details on how poultry dust induces lung inflammation, but also investigates whether blocking one or more of these signaling pathways by specific compound could block the dust-induced inflammation.
Weaknesses
• Although the each aim is focused on addressing a specific hypothesis, there is no central hypothesis. It is unclear how the PAR activation-induced STAT3 signaling fits with the oxidative stress-induced signaling in poultry dust-induced lung inflammation.
• Aim 4, which determines the effect of poultry dust exposure on influenza A infection-associated lung inflammation and dysfunction, deviates from the primary focus of the application.
SCORED REVIEW CRITERIA
Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each.
1. Significance Numerical Score: 2: …show more content…
Therefore, investigating the role of PARs in the dust-inducted inflammation is highly appropriate. The methodology is straightforward.
• The observations that dust extract induces STAT3 activation and PAR1 inhibitor reduces the dust extract-induced STAT3 phosphorylation make a good connection between PAR1 STAT3 activation in mediating dust extract-induced lung inflammation. The preliminary data showing Stattic completely attenuates dust extract-induced cytokine expression make is highly suitable to test its effect in the animal model system.
• The preliminary studies showing that dust exposure induces the oxidant stress and the antioxidant CDDOIm inhibits the dust extract-induced cytokine expression strengthens the studies proposed in Aim 3. Determining the effect of dust exposure on mitochondria function and electron chain may provide clues how the dust exposure induces oxidant stress.
Weaknesses
• Potential difficulties and alternative experiments were not described
Overall Evaluation: This is a competitive renewal application on Poultry Dust and Lung Inflammation form an established investigator. The renewal application builds on the discoveries made in the last funding cycle on effects of poultry dust on lung epithelial cells and monocytic cells, and lung inflammation in a mouse model. The data showed that poultry dust contains protease activity, induces robust inflammatory gene expression in lung epithelial and monocytic cells and activation of protease-activated receptors (PARs)-mediated cell signaling may be responsible for the elaboration of inflammatory gene expression. The data also showed …show more content…
• The proposal plans not only to elucidate mechanistic details on how poultry dust induces lung inflammation, but also investigates whether blocking one or more of these signaling pathways by specific compound could block the dust-induced inflammation.
Weaknesses
• Although the each aim is focused on addressing a specific hypothesis, there is no central hypothesis. It is unclear how the PAR activation-induced STAT3 signaling fits with the oxidative stress-induced signaling in poultry dust-induced lung inflammation.
• Aim 4, which determines the effect of poultry dust exposure on influenza A infection-associated lung inflammation and dysfunction, deviates from the primary focus of the application.
SCORED REVIEW CRITERIA
Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each.
1. Significance Numerical Score: 2: …show more content…
Therefore, investigating the role of PARs in the dust-inducted inflammation is highly appropriate. The methodology is straightforward.
• The observations that dust extract induces STAT3 activation and PAR1 inhibitor reduces the dust extract-induced STAT3 phosphorylation make a good connection between PAR1 STAT3 activation in mediating dust extract-induced lung inflammation. The preliminary data showing Stattic completely attenuates dust extract-induced cytokine expression make is highly suitable to test its effect in the animal model system.
• The preliminary studies showing that dust exposure induces the oxidant stress and the antioxidant CDDOIm inhibits the dust extract-induced cytokine expression strengthens the studies proposed in Aim 3. Determining the effect of dust exposure on mitochondria function and electron chain may provide clues how the dust exposure induces oxidant stress.
Weaknesses
• Potential difficulties and alternative experiments were not described