Goal 2: Reduce Human Disease

Research on in vitro and in vivo Biomarker Predictors of Clinical Response in Lung Disease

How can research on in vitro and in vivo biomarker predictors of clinical response in lung disease be encouraged?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea Cystic Fibrosis Foundation

Voting

2 net votes
5 up votes
3 down votes
Active

Goal 1: Promote Human Health

Combinatorial intervention of immune dynamics to combat cariovascular disease

Human health and disease are modulated by complex and inter-connected dynamic processes. With particular significance, a well-balanced immune environment may play a key role in maintaining health and preventing the pathogenesis of cardiovascular disease. Defining the dynamic programming and balance of immune environment will be the key for combinatorial therapies to reset homeostasis.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Name of idea submitter and other team members who worked on this idea Liwu Li

Voting

8 net votes
10 up votes
2 down votes
Active

Goal 4: Develop Workforce and Resources

Increase and Support Research Based Faculty

As the current chair of the Research and Training Division, I would like to convey that the AAAAI membership would like the NHLBI to consider the following in the development of its strategic plan:

There has been a decline in research-based faculty in the past few years.  The challenge is two-fold.  First, increase the research faculty pipeline with increased focus on training and recruitment of research focused fellows... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Name of idea submitter and other team members who worked on this idea Mitchell Grayson on behalf of the American Academy of Allergy, Asthma, and Immunology

Voting

59 net votes
76 up votes
17 down votes
Active

Goal 2: Reduce Human Disease

A Systems Approach to Obesity

There is a need to use an integrated systems approach to obesity prevention and treatment. Obesity is a complex phenotype influenced by factors from the molecular to the socio-economic level. To address the causes and prevention of obesity, we need to integrate information at the molecular level with behavioral, social and environmental data. This will require investigators in molecular biology, genetics, epidemiology,... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Addressing this critical challenge will enable scientists and clinicians to move beyond the identification of singular risk factors for obesity to develop a holistic approach to prevention and treatment of this critical health problem.

Feasibility and challenges of addressing this CQ or CC

The molecular technology, environmental monitoring technology, analytic and bioinformatics infrastructure are sufficiently developed to generate the necessary data and analyze disparate data types within the larger systems biology framework.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

Voting

97 net votes
138 up votes
41 down votes
Active

Goal 3: Advance Translational Research

Can hair follicle stem cells be transformed into new cells or organs?

Dr. Cotsarelis of the Univ. of Pennsylvania identified the bulge area of the hair follicle, which is now thought to contain the hair's stem cells. These cells would seem to be readily available and unique to an individual person. Can further work be done to transform these cells into now only hair cells but other organ tissues?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Voting

-15 net votes
5 up votes
20 down votes
Active

Goal 2: Reduce Human Disease

UNDERSTANDING PROGRESSIVE FIBROTIC DISEASES TO IDENTIFY NEW THERAPEUTIC TARGETS

Our understanding of the factors driving IPF fibrotic progression remain incompletely understood. To develop effective therapies that arrest and reverse the fibrotic process, we must first identify the critical factors driving the spread of fibrosis. Fibroblastic foci, the sentinel morphologic lesion of IPF, are found at the advancing edge of fibrosis. Fibroblastic foci can be conceptualized as a fibrotic niche. The... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Technologically advanced descriptive studies to create a comprehensive fibroblastic focus atlas are a necessary first step to understand fibrotic progression. The atlas will include: 1) The identification and number of each the cell type in the focus and their interplay. There is considerable heterogeneity among the mesenchymal cells and inflammatory cells within the focus and innovative single cell OMICs technology will be required to define disease-relevant subpopulations of each cell type within the focus. This work requires laser caption microdissection, immunohisotchemical and in situ hybridization techniques to map the location of various cell types within the fibroblastic focus. 2) Extracellular matrix composition and mechanical properties. Currently it is unclear whether the fibroblastic focus is topographically polarized. For example, it is conceivable that the focus may be polarized with cell-dense regions consisting of various cell types in a provisional/wound-like matrix juxtaposed to less cellular regions consisting of more mature mesenchymal cells in a collagen rich matrix. 3) Cytokine levels and oxygen tension. There is a large and expanding literature in several biomedical disciplines that each of these characteristics matter; influencing differentiation, proliferation, metabolism, and migration. Lacking all of these data, it is not surprising that IPF has been such a difficult problem to solve.

Feasibility and challenges of addressing this CQ or CC

Since these will be highly innovative, yet descriptive – funding them through investigator initiated awards reviewed by standing study section is not feasible. They will employ novel emerging techniques including single cell RNA sequencing and single cell mass cytometry to identify heterogeneous cell populations, state of the art proteomic techniques to define matrix composition and cytokine levels within the fibroblastic focus, and atomic force microscopy to map stiffness across the fibroblastic focus. When considering applications, an RFA mechanism makes sense (perhaps a U-series granting mechanism) where the standard criteria are used for review, but innovation accounts for 75% of the total priority score. The idea is that the reviewers’ discussion and score will be heavily weighted towards innovation, i.e. really new ideas or approaches with less emphasis on a detailed critique of the methods to be employed, and the impact of the project in advancing knowledge. Therefore, convening a Special Emphasis Panel (SEP) that is instructed to identify the most highly innovative, high impact projects would be ideal.

Name of idea submitter and other team members who worked on this idea Craig Henke and Peter Bitterman

Voting

-1 net votes
12 up votes
13 down votes
Active

Goal 1: Promote Human Health

Study wellness instead of diseases by longitudinal follow-up of frequent and long term blood donors

Blood donors (especially young donors) in general represent healthy populations. Longitudinal follow-up of frequent and long term blood donors can be useful to establish data and sample sources for the study of wellness, instead of disease (especially for blood diseases). Not only it can be used as healthy controls, it can also be used to predict the wellness factors such as genetic variation, life style, exercise patterns,... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Once such study is established, it can be used as a wellness model/control for many diseases and conditions. The longer we have the study, more useful it will become. This can help us to change or optimize our health care model, from treating diseases to maintain wellness.

Feasibility and challenges of addressing this CQ or CC

This can be quite feasible as there are many frequent and long term donors. They care about others’ health as well as their own health. They are also very willing to support research. Follow-up can start from early adulthood.

With funding support this can be achieved.

Name of idea submitter and other team members who worked on this idea Yanyun Wu

Voting

2 net votes
2 up votes
0 down votes
Active

Goal 2: Reduce Human Disease

Clinical trials of AAT augmentation therapy

Alpha-1 antitrypsin augmentation therapy is widely used for PI ZZ subjects, but randomized clinical trials of AAT augmentation therapy have not been adequately powered to assess the efficacy of this treatment. A clinical trial using COPD exacerbation frequency as the primary outcome, rather than decline in lung function, in PI ZZ subjects with moderate-to-severe COPD could provide definitive evidence for the utility of... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Name of idea submitter and other team members who worked on this idea American Thoracic Society member

Voting

1 net vote
1 up votes
0 down votes
Active

Goal 3: Advance Translational Research

Applying Imaging in Chronic Lung Diseases

How can chest CT or other imaging tools be optimally used to characterize expression and progression of chronic lung disease?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Chest CT scans provide anatomical information on disease pattern and severity that cannot be readily obtained otherwise. These imaging studies could be essential in reclassifying chronic lung diseases more effectively and in assessing disease progression more accurately.

Feasibility and challenges of addressing this CQ or CC

The increasing use of chest CT scans for lung cancer screening will provide a large number of imaging studies that could transform pulmonary research in multiple chronic lung diseases. However, the images will need to be appropriately collected and analyzed.

Name of idea submitter and other team members who worked on this idea Ed Silverman, James Crapo and COPDGene Executive Committee

Voting

33 net votes
47 up votes
14 down votes
Active

Goal 3: Advance Translational Research

Developing Methods and Metrics for T4 Outcomes and Impact

How can methods and metrics capable of conducting high quality T4 research be developed to accurately capture outcomes and the overall impact new T4 knowledge has on population health for heart, lung, blood, sleep diseases and disorders?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

High quality T4 research methods and metrics are needed to move the field of T4 translation research forward while linking large data sets from different sources.

Feasibility and challenges of addressing this CQ or CC

Demand for high quality methods, metric and evaluation of T4 translation research interest is growing and needs to be addressed immediately to move the field forward.
Recent IOM/NRC studies recommended that the NIH and other research funding agencies support the development of more refined analytic methods and study designs for cross-national health research. These methods should include innovative study designs, creative uses of existing data, and novel analytical approaches to better elucidate the complex causal pathways. The T4 field has some specific metrics including acceptability, reach, adoption, appropriateness, feasibility, fidelity, cost, penetration, and sustainability, each with its standard measurement approach. In addition to a rigorous study design, including these metrics along with population level impact direct measures (e.g., morbidity, mortality) and intermediate measures (e.g. blood pressure reduction) will be critical to assess what has been accomplished and to define success. Finally, measuring the overall impact of new knowledge generated from T4 research is challenging because publication bibliometrics of high impact scholarly journals may not fully capture it.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

Voting

-1 net votes
7 up votes
8 down votes
Active

Goal 2: Reduce Human Disease

2. Mechanism and target identification for abnormal epigenetic regulation in cardiovascular disease

Abnormal epigenetic modification has been implicated in human disease. Epigenetic therapy using nonspecific inhibitors for histone acetylation and DNA methylation has been proved effective in some cancer. However, because histone acetylation and DNA methylation are essential biochemical modification of life process, globally suppression on these process would have severe adverse effect. Identification of specific mechanism... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Name of idea submitter and other team members who worked on this idea Hong Wang, Xiaofeng Yang

Voting

34 net votes
34 up votes
0 down votes
Active

Goal 3: Advance Translational Research

Is the current scoring system working? Should it be changed?

Score compression is a major problem for identifying the most meritorious applications. Compression is facilitated by the reduced availability of scoring alternatives for the reviewers. Why not increase the range of numbers that can be used for voting (e.g., use decimals in the scoring)?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Voting

-6 net votes
9 up votes
15 down votes
Active

Goal 2: Reduce Human Disease

How do Cell Therapies Really Work?

Multiple lines of evidence suggest that the beneficial effects of cell therapy are mostly indirect, but what are the key factors responsible for these indirect benefits?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Could restore lost or diminished organ function

Feasibility and challenges of addressing this CQ or CC

Extensive research infrastructure already exists and durability and quality of beneficial effects has continued to increase over time, although incrementally. Field is poised for a breakthrough with the right spark funding.
Cell-based therapies, demonstrated with a wide range of cell types, have shown glimmers of promise in HLB applications, such as improved functional recovery, reduced scar formation, and beneficial effects up to 6 months. However, transplanted cells have poor retention, minimal long-term survival, and the mechanism-of-action is unclear.

 

The challenge is to stimulate new hypotheses on the mechanism-of-action in order to achieve long-term benefits, and then to support definitive confirmatory studies. Funding already exists, but the main spark might come from encouraging other disciplines to get involved.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

Voting

-1 net votes
18 up votes
19 down votes
Active

Goal 2: Reduce Human Disease

Sublingual Immunotherapy for Treatment of Asthma

As the current chair of the Research and Training Division, I would like to convey that the AAAAI membership would like the NHLBI to consider the following in the development of its strategic plan: What role should sublingual immunotherapy play in the treatment of asthma?


Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea Mitchell Grayson on behalf of the American Academy of Allergy, Asthma, and Immunology

Voting

-9 net votes
5 up votes
14 down votes
Active

Goal 2: Reduce Human Disease

Developing techniques to monitor neurologic injury after cardiac arrest

Can techniques to monitor brain injury and recovery in post-cardiac arrest patients be developed to optimize post-cardiac arrest care and enable reliable neuroprognostication?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea AHA Staff & Volunteers

Voting

-1 net votes
2 up votes
3 down votes
Active