Goal 1: Promote Human Health

Transforming Transplantation with Reprogramming Immune System Cells (RISC)

Can we "reprogram" the immune system to improve outcomes of heart, lung, and hematopoietic cell transplants? While NIAID is a major funder of immunology research, we are a major contributor to stem cell research. Our resources could be combined, where NIAID would support this approach for autoimmune diseases, and we would support work in tolerance for transplants. If the NCI also wants to collaborate on co-stimulatory ...more »

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

This innovative and transformative proposal could improve tolerance to many different types of transplants.

Feasibility and challenges of addressing this CQ or CC :

In 2002, Hochedlinger and Jaenisch (Nature 415:1035-1038) created a mouse by nuclear transplantation from a mature B-cell. This was proof of principle that the immune system can be reprogrammed entirely. Since then there has been little work in this area, but Reprogramming Immune System Cells (RISC) is risky but promising.

A second approach involves mechanisms that cancer cells use to evade immune detection. While most cancer research works to restore immune competence for therapy, the basic biology of evading immune detection could be exploited to improve tolerance. These approaches could be tested in an animal model in 5 years.

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

Voting

15 net votes
27 up votes
12 down votes
Active

Goal 2: Reduce Human Disease

Behavior change labs: an interdisciplinary team approach

Will integration of behavior science in clinical research improve effectiveness of interventions for HLBS diseases associated with behavioral risk factors?

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

Currently, there is no industry support for T1 (basic to clinical) behavioral research and therefore little incentive for basic and clinical behavioral scientists to work together to develop and test new, innovative strategies for changing HLBS-related behaviors based on basic behavioral science findings on motivation, perception, cognition and social relationships. Bringing together collaborative, interdisciplinary teams of basic behavioral scientists and clinically-oriented behavioral researchers could spur development and testing of innovative new approaches to difficult HLBS-related behavioral problems such as obesity, unhealthy diets, sedentary lifestyles, smoking and non-adherence to preventive and therapeutic HLBS regimens.

Feasibility and challenges of addressing this CQ or CC :

New research in the behavioral sciences is elucidating the basic psychological, cognitive, social and behavioral processes underlying behavior and behavior change. Findings in this area could be developed into new strategies targeting problematic HLBS-related behaviors, but a mechanism for developing and testing novel ideas is needed. Networks designed to bring together basic and clinically-oriented behavioral researchers can enable better understanding of the bases of HLBS-related behaviors and accelerate the translation of findings into new approaches.

Adopting and maintaining healthy habits and lifestyles – such as eating healthy diets, engaging in regular physical activity, stopping smoking, and regularly taking prescribed medications – are crucial to heart, lung, blood and sleep (HLBS) health (Akesson et al, 2014; Mozaffarian, 2014). However, for most people, engaging in and maintaining a healthy lifestyle is challenging. Interventions designed to promote behavior change have had limited success, often influencing individuals over the short-term but failing to alter behaviors over longer periods of time, which is necessary to realizing the full benefits of a healthy lifestyle. Underlying the problematic behaviors associated with HLBS-related behavioral risk factors are fundamental psychological, motivational, cognitive and social processes that represent promising targets for the development of new, more effective behavioral interventions. For example, basic behavioral scientists are investigating the role of poor executive function in unhealthy eating behavior and exploring new ways to address the "self-control" failures that lead to impulsive eating.

 

However, unlike the biomedical arena where the translational pathway from basic science to clinical application is supported by both NIH and industry, there is no industry support and relatively little NIH funding devoted to T1 behavioral research -- i.e., research translating basic behavioral science findings into clinically significant behavioral interventions. As a result, basic behavioral science researchers have little incentive to collaborate with clinical researchers to develop and test novel behavioral treatments. Bringing together collaborative, interdisciplinary teams of basic behavioral scientists and clinically-oriented behavioral researchers could spur development and testing of innovative new approaches to difficult HLBS-related behavioral problems.

 

A compelling question is how to bring together these disparate researchers over a long enough time frame to enable them to identify, develop and testing new strategies for tackling resistant behavioral problems. One way to address this question is to fund a network of "behavior change labs," each of which brings together teams of basic behavioral scientists who are investigating the bases of behavior and behavior change with clinical researchers interested in designing, optimizing and testing novel ideas for tackling the difficult behavioral problems represented by obesity, unhealthy diets, sedentary lifestyles, smoking and non-adherence to medications used to prevent or treat HLBS diseases and disorders.

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

Voting

83 net votes
129 up votes
46 down votes
Active

Goal 2: Reduce Human Disease

Congential heart defects in diabetic pregnancies: a devastating reality

There is an urgent need to understand the mechanisms underlying diabetes-induced congenital heart defects (CHDs) through basic science research and biomarker identification in human maternal circulation. Majority of the current research in CHDs is related to genetic analyses; however, environmental factors contribute to the majority of human CHDs, but the underlying mechanism is unknown. There is 60 million worldwide ...more »

Submitted by (@pyang0)

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

Details on the impact of addressing this CQ or CC :

More than 32,000 infants are born with heart defects each year in the United States, and about 1 in 150 adults are expected to have some form of congenital heart defect. Approximately, 25% of infants born with heart defects (2.4 per 1,000 live births) require invasive treatment in the first year of life, and in 2009 heart defects were the most common cause of infant death. Therefore, understanding the underlying causes of abnormal heart formation is an essential step towards developing effective new therapeutic treatments or preventions for heart defects. Using diabetes-induced CHDs as research models will reveal critical molecular pathways that contributes to heart cell proliferation and apoptosis.

Feasibility and challenges of addressing this CQ or CC :

The same types of heart defects seen in human diabetic pregnancies can be recapitulated in diabetic animal models, making rodents ideal models to investigate how maternal hyperglycemia may induce congenital heart defects. Dietary supplements of natural compounds may be effective against CHDs in diabetic pregnancies. Clinically, new imaging techniques needs be developed for the early diagnosis of CHDs in diabetic pregnancies. Biomarkers in human blood samples needs be detailed analyzed so that we can use small molecules such as microRNA for reliable and early diagnosis.

Name of idea submitter and other team members who worked on this idea : Peixin Yang

Voting

22 net votes
22 up votes
0 down votes
Active

Goal 1: Promote Human Health

Trans-kingdom regulation of HLBS systems

What is the interplay of the micro- and macroenvironment and their effect on gene and protein expression and overall effect on phenotypes in HLBS systems?

 

Need for unbiased approaches for information capture. Technologies for capturing real time, dynamic and contextual information

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

Increase and gain novel understanding of heart, lung, and blood physiologic systems

Feasibility and challenges of addressing this CQ or CC :

Emerging technologies, databases and merging of disciplines in the context of big data has the potential to make this feasible in the next 5-10 years

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

Voting

-6 net votes
3 up votes
9 down votes
Active

Goal 2: Reduce Human Disease

Heart Failure Therapies

We need much more support for critical basic research to understand and develop transformative therapies for this enormous health care burden. This is not simply a question of epidemiology and large multicenter population data bases. We really need hard core science. It is impossible to know where the next breakthrough will come, and setting aside funds for hot button things - stem cells, or iPS, or gene editing per ...more »

Submitted by (@dkass0)

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

Feasibility and challenges of addressing this CQ or CC :

NIH needs to stop trying to guess what the next big thing is and putting funds aside to support something that is popular at the moment. This has been done frankly with GWAS, with Stem cells, and perhaps ongoing now with "personalized medicine". All hot areas, but so are a ton of other things. IN my 30 years as a physician scientist, I cannot count on one hand the number of discoveries that were really transformative that came out of this type of ear-marked planning. Need more resources to support innovative individual scientists, particularly those with a track record of discovery, translation, and iinnovation We do not do that well enough at all.

Voting

6 net votes
18 up votes
12 down votes
Active

Goal 3: Advance Translational Research

Next Stage of COPD Discovery

1) Refinement of COPD subphenotypes for therapeutics, diagnostics and mechanistic interrogation. The NIH should encourage a strong focus on a) rigorous, mechanistically-reinforced definitions (chronic bronchitis, emphysema (with and without obstruction), frequent exacerbators, combined pulmonary fibrosis and emphysema) and 2) the development and optimization of animal model systems that replicate the different subphenotypes. ...more »

Submitted by (@lungmatbio1)

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

Details on the impact of addressing this CQ or CC :

If we could develop less costly and time consuming cell and animal models of COPD that reflect meaningful subphenotypes, we would be able to not only probe basic mechanism but also have reliable test platforms for candidate therapies.

There is typically a major obstacle between the acquisition of big data from observational disease cohorts, often broad but superficial, and the translation of these findings to basic discovery efforts. The clinical researchers speak a different language than the basic investigators and traversing this chasm with grant enticements might prove helpful.

Feasibility and challenges of addressing this CQ or CC :

This would require some suspension of the classic mechanistic, hypothesis driven proposals to develop these research tools.

There would need to be some reconstruction of study sections to permit these combined clinical-basic grants. The translational PPG was in keeping with this but should be reinforced with smaller grant programs such as RO1 level grants.

Name of idea submitter and other team members who worked on this idea : lungmatbio1

Voting

16 net votes
26 up votes
10 down votes
Active

Goal 1: Promote Human Health

Adult Cardiomyocytes in Culture

So much basic cardiovascular discovery relies on cell culture models. While cardiac cell lines exist (e.g. HL-1, H9c2), these often poorly model aspects of cardiomyocyte function in-situ (e.g. contractile function, metabolism). In contrast, primary cardiomyocytes isolated from adult animals (especially mice!) are not readily amenable to culture conditions. Even if cells can be kept alive, they are often refractory to ...more »

Submitted by (@paulbrookes)

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 challenge would provide tools for basic researchers to answer many key questions about basic cardiomyocyte function. Removing the "voodoo" element from these methodologies would be an enabling technology. In the neuron field, companies such as "brain bits" will ship tissue with specific protocols, to enable unskilled technicians to culture highly pure neuron subtypes in a matter of hours. Such methods have led to standardized methods in the field, which is good for reproducibility.

Feasibility and challenges of addressing this CQ or CC :

There have been several attempts at keeping adult myocytes alive in culture, using technologies such as electrical pacing, and inclusion of inhibitors in culture media. Likewise some AAV variants are known to transfect hearts in-vivo. However, no uniform widely-accepted methods are used between many different labs. Every lab has their own "trick" to get cells to behave. Many investigators can make a few cells on a dish survive, which is sufficient for single cell work (e.g. microscopy), but getting an entire culture of adult myocytes to survive beyond 24-48 hrs (the minimal time frame needed for genetic manipulations such as siRNA) would open up more common detection and assay measurements. Myocytes from larger animals (e.g. rabbits) are more stable and longer-lived in culture, but such methods do not appear to work for mouse CMs, which therefore precludes application of knockouts and other useful mouse resources.

Name of idea submitter and other team members who worked on this idea : Paul Brookes

Voting

-25 net votes
12 up votes
37 down votes
Active

Goal 2: Reduce Human Disease

Basic research

Are we funding enough basic research to support future research?

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

What is the nature of scientific knowledge? Are there enough opportunities for young scientists?

Feasibility and challenges of addressing this CQ or CC :

Funding of young scientists and of generalists is a challenge.

Name of idea submitter and other team members who worked on this idea : Rachel Braun

Voting

82 net votes
107 up votes
25 down votes
Active

Goal 4: Develop Workforce and Resources

Basic and Clinical Multi-disciplinary Partnerships to Understand Lung Disease

Basic scientists and clinicians have different training and bring different perspectives to lung disease research. Additionally, mechanisms that facilitate interactions of scientists from different fields may improve communication and facilitate novel ideas for lung disease research. I would like to see a funding mechanism that encouraged such partnerships in addressing fundamental disease questions and/or treatments. ...more »

Submitted by (@bmoore)

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

Details on the impact of addressing this CQ or CC :

This mechanisms could bring more perspectives to bear on questions in lung disease and would facilitate multi-disciplinary interactions and ideas.

Feasibility and challenges of addressing this CQ or CC :

If single awards, budgets would need to be large enough to allow for funding basic science as well as providing dollars to collect clinical samples. It should be possible to support some core facility infrastructure if needed and allow a budget that could account for basic scientists, animal work, study coordinators, clinicians, etc. Perhaps the RFA could require at least 3 different fields to be represented to try to facilitate multi-disciplinary approaches. Such a mechanism could help replace the loss of grants like SCOR grants and PPGs.

Name of idea submitter and other team members who worked on this idea : Beth Moore

Voting

3 net votes
11 up votes
8 down votes
Active

Goal 1: Promote Human Health

Transforming Transplantation with RISC

What is necessary to reprogram the immune system to improve transplant outcomes of hearts, lungs, and hematopoietic cells? While NIAID is a major funder of immunology research, we are a major contributor to stem cell research. Our resources could be combined, where NIAID would support this approach for autoimmune diseases, and we would support work in tolerance for transplants. If the NCI also wants to collaborate on ...more »

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

This innovative and transformative proposal could improve tolerance to many different types of transplants.

Feasibility and challenges of addressing this CQ or CC :

In 2002, Hochedlinger and Jaenisch (Nature 415:1035-1038) created a mouse by nuclear transplantation from a mature B-cell. This was proof of principle that the immune system can be reprogrammed entirely. Since then there has been little work in this area, but Reprogramming Immune System Cells (RISC) is risky but promising.

A second approach involves mechanisms that cancer cells use to evade immune detection. While most cancer research works to restore immune competence for therapy, the basic biology of evading immune detection could be exploited to improve tolerance. These approaches could be tested in an animal model in 5 years.

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

Voting

-3 net votes
15 up votes
18 down votes
Active

Goal 1: Promote Human Health

Hierarchical control of cardiac excitability

Imbalances in membrane excitability underlie a broad range of cardiac arrhythmias and conduction defects. Although we now know the genes encoding almost all ion channels, we have little understanding of how the macromolecular composition and relative numbers of different channel types is achieved to exert exquisite control over membrane potential changes in time. Even minor changes in this balance can lead to sudden ...more »

Submitted by (@garobert)

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

Details on the impact of addressing this CQ or CC :

The mechanisms involved reside at every conceivable level – genomic and epigenetic, transcriptional, translational and posttranslational. The tools required include structural biology, super resolution microscopy, single-molecule measurements, advanced molecular biology approaches, and bioinformatics and systems biology approaches. Fulfilling this unmet need will inform any system in which stoichiometry of macromolecular complexes critically determines normal function, and will therefore have a broad, transformative reach. The work will reveal novel mechanisms that will serve as targets for disease and therapeutic approaches.

Feasibility and challenges of addressing this CQ or CC :

Addressing this problem requires coordinated efforts by multidisciplinary investigators using diverse approaches as described above. Above all it requires a commitment of resources to basic science advances without which translation is impossible.

Name of idea submitter and other team members who worked on this idea : Gail Robertson

Voting

1 net vote
2 up votes
1 down votes
Active

Goal 1: Promote Human Health

Would unconditional basic income improve people's health & ease poverty better than conventional welfare programs?

Here's an article on the "Mincome" program which Canada tested in the 1970's in a small town: http://www.dominionpaper.ca/articles/4100 It had many positive effects on people's lives and health. Quotes: 'In the period that Mincome was administered, hospital visits dropped 8.5 per cent.' [...] '“When you walk around a hospital, it's pretty clear that a lot of the time what we're treating are the consequences of poverty,” ...more »

Submitted by (@apollia112)

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

Details on the impact of addressing this CQ or CC :

See comments

Feasibility and challenges of addressing this CQ or CC :

See comments

Name of idea submitter and other team members who worked on this idea : Apollia

Voting

0 net votes
2 up votes
2 down votes
Active