Goal 1: Promote Human Health

To expand knowledge of the molecular and physiological mechanisms governing the normal function of heart, lung, blood, and sleep systems as essential elements for sustaining human health.

Goal 1: Promote Human Health

Achieving Excellence in Health and Science Communication

At least two thirds of US adults use the internet to access health information. The accuracy and quality of health and science information found on news media websites, corporate websites of the healthcare industry, blogs of healthcare providers and social media networks varies widely. Nevertheless, this information can have a profound influence on the healthcare-related decision-making of patients. The anti-vaccination ...more »

Submitted by (@jalees)

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

Details on the impact of addressing this CQ or CC :

The NHLBI could lead the way by providing resources and funding to study the most effective ways to improve health and science communication. Examples of such approaches could be grants that fund how information pertaining to heart, lung and blood disease is disseminated to the public and how the quality of the content is regulated.

 

How do information hubs (media organizations, blogs, Twitter and Facebook accounts) assess the accuracy and quality of the medical and scientific content disseminated to their audiences?

 

Can collaborations between communicators (journalists, TED talkers, writers, etc.) and scientists/physicians help provide a more realistic and evidence-based portrayal of ongoing research efforts and the efficacy of treatments?

 

If the NHLBI is able to build such collaborations then the benefit to society could be quite significant. The public will be provided with resources to understand ongoing research efforts as well as obtain high-quality, up-to-date analyses of how research studies are relevant for them and their personal decisions regarding their health.

 

Even citizens who are not seeking medical advice would benefit from this because it would allow them to develop a realistic perspective and appropriate enthusiasm for the ongoing efforts in the basic sciences.

Feasibility and challenges of addressing this CQ or CC :

One challenge will be that this approach will require collaborations between diverse disciplines in order to be successful. Clinicians/Researchers in the cardiovascular, pulmonary and hematologic sciences will need to work closely with experts in communication sciences, behavioral experts and journalists to develop new approaches to health and science communication.

 

On the one hand, we want the science and medicine to be portrayed accurately, on the other hand, it is also important to ensure that this information is conveyed in a manner that is accessible for a non-specialist audience.

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

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Goal 1: Promote Human Health

Lung Anatomy and Environmental Exposure

How does human lung anatomical structure (e.g., angles of branch points, luminal diameter, etc.) affect exposure to environmental factors?

Submitted by (@nhlbiforumadministrator1)

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 : NHLBI Staff

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Goal 1: Promote Human Health

Rejuvenating Old Hearts and Lungs

Is there a true "mechanome" affecting normal heart function that could be studied to uncover important mechanically-stimulated pathways relevant to tissue development, maintenance, and repair in vivo? Are there mechanomics that predict and control fundamental biological processes linked to the body's natural healing and regeneration machinery? What if we could leverage 3D tissue engineering advances to rejuvenate aging ...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 :

Improvement of bioengineered heart and Lung tissues and organs may be accelerated by better understanding of mechanobiological processes. New therapeutic targets will emerge from identifying stress-regulated networks involved in the control of gene expression and cell phenotype.

Feasibility and challenges of addressing this CQ or CC :

Recent advances in atomic force microscopy and the development of optical tweezers has set the stage for advances in this area.

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

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43 up votes
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Goal 1: Promote Human Health

Computational biology modeling approaches

There is a need to develop computational biology modeling approaches to study normal variation in heart, lung, blood, and sleep (HLBS) systems.

Submitted by (@nhlbiforumadministrator)

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 : NHLBI Staff

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Goal 1: Promote Human Health

Epigenetics and Genomics

There is a need to target epigenetic mechanisms as new treatment options for hematologic disorders.

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

Details on the impact of addressing this CQ or CC :

Advances in the field of epigenetics and the understanding of various epigenetic mechanisms has provided a completely new ensemble of therapeutic targets for treating hematologic disorders – both non-malignant and malignant. These mechanisms have enormous implications for understanding the molecular underpinnings of the normal orderly development of hematologic disorders. Although one of the greatest challenges in effectively treating hematologic disorders is the diversity of molecular abnormalities that underlie a disease, there are a number of common threads emerging, including alterations in proteins that function through epigenetic mechanisms. Additional research focusing on epigenetic alterations and emerging targets is needed to identify the role of such proteins in the development of hematologic disorders in order to design potential targeted treatments to counter their effects. This research will further lay the groundwork for precision medicine, and will help to provide more insight on potentially critical determinants of responsiveness to therapeutic regimens.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology (ASH)

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Goal 1: Promote Human Health

Understanding Plasma Triglyceride Metabolism

Understanding basic mechanisms for intravascular triglyceride metabolism

Submitted by (@sgyoung)

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

Details on the impact of addressing this CQ or CC :

Over the past two years, it has become extremely clear that impaired processing of triglyceride-rich lipoproteins has an enormous impact on the frequency of coronary heart disease. For example, large genetic studies have shown that loss-of-function mutations in the gene for apolipoprotein CIII protect from atherosclerotic heart disease. Equally important is the observation that mutations in the gene for apolipoprotein AV are nearly as important as the LDL receptor as a cause of coronary heart disease.

 

The fact that plasma triglyceride metabolism is so important for atherosclerotic heart disease has caught the field by surprise. For many years, there was considerable doubt about the importance of plasma triglycerides for atherosclerotic heart disease. These doubts have vanished.

 

Now, in terms of basic research, the triglyceride metabolism field needs to play "catch up" ball. At this time, we have little understanding of intravascular lipolysis. We don't really know the molecular basis for the effects of apo-CIII, apo-CII, and apo-AV on intravascular lipolysis. The effects of these proteins on the LPL–GPIHBP1 complex are unknown. We don't understand how the lipid products of lipolysis move across capillary endothelial cells. We don't even understand why heparin releases LPL from GPIHBP1, and that observation is more than 60 years old! We don't understand the factors that explain differences in the efficiency of plasma triglyceride metabolism.

Feasibility and challenges of addressing this CQ or CC :

I believe that the field is now poised to understand intravascular lipolysis at the molecular level, and to investigate why some individuals have inefficient lipolysis and higher plasma triglyceride levels. Within the past few years, the "cast" of molecules that affect (or regulate) plasma triglyceride metabolism have come into focus. The field is poised for progress.

 

In part because of long-held doubts about the importance of plasma triglyceride metabolism, reagents for key proteins in intravascular metabolism are not in hand simply not in hand (recombinant proteins, specific antibodies). Developing and distributing these reagents is quite feasible, but it has not yet been accomplished.

 

Similarly, imaging tools are now available to understand the movement of the fatty acid products of lipolysis to myocytes and adipocytes, but there have been few attempts to use those tools.

 

We need to understand intravascular metabolism. At this time, no one understands the basics. No one knows how app-CII, app-CIII, and app-AV work. We need to understand how ANGPTL4 and ANGPTL3 regulate lipolysis. We need to understand the biochemistry of the LPL–GPIHBP1 complex. These tasks are feasible but will require hard work from many interested investigators.

 

In the end, once intravascular lipolysis is better understood, it is highly likely that there will be many new strategies for lowering plasma triglyceride levels and reducing the frequency of coronary heart disease.

Name of idea submitter and other team members who worked on this idea : Stephen G. Young

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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

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27 up votes
12 down votes
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Goal 1: Promote Human Health

Understanding normal aging

Understanding normal aging

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 :

While we are fully supportive of the recent emphasis on patient‐centered outcomes and implementation science, we are also reminded of the critical importance of investigating underlying mechanisms of pulmonary, critical care and sleep disorders. Recent discoveries have created exciting progress in the areas of cystic fibrosis, pulmonary hypertension, pulmonary fibrosis, and biological therapies in asthma. Only through further efforts to elucidate underlying mechanisms are new therapeutic approaches likely to emerge. Promoting further academic‐industry interactions are likely to yield benefits, which will ultimately lead to improvements in the health of our nation.

Name of idea submitter and other team members who worked on this idea : Research Advocacy Committee, American Thoracic Society

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Goal 1: Promote Human Health

Extreme makeover: harnessing adaptation mechanisms for therapy

What extreme adaptive physiological mechanisms in heart, lung, and blood systems might have the greatest potential to be targeted or employed in therapeutic strategies? Human physiology, including the heart, lung and blood systems, is known to possess extreme adaptive mechanisms to counter extreme conditions or unusual situations. Although some studies are being done, many of these mechanisms have not been fully explored ...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 :

May lead to new therapeutic strategies for HLB diseases. May improve our understanding of HLB physiology and adaptation.

Feasibility and challenges of addressing this CQ or CC :

It is feasible to ask specific questions about adaptation mechanisms under extreme conditions and develop experiments to test them. This can be done in various experimental models as well as in humans.

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

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Goal 1: Promote Human Health

Circadian-coupled rhythms in lung health

Does the homeostasis and health of the lung depend on circadian-coupled genomic function?

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 :

The circadian genome is a highly conserved system producing 24-hr rhythms in gene expression in the lung. Uncovering the molecular/cellular pathways under circadian control and their significance would provide a new generation of mechanistic understanding of lung health and development.

Feasibility and challenges of addressing this CQ or CC :

Delineating circadian mechanisms of lung function would enable new strategies to phenotype, diagnose, and mange lung disease to be developed and tested.

Over the past decade, new discovery has uncovered a mechanistic interface between the circadian clock and fundamental cellular processes including oxidative stress, cell metabolism, immune and inflammatory responses, epigenetic modification, hypoxia/hyperoxia response pathways, endoplasmic reticular stress, autophagy, and regulation of the stem cell environment. While each of these processes is involved in lung function, the significance of circadian regulation in the development and maintenance of lung health is not well-understood.

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

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Goal 1: Promote Human Health

Evaluation of large-scale regulatory efforts in the US and elsewhere

A number of cities(e.g Berkeley), states and countries (e.g Mexico's SSB tax, Chiles SSB and soon marketing controls and food package front of package label) will go into effect. Rigorous evaluations of the efforts will provide some sense of their potential to effect food purchase and dietary pattern and ultimately cardiometaboiic changes. Serious rigorous independent evaluations are needed to learn if these options--pushed ...more »

Submitted by (@popkin)

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

Details on the impact of addressing this CQ or CC :

We must learn what we can from the natural experiments not only in the US but globally about both the effects of these efforts on food industry behavior as well as household and individual food purchases and dietary patterns and subsequently their effects on obesity and key cardiometabolic outcomes. This requires serious rigorous teams of scholars to utilize a combination of commercial data sets on food purchases, individual diet, body composition measures of obesity and fat composition and biomarkers.

Feasibility and challenges of addressing this CQ or CC :

These efforts are occurring and will be accelerating across many countries in Asia and Latin America. At the same time many cities or states in the US are moving to implement limited sets of key changes. There is a pressing need to learn if these efforts truly will matter and what changes would be needed to enhance their impact, if any. Finding large-scale regulatory ways to reduce improve our diets, prevent/reduce the prevalence of obesity and all the diet and obesity-related NCD's is critical.

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

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42 up votes
20 down votes
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Goal 1: Promote Human Health

Medical marijuana and COPD

Medical marijuana and COPD

Submitted by (@elizabethkberger91)

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

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12 up votes
31 down votes
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