Goal 1: Promote Human Health

Environmental stimuli and the lung: predictors of homeostatic or pathological responses

What are the molecular and cellular responses in the lung that occur after environmental stimuli that predict homeostatic resilience or transition to disease, disorder, or aging?

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

Details on the impact of addressing this CQ or CC

Addressing this line of research could define biomarkers and pathways useful for prediction of how human response to an external stimulus of varied nature (i.e. microorganism, chemical, physical) could lead to specific outcomes in relationship to the duration of the exposure and the genetic makeup of the individual exposed. Identification of early signals and the pathways involved could lead to novel preventative or therapeutic approaches.

Feasibility and challenges of addressing this CQ or CC

Methods for systems biology approaches to address complex pathobiological iterations are ready to be exploited to answer these questions.
Great progress has been made in the clarification of basic mechanisms of molecular and cellular response to environmental stimuli, in cross-sectional analyses. The continuum of the response in relationship to the genetic background of individuals responding with a homeostatic or pathological long-term outcome is missing from these data.

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

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Goal 1: Promote Human Health

Brain-Heart Connections

Depression and CHD will become the 2 leading causes of disability in the next decade. Chronic as well as traumatic stress increases CVD risk by about 50%. Although we understand that there are connections between psychosocial stress, affective disorders, and CVD, we do not understand the vast array of brain areas that impact the CV system and the mechanisms connecting them. Neuroscience has made great leaps in understanding... 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

For example, we still do not have a comprehensive understanding of how depression increases incident CHD.

Alternative treatments for depression are needed that target disrupted pathways known to promote CVD (e.g. autonomic, inflammation).

What are the mechanisms through which PTSD doubles incident CHD within a decade?

What are the mechanisms through which exercise, sleep, and certain diet patterns mediate the effects of psychosocial stress on health?

Not all stressed people get CVD and some data suggests that coping style mediates stress effects on CVD risk. If so, perhaps we can teach coping styles. But to do so we need to know more about whether and how certain coping styles modulate stress effects on the CV system.

A major cause of psychosocial stress in modern America is social density. The higher the density, the less tolerance there is for deviance from the norm. How does increased social density effect CV physiology? Are there ways to intervene through spatial partitioning or interaction patterns that alter perceptions of crowdedness or lack of privacy?

Feasibility and challenges of addressing this CQ or CC

We have all the tools to address this over-arching area and these specific questions. They just need to be made a priority.

Name of idea submitter and other team members who worked on this idea Carol Shively

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Goal 1: Promote Human Health

Mapping the Vasculome

What is the best method to develop an integrated map of the expression patterns of the vasculature (RNA, protein, and epigenome) within each organ system?

 

Sampling standards and quality control are major outstanding issues.

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 vasculome is comprised of a vast network of vessels that globally interacts with all of the other organ systems within the body. Disorders of the vasculature have a significant adverse effect on those organ systems and are a major source of mortality and morbidity. Systematic mapping of vasculome expression will reveal disease causality patterns that have thus far been unobserved.

Feasibility and challenges of addressing this CQ or CC

The tools are available, the coordination is not. The NHLBI and VBHB have the expertise, the experience, and the leadership necessary to oversee the multiple studies, date collections, and organizational systems needed for mapping the vasculome.

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

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Goal 1: Promote Human Health

Continuous blood pressure and outcomes monitoring

Currently technology exists for continuous, non-invasive, insertable (not breaking any skin), blood pressure monitoring. At the same time micro-vascular health and whole body inflammatory response can be monitored continuously. The challenge is for the integration of these technologies into a simple device so we can begin to produce long term data on genetic and environmental influences on outcomes.

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

Details on the impact of addressing this CQ or CC

Blood pressure monitoring via a pressure cuff has been shown to miss many of the problems with elevated blood pressure (e.g. morning surge, normotensive salt sensitivity). Continuous monitoring of blood pressure while measuring micro-capillary health will enable feedback control of the inflammatory events surrounding hypertension, salt sensitivity and related diseases.

Feasibility and challenges of addressing this CQ or CC

At least three companies are producing research grade products for wearable continuous blood pressure monitoring. The Qualcomm X Prize has yielded several technologies that could continuously monitor microvascular health (e.g. inflammation). We have developed a genetically driven decision tree that will enable physicians can classify their patients into one of 6 cardiovascular types. Each type has a personalized therapy, many of which rely on dietary instead of pharmaceutical treatment. Thus, we need to move cardiovascular diagnosis and therapies into the modern wellness age of medicine.

Name of idea submitter and other team members who worked on this idea Robin A Felder

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Goal 1: Promote Human Health

Emerging importance of RNA regulation

What are the roles of RNAs (e.g., microRNAs, long non-coding RNAs, etc.) in myocardial growth, adaptation, and injury healing response?

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

Details on the impact of addressing this CQ or CC

As an example, recent studies suggest key regulatory roles of RNAs (e.g., microRNAs and long non-coding RNAs) in cardiac pathological hypertrophy and heart failure. Better understanding of such mechanisms will spur development of new therapies based on these mechanisms.

Feasibility and challenges of addressing this CQ or CC

Most of the infrastructure and methods are in place. There appears to be growing interest and excitement about the potential of this research area. However, this field needs more researchers.

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

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Goal 1: Promote Human Health

Establishment of a permanent exercise study section

Funding opportunities explicitly for studies of exercise have not been a major NIH priority. The NHLBI has been an exception to this, but the non-existence of a true exercise study section still makes funding a challenge for individuals in the field of Exercise Science. Exercise, along with sleep and diet, is one of the pillars of health and has been shown to be highly beneficial for a number of medical conditions. However,... 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 MattS

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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

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

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Goal 1: Promote Human Health

Do our modern "traditional" sleep schedules defy nature?

Here's an interesting article which shows that the modern tradition of eight hours of unbroken sleep might actually be unnatural, and quite different from what our ancestors typically did:

http://www.bbc.com/news/magazine-16964783

So, maybe the majority of our modern societies (even the people without recognized sleep disorders) are unwisely fighting against biology?

Perhaps a lot of people's health issues, such as... 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

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

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Goal 1: Promote Human Health

Endoglin Regulates biolgy and signal transduction in vascular smooth muscle cells

Why loss of endoglin causes HHT is not known. Endoglin is expressed by vascular smooth muscle cells and endothelial cells.

What is the role of endogin on vascular smooth muscle cells and why its loss contributes to HHT and other vascular malformations

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

Details on the impact of addressing this CQ or CC

Vascular smooth muscle cells wrap around arteries and control their diameter.

Name of idea submitter and other team members who worked on this idea Marianne Clancy MPA, Chris Hughes PhD

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Goal 1: Promote Human Health

Holistic Approach to Evaluating Aging Congenital Heart Cohort

There are not enough large data sets available for researchers to study young and aging patients with congenital heart disease (CHD). There is a need to develop a low cost, high impact, large data collection initiative.

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

Details on the impact of addressing this CQ or CC

Funding an initiative would challenge the community to explore the issues related to the aging CHD community and the combination of physical and emotional stresses. Once the data are available, it may open new areas of targeted healthcare and medicine.

Feasibility and challenges of addressing this CQ or CC

This community continues to grow, age, and we could only hope they continue to enjoy good health and improved function in our society.
So often RO1's and other grant mechanisms have a singular disease focus approach to a cohort, but this growing and aging population is influenced by more than one concern. Medically, there are common chronic conditions like cardiovascular disease and obesity (with all their concomitant issues), and newer issues such as family and child bearing, quality of life related to employment, social inclusion/exclusion, and the aging of the caretakers.

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

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Goal 1: Promote Human Health

Venous Thromboembolism

How can individual VTE risk-assessment scoring be combined with promising biomarker candidates in order to help predict risk in the general patient population and prevent unprovoked low-risk VTE cases?

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 VTE field is approaching a new era of therapy in which predictive measures at the primary care level will identify those patients most at risk for VTE. With the identification of predictive biomarkers for VTE occurrence, efforts will be necessary to develop point-of-care or in-home biomarker testing devices to improve risk-assessment scoring and identification, so that patients could then be treated before progression. It will also be critical to accelerate risk-scoring systems that are beginning to incorporate biomarker candidates into the algorithm for use in clinical trials. Studies that will focus on correlating risk-assessment scores and biomarker research findings will provide a more accurate risk prediction and diagnostic value.

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

Origins of early disease

Defining the origins of early disease.

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

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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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