Goal 4: Develop Workforce and Resources

Establishment of an independent study section on Pulmonary Vascular Biology and Translational Research

The research on pulmonary vascular biology including smooth muscle cell biology and endothelial cell biology and related pulmonary vascular diseases such as pulmonary hypertension and related right heart failure, and endothelial dysfunction in lung vascular inflammation and acute lung injury, as well as pulmonary embolism and lung transplantation has been rapidly expanding. The field is attracting an ever increasing ...more »

Submitted by (@yyzhao)

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

Details on the impact of addressing this CQ or CC :

Establishment of a study section on Pulmonary Vascular Biology and Translational Research will provide adequate funding to stimulate innovative research on this rapidly expanding field and promote translational research and thereby promote human health by providing potential novel therapeutic strategies for the devastating diseases such as pulmonary hypertension and acute lung injury.

Name of idea submitter and other team members who worked on this idea : Youyang Zhao, Kurt Denmark, Asrar B. Malik, Mark Gladwin, Jahar Bhattacharya, Michael Matthay, Sharon Rounds, Jason Yuan

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23 net votes
50 up votes
27 down votes
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Goal 4: Develop Workforce and Resources

Training approaches in lymphatic biology

The lymphatic vascular network connects the parenchymal interstitium through the nodes to the veins. Lymph serves as the transport pathway between these compartments and via its flow, controls interstitial fluid, macromolecular exchange, lipid absorption, immune cell trafficking and is critical to edema prevention/resolution, lipid metabolism, inflammation and immunity. Knowledge of this vascular network lags far behind ...more »

Submitted by (@dcz000)

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

Details on the impact of addressing this CQ or CC :

NIH has acknowledged that the lack of training in the field of lymphatic biology has impaired research progress in the area. Traditional methods that the NIH uses (T32) have not adequately addressed this issue as there are currently NO such programs in existence. One of the critical problems that must be overcome to advance the field is that few individual institutions in the US have a large enough body of lymphatic biology investigators to fit the classic training grant schemes. Overcoming this hurdle will significantly help advance research in the field. Consideration of other innovative approaches that utilize web-based or other methods to deliver distance education among local or regional institutions in this field should be investigated. Establishment of these innovative approaches would broaden the pool of investigators for research training and would significantly advance the field and thus be of high impact.

Feasibility and challenges of addressing this CQ or CC :

Research in the lymphatic biology field has historically lagged behind other vascular areas. However, interest in lymphatic biology and medicine has grown rapidly over the last decade. The Lymphatic Education & Research Network (formerly LRF) has had a long-standing commitment to developing research and training in lymphatic biology through its post-doctoral fellowship program, support for conferences/symposia and by providing travel funds for early-stage investigators to attend these meetings. Since very few places in the US have enough researchers trained and active in lymphatic biology, initiatives to broaden the base for research training would have to utilize novel approaches. Thus, the challenge will be to develop training programs that can address the needs of new lymphatic biologists at multiple institutions at geographically distributed sites. Approaches that use modern communication IT technology, and distance learning methods could deliver parts of the training. But innovative approaches to incorporate training beyond didactic learning need to be developed.

Name of idea submitter and other team members who worked on this idea : D. Zawieja

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12 net votes
13 up votes
1 down votes
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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 »

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

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5 net votes
23 up votes
18 down votes
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Goal 1: Promote Human Health

Intersecting Developmental Biology with Vascular Physiology and Biology

Although many think of the vasculature as a lump sum of vessels that all react in a similar fashion to a certain stimulus, e.g., alpha-adrenergic activation, this is not the situation. For example, coronary resistance vessels show little to no direct response to alpha-adrenergic activation while resistance vessels in most organs show marked constriction. Another example is the response of different vessels to angioplasty ...more »

Submitted by (@wchilian)

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

Details on the impact of addressing this CQ or CC :

A challenge facing many specialists in vascular medicine, vascular surgery, and cardiology is understanding the ramifications, and the basis, of the vascular pathology in the context of the organ system. Another way of re-stating this as a question is: Are the unique attributes of the vascular biology, pathology and physiology of a particular organ system connected to specific aspects of development. This question would help both the basic on clinical scientists understand the basis of why a blood vessel in the kidney may be different than one in the heart, or in the brain with the goal of devising more selective therapies to approach vascular disease in specific organs. Scientists in the area of vascular development have long appreciated that vascular cells in different organs arise from different embryological origins; yet how this information translates into the intricacies of vascular control, or responses to pathology is not resolved. Understanding the basic biological mechanisms of how the embryological source of the vasculature affects pathology and physiology could engender treatment of vascular disorders.

Feasibility and challenges of addressing this CQ or CC :

This idea could be implemented by encouraging multi-PI efforts from vascular developmental biologists, and investigators engaged in studies of microvascular control mechanisms and/or vascular biologists interested in vascular pathologies such as restenosis and vascular lesions. Advances in fate mapping techniques have enabled developmental biologists to track embryological origins of cells into specific organ systems into adulthood. With such a multi-faceted approach a better understanding of vascular physiology and pathophysiology will be obtained that hopefully will be translated into more effective treatments.

Name of idea submitter and other team members who worked on this idea : William M. Chilian

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15 net votes
26 up votes
11 down votes
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Goal 1: Promote Human Health

Human normal variation and resilience across lifespan

What is the measureable normal human variation at the -omic, cellular, organ, and system levels within the population and across the lifespan? • What are the range of normal human cellular functions that create resilience at all levels—cells, organs, organ systems? • What inter-organ, tissue, and cellular communications maintain individual health and the health of populations? • How do we understand why individuals with ...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 :

• Will provide a better definition of what is normal in order to better interpret and exploit the big data available through increased personalized monitoring and use of EMRs.

• Insights into the underlying mechanisms of resilient phenotypes will provide new paradigms for disease prevention and treatment.

Feasibility and challenges of addressing this CQ or CC :

Feasibility will depend on the level of investment (large) and accessibility to commons data.

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

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19 net votes
26 up votes
7 down votes
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Goal 1: Promote Human Health

Host and environmental factors effect on transplantation biology and regenerative medicine

How does inflammation and cell injury induce the immune system during transplant rejection? How do we control immune responses to enable cell- and tissue-regenerative strategies? • How does inflammation and cell injury induce the immune system during transplant rejection? • How do we control immune responses to enable cell and tissue regenerative strategies? • How do we use iPS cell based and gene editing based therapies ...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 :

Treatment of human diseases

Feasibility and challenges of addressing this CQ or CC :

Facilitated by progress in genome editing, stem cell biology, immunology

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

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34 net votes
48 up votes
14 down votes
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Goal 3: Advance Translational Research

Human Heart Systems Biology

In the human failing heart, it is the systems biology that ultimately fails: electrical, mechanical, and chemical perturbations in their function do not manifest in isolation, but critically impact on each other in health and disease. Investigation of human myocardium, unlike inbred rodent models, is challenging since no two humans are identical. There is a need for the collection and assessment of clinical patient data, ...more »

Submitted by (@janssen.10)

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

Details on the impact of addressing this CQ or CC :

Procured/stored tissue from these hearts could be made available NHLBI/NIH-wide, and studied by a large number of investigators on protein levels, RNA/DNA level, and/or histological assessments. This data could then be correlated to any other parameter assessed on these hearts, providing correlative guidance, through systems biology/neural network programming, for future mechanistic studies. For each additional parameter investigated, the number of correlation analysis (with any and all parameters, including clinical and biometric parameters) would mathematically double.

Feasibility and challenges of addressing this CQ or CC :

Supporting the basic collection of these in vivo and in vitro parameters and possibly the logistics for tissue distribution to collect correlative mechanical, proteomics, genomics, and histology data for correlation with the in vivo and in vitro data would allow for an NIH/NHLBI-wide translational approach to human heart failure that could encompass everyone’s “favorite” molecule, protein, pathway, and disease etiology. A logistical challenge is that such a project would likely exceed the funding of a single standard grant, but more importantly would surely exceed the standard 4-5 year duration, requiring long-term vision, planning, and buy in from NIH/NHBLI and investigators.

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

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6 net votes
13 up votes
7 down votes
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Goal 1: Promote Human Health

A Systems Approach - Human Cardiac Electromechanical Activity

The challenge is to identify limitations in using data from non-human animal species for elucidation of human electromechanical function/activity and to identify what specific information and computational approaches need to be incorporated. To aid in achieving such a goal, it might be useful to convene a series of workshops to build consensus and improve communication among investigators working at the same horizontal ...more »

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 :

This will provide an in silico computational platform to study human cardiac pathology. Note: by different horizontal levels, we mean for example measuring and modeling individual ion channels, transporters or myofilament properties in myocytes. By different vertical levels, we mean for example gogenomic/proteomic to cellular, and cellular to more integrative levels.

Feasibility and challenges of addressing this CQ or CC :

Advances in high-speed computation techniques and high-throughput measurement make the achievement of this challenge doable.

An integrated understanding of the eletromechanical activity of the human heart is needed to develop more effective approaches to cardiac disease diagnosis, treatment, and prevention. Robust computational models of human electromechanical activity that incorporate ion channel kinetics, calcium handling and dynamic changes in the intra-/extracellular milieu from human cardiac tissues are needed develop such an understanding and to provide an experimental platform to test interventions designed to maintain cardiac function. Computational models should be scalable and incorporate subcellular molecular mechanisms to whole system levels of integration to be most effective.

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

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7 net votes
20 up votes
13 down votes
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Goal 2: Reduce Human Disease

Redox regulation of cardiovascular and lung disease through thiols

Redox imbalance as represented by alterations in oxidative versus reductive stresses are well appreciated to occur during nearly all forms of cardiovascular and lung diseases. However, specific molecular mechanisms responsible for these changes remain largely unknown and poorly organized. Study of redox biology principals has revealed that protein cysteine thiols are a unique target for redox posttranslational modifications ...more »

Submitted by (@ckevil)

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

Details on the impact of addressing this CQ or CC :

Protein cysteine thiols are recognized to be important for multiple signaling and cell biology functions due to unique properties of oxidation/reduction resulting in a 'thiol switch'. However, oxidative modifications of thiols are highly complex involving nitrosation, sulfhydration, sulfenylation, and glutathiolyation among many others. It has become increasingly clear that these posttranslational modifications are associated with cardiovascular and pulmonary pathophysiology. Yet, many important questions remain such as: how these thiol modifications occur during disease and differ from health? How do these thiol switches impact protein function involved in cellular pathophysiology? And can thiol switch manipulation be exploited for therapeutic purposes to maintain cellular and organ health or treat disease? In order to begin to answer these questions, careful and comprehensive investigations are required to understand thiol-switching principals employing a host of molecular, biochemical and pathophysiological approaches.

Feasibility and challenges of addressing this CQ or CC :

Given the significant advances in quantitative analytical chemical and molecular techniques, molecular redox mediators and pathways, non-invasive imagine modalities and comprehensive translational study designs; multiple fields are uniquely poised that could provide significant insight into this critical challenge. Primary objectives would be to establish consensus analytical methodologies, chemical and molecular biology approaches, and cellular and animal models in conjunction with rigorous clinical investigations. Results from efforts at understanding the importance of ‘thiol switches’ will make significant clinical impact on cardiovascular and lung pathogenesis and would feasibly be accomplished in 5-10 years.

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-5 net votes
5 up votes
10 down votes
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Goal 1: Promote Human Health

Cardiac Engineering – Deciphering the Cardiome

To maintain cardiac health and prevent disease, there is a need to decipher the cardiome of cells and genes and use this knowledge (1) to better understand cardiac structure and function and (2) to engineer systems on the level of organs, organ systems, and the entire individual.

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 :

Improved CV health

Feasibility and challenges of addressing this CQ or CC :

new advances in study of the cardiome

Advances in in the sub-micro-world over the past several years have led to greater opportunities to better understand cells and genes. These new developments have and will continue to provide greater insight into understanding cardiac structure and function, which has and will likely to result in improved therapies for heart disease. The advances being made in science and technology have expanded the frontiers of cardiology as a result of important advances in micro-imagining and molecular diagnostic methods. These advances have transformed classical study of the macro-world of living human beings and the cardiac disease that afflict them.

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

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-16 net votes
10 up votes
26 down votes
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