Goal 3: Advance Translational Research

To facilitate innovation and accelerate research translation, knowledge dissemination, and implementation science that enhances public health.

Goal 3: Advance Translational Research

Calcium channels in cardiovascular functions and diseases

Fifty years ago Prof. Harald Reuter of the University of Bern, Switzerland obtained the first experimentally supported evidence that the calcium channel is a physiologically distinct entity. Further stimulated by the synthesis of the dihydropyridine calcium channel blocker nifedipine, the field of calcium channel research rapidly encompassed cardiovascular and other powerful biomedical directions.

Submitted by (@soldatovn.humgenex)

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 coming Theme Issue of Current Molecular Pharmacology "50th Anniversary of Calcium Channel Research: Biomedical Perspectives" brings together leading experts in calcium channel research with the aim of discussing new ideas and recent developments in research of voltage gated calcium channels and calcium signaling with specific focus on biomedical perspectives. This CMP Theme issue may be particularly interesting for those who are involved in molecular cardiovascular research. Please see further: http://benthamscience.com/journal/upcoming-articles.php?journalID=cmp

Feasibility and challenges of addressing this CQ or CC :

In 2010, heart diseases cost the United States $316.4 billion in health care services, medications, and lost productivity (Circulation 2010, 121, e1). Search for new therapeutical targets associated with the family of calcium channels becomes an increasingly powerful future direction.

Name of idea submitter and other team members who worked on this idea : Nikolai M. Soldatov, Ph.D., Guest Editor, and authors of 23 papers of the CMP Theme Issue

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Goal 3: Advance Translational Research

Diagnosing Risks to Sleep Health and Therapeutic Responses

What are practical point-of-care diagnostic biomarkers that could be used for assessment of sleep/circadian health, sleep disorders, and the risk of sleep-related heart, lung, and blood diseases?

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 :

Existing assessments based on intensive overnight physiological measurements of sleep interpreted by medical specialists are impractical for the goal of diagnosing a spectrum of sleep-related health risks and the need to protect the safety of the public at large. Sleep/circadian-related biomarker panels are needed to enable the development of practical diagnostic tests for point of care implementation, and determining whether the response to therapy has been successful.

Feasibility and challenges of addressing this CQ or CC :

Mature high-throughput genomic technologies combined with recent advances in our knowledge of sleep-coupled pathways provide a rich foundation for systematic investigation and the application of computational modeling strategies.

Discovery research advances implicate an array of cellular sleep and circadian mechanisms in pathophysiological pathways leading to cardiometabolic and pulmonary disease. Irregular and disturbed sleep impairs cellular biological rhythm in all tissues and organs leading to oxidative stress, unfolded protein responses, and impaired cell function. These pathophysiological changes are accessible to existing high-throughput quantitative technologies facilitating systematic study and the identification of candidates and panels of candidate correlating with sleep health status.

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

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Goal 3: Advance Translational Research

Greating grant mechanism for fostering collaboration with industrial partners

There is a disconnect between the cardiovascular devices industry and the basic research that is conducted in the field by biomedical engineering researchers. Technological solutions that the industry is converging to are not well informed by the advances in basic translational research. A distinct funding mechanism should be created for fostering such collaborations. To motivate for profit cardiovascular device manufacturers ...more »

Submitted by (@danny.bluestein)

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 : Danny Bluestein, Ph.D.

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Goal 3: Advance Translational Research

The use of administrative and billing data in COPD care quality improvement

What is the validity of administrative/billing data to evaluate the quality of COPD care as part of quality improvement initiatives? What care practices can be assessed using these data?

Submitted by (@ngrude)

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 : Nina Bracken, COPD Foundation advocate

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Goal 3: Advance Translational Research

Next generation of cellular blood products for clinical use

What advancements in our understanding of hematopoietic stem cell differentiation can be combined with practical developments in novel processing and storage technologies to develop the next generation of transfused blood therapeutics? There is a dearth of tools to evaluate the efficacy of transfused blood products, although this is the most commonly employed therapeutic procedure in the US. There is also no financial ...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 :

The management of blood transfusions in the clinical setting is undergoing drastic changes in the US with the realization that “more” is not better and that transfusion of red blood cells while life-saving in hemorrhagic settings may be associated with increased morbidity and mortality in more stable patients. Questions have also been raised as to the benefit of prophylactic (most transfusions) versus therapeutic platelet transfusions. Additionally, while red blood cells are being transfused to bring oxygen to tissues in need, and platelets are transfused to prevent/reduce further bleeding, their effectiveness in doing so is not known since often not measurable- hemoglobin levels or platelet corrected count increments are non-sensitive and inadequate effectiveness surrogates. Personalized blood cellular products derived from hematopoietic precursors or resulting from the implementation of novel processing and storage technologies could result in next generation cellular therapeutics that could potentially be used in smaller quantities; deliver specific therapeutics where needed; be effective (e.g., oxygenate hypoxemic tissues); be pathogen-free, less immunogenic, and free of potentially harmful plasticizers; and be available especially in times of emergencies.

Feasibility and challenges of addressing this CQ or CC :

Progress has been made in the last decade in producing blood products from stem cells, including gene-engineered cells. It is now possible to produce red blood cells and platelets from stem cells although the efficiency is low and the safety and efficacy of such products need assessment. New processing (e.g., pathogen-reduction) and storage (e.g. cold storage for platelets, new storage plastic bags) technologies are being considered although progress has been hampered by a lack of financial incentives and regulatory hurdles.

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Goal 3: Advance Translational Research

Natural Experiments and Obesity

How can approaches, such as natural experiments, be used to capture the evolution and impact of policies/environmental change that are related to obesity? There needs to be a mechanism that can quickly support the funding of natural experiment research. For instance, NIDDK and NICHD participate in a rapid response PAR that funds natural experiments in a timely manner. It only takes about 4 months from when the application ...more »

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

Gaining a better understanding of the impact of natural experiments on obesity would help us better understand how best to translate findings into public health action.

Feasibility and challenges of addressing this CQ or CC :

It is feasible to address the impact of natural experiments and obesity because there are currently naturally experiments taking place and we should capitalize on it.

There are a growing number of policies (e.g., caloric labeling) and environmental changes (e.g., bicycle lanes), being implemented to address obesity. These policy and environmental changes can be seen as natural experiments and should be evaluated. While there are challenges to revaluating real-world implementation of polices/environmental changes, there is the opportunity to increase external validity.

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

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Goal 3: Advance Translational Research

Addressing Health Care Disparities Requires Pragmatic Research

Jumpstarting progress in eliminating health care disparities requires comparative effectiveness and implementation research (T3 and T4) regarding optimal strategies for ensuring health care equity in the real world. Ensuring minority and other socially disadvantaged groups receive and benefit from evidence-based interventions at the same rate as others requires pragmatic research that identifies and addresses barriers ...more »

Submitted by (@kevinfiscella)

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

Details on the impact of addressing this CQ or CC :

Meeting this challenge offers promise for elimination of disparities in morbidity and mortality among minority and other socially disadvantaged groups. Many major health care organizations are hungry for science-based interventions and implementation strategies for ensuring equitable care relevant to heart, lung, blood and sleep conditions. Pragmatic scientific evidence in these areas is urgently needed.

Feasibility and challenges of addressing this CQ or CC :

There are several feasibility challenges. The first is the broader challenge surrounding pragmatic, comparative effectiveness and implementation research including its integration within health care systems. Too little of this type research is conducted by funded institutions within their own health care systems. This failure reduces the likelihood that research findings, including best strategies for improving equity in health care delivery, will be adopted by health care systems. Ultimately, those responsible for implementation along with those receiving care must be active research partners in conducting pragmatic research in order to ensure that the research addresses real world priorities and feasibility issues.This represents a major shift in research paradigms but is critical to the success of health care disparities research.

 

The second challenge is that research funding streams narrow along the translational continuum. This poses a challenge to pragmatic research that focuses on equity in care. There is no doubt that research along the entire research continuum is needed to address health and health care disparities. However, research focusing on ensuring provision of evidenced-based interventions for groups least likely to receive them will have the most immediate impact.

Name of idea submitter and other team members who worked on this idea : Kevin Fiscella, MD, MPH

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Goal 3: Advance Translational Research

Regenerative Medicine 2.0 in Heart and Lung Research - Back to the Drawing Board

Stem cell therapies have been quite successful in hematologic disease but the outcomes of clinical studies using stem cells for cardiopulmonary disease have been rather modest. Explanations for this discrepancy such as the fact that our blood has a high rate of physiologic, endogenous turnover and regeneration whereas these processes occur at far lower rates in the heart and lung. Furthermore, hematopoietic stem cells ...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 :

Some barriers to successfully implementing cardiopulmonary regeneration include the complex heterogeneous nature of the heart and lung.

 

Hematopoietic stem cells can give rise to all hematopoietic cells but the heart and lung appear to contain numerous pools of distinct regenerative stem and progenitor cells, many of which only regenerate a limited cell type in the respective organ. The approach of injecting one stem cell type that worked so well for hematopoietic stem cells is unlikely to work in the heart and lung.

 

We therefore need new approaches which combine multiple regenerative cell types and pathways in order to successfully repair and regenerate heart and lung tissues. These cell types will likely also require specific matrix cues since there are numerous, heterogeneous microenvironments in the heart and lung.

 

If we rethink our current approaches to regenerating the heart and lung and we use combined approaches in which multiple cell types and microevironments are concomitantly regenerated (ideally by large scale collaborations between laboratories), we are much more likely to achieve success.

 

This will represent a departure from the often practiced "Hey, let us inject our favorite cell" approach that worked so well in hematologic disease but these novel, combined approaches targeting multiple endogenous and/or exogenous regenerative cells could fundamentally change our ability to treat heart and lung disease.

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

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Goal 3: Advance Translational Research

Novel Technologies & Clinical Therapeutics

How can NHLBI harness the power of novel technologies involving nucleic acid delivery and gene editing for clinical therapeutics?

Submitted by (@skrenrich)

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

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Goal 3: Advance Translational Research

Recognizing that HLB are components of a whole person

RASopathies is one of a group of syndromes that include heart, lung and blood issues, but these are not all the concerns. Recognizing that these organs are part of a functional network (called the human body), partnering with other Institutes could help expedite knowledge of these systems. Leveraging small pockets of funds through mechanisms such as R13 grants where the primary institution is not NHLBI is an inexpensive ...more »

Submitted by (@lschoyer)

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

Feasibility and challenges of addressing this CQ or CC :

Not hard, no cost.

Name of idea submitter and other team members who worked on this idea : Lisa Schoyer, President, RASopathies Network USA

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Goal 3: Advance Translational Research

Healthcare Inequity

Many continue to pay higher benefits for less care. Often they are seniors who do not need OB/Gyn or pediatric benefits, etc. They are not covered for eyeglasses, dental work, etc. Those covered under Obama care plans and subsidies are entitled to more care. Now states are legalizing recreational drug use, same sex marriage, etc. Why? It is only logical to realize this will place more unnecessary burden on the already ...more »

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 : Suzanne Michalek

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