Goal 3: Advance Translational Research

Advancing the preservation of cellular therapies

Cell therapies are produced in specialized facilities and the viability/function of the cells must be retained in order to permit transportation to the site of use, coordination with patient care, etc. Current options for preserving cells are limited. Conventional methods of cryopreservation may result in poor post thaw function and are difficult to use at the point of care. Liquid storage of cells is typically limited ...more »

Submitted by (@hubel001)

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

Details on the impact of addressing this CQ or CC :

Recent analyses suggest that the pool of patients who could benefit from stem cell-based therapies could be as high as 100 million. The actual number of patients receiving stem cell therapies is actually substantially lower than that (< 500,000). it has been postulated that one reason for the gap between the potential patient pool and the actual patient pool has resulted from poor methods of preservation. The failure of recent clinical trials using mesenchymal stem cells support that hypothesis.

Feasibility and challenges of addressing this CQ or CC :

When developing a cellular therapy, supply chain issues (e.g. preservation) is frequently ignored until the failure of a clinical trial. If preservation issues are addressed concurrently with the development of a cellular therapy, the feasibility of addressing the issue is high.

 

There are two critical challenges to addressing this critical challenge: (1) preservation studies are not considered 'sexy' and therefore score poorly in conventional study sections; and (2) organizations developing a cellular therapy do not have a team member with expertise in preservation.

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

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Goal 3: Advance Translational Research

Impactful GH Research to reduce heart, lung, blood, sleep diseases worldwide

We have characterized the risk factors associated with heart, lung, blood, sleep diseases from various papers and reports; what is needed for this information and translation research to be used to reduce morbidity and mortality globally?

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 :

Global reduction of heart, lung, blood, sleep diseases

Feasibility and challenges of addressing this CQ or CC :

Identify and form partnerships with nongovernmental organizations, Ministries of Health and other partners and develop an implementation strategy collaboratively to reduce risk for heart, lung, blood, sleep diseases globally within 10 years. This could use the framework of the previously announced ARRA “Grand Challenges”.

 

Common goals and deliverables between NHLBI and partners will need to be identified

 

Common milestones should be delineated at the outset

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

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10 up votes
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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 3: Advance Translational Research

NHLBI Cohort Populations for T4 Implementation Research

How best can NHLBI observational cohorts be utilized to study observational T4 Implementation Research among both general and vulnerable US populations?

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 :

• Would help identify key factor associated with successful implementation that could be studied in interventional T4 implementation research

• Result would refine implementation strategies and health and social policy aimed to reduce heart, lung, blood, sleep diseases and conditions

• Builds on excellent established platform of research with high quality outcomes in well characterized study populations over long term follow-up.

Feasibility and challenges of addressing this CQ or CC :

• Big data is developing methods to link large data sets from national, state, and community level surveys – surveys that can define exposures to various policies and interventions in place, time, and population.

• A family of high quality cohorts are available for ancillary observation studies

• Collection of community level and more broad policy level exposures is feasible through data already collected and through potentially new data collection.

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

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11 up votes
15 down votes
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Goal 3: Advance Translational Research

T4 Translation Research Informing Early Stage Translational Research

There is a need to utilize insights gained from T4 translation research and implementation science to inform the design and execution of early-stage translational research and clinical trials.

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 :

• Assure that early stage translation research will be suitable for implementation in real world setting

• Aligns the research interventions from T1-T3 research to those appropriate to T4 research

• Potential to focus early stage research in key high burden areas

• Provides research community an understanding of the connections from early stage to late stage translation research which will potentially refine research strategies and directions at all levels

Feasibility and challenges of addressing this CQ or CC :

• Promote the importance of translation to population of heart, lung, blood, and sleep researcher to broader research community

• Potential for more T4 research contributions for guiding investment into translation research from T1-T3

• Provide avenues for T1-T3 investigators to translate their ideas into positive outcomes for population health

• Successful T4 research will stimulate feedback loop and identify opportunities for early translation research

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

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13 up votes
10 down votes
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Goal 3: Advance Translational Research

Funding for synthesis and screening of potentially therapeutic molecules

Currently, there are limited, if none, funding resources to synthesize and screen potentially therapeutic molecules, based on supportive findings in cells, biopsy tissues from the patients with the disease in question, and the preliminary data to support the development of a series of compounds to screen them for their pharmacokinetics, pharmacodynamics, toxicity and use in clinically-relevant large animal models.

Submitted by (@dkagr0)

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

Details on the impact of addressing this CQ or CC :

Although NHLBI-NIH and other institutes emphasize on mechanistic approach, to my knowledge, translation of the findings into the development of novel molecules is rarely pursued in a multi-disciplinary manner. this could have a significant impact on developing better therapeutic and/or management approaches of various diseases.

Feasibility and challenges of addressing this CQ or CC :

In the past, NIH has come up with many RFAs related to this issue. However, one of the major challenges has been the screening of the compounds in a model relevant to human disease. For example, in cardiovascular diseases, about 99% studies are done in mouse models. From genetic studies point of view, this is acceptable, even though now large animals are used for knock-in and knock out gene studies. However, from the screening point of view, an emphasis must be placed on clinically-relevant model, for example, swine, where most of the findings, if not all, could translated to human disease.

Name of idea submitter and other team members who worked on this idea : Devendra K. Agrawal, PhD

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5 up votes
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Goal 4: Develop Workforce and Resources

Training Mentors and Protégés to create a T4 translation pipeline

How can training of investigators (both mentors and trainees) be supported to create a T4 translation research pipeline?

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 :

A robust global T4 translation research community would be developed that would help translate proven-effective interventions for use in populations for a positive health impact

Feasibility and challenges of addressing this CQ or CC :

The NHLBI Global Health and Health Inequities Think Tanks identified T4 translation research as an important area that needs development in the very near future.

 

However, conducting high quality T4 research requires a research community focused in this area. Currently, very few researchers are working in this area. The T4 research community needs to be identified so capacity can be established for conducting T4 research. Incentives would need to be developed to maintain a robust global T4 research community.

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

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Goal 3: Advance Translational Research

Developing Methods and Metrics for T4 Outcomes and Impact

How can methods and metrics capable of conducting high quality T4 research be developed to accurately capture outcomes and the overall impact new T4 knowledge has on population health for heart, lung, blood, sleep diseases and disorders?

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 :

High quality T4 research methods and metrics are needed to move the field of T4 translation research forward while linking large data sets from different sources.

Feasibility and challenges of addressing this CQ or CC :

Demand for high quality methods, metric and evaluation of T4 translation research interest is growing and needs to be addressed immediately to move the field forward.

Recent IOM/NRC studies recommended that the NIH and other research funding agencies support the development of more refined analytic methods and study designs for cross-national health research. These methods should include innovative study designs, creative uses of existing data, and novel analytical approaches to better elucidate the complex causal pathways. The T4 field has some specific metrics including acceptability, reach, adoption, appropriateness, feasibility, fidelity, cost, penetration, and sustainability, each with its standard measurement approach. In addition to a rigorous study design, including these metrics along with population level impact direct measures (e.g., morbidity, mortality) and intermediate measures (e.g. blood pressure reduction) will be critical to assess what has been accomplished and to define success. Finally, measuring the overall impact of new knowledge generated from T4 research is challenging because publication bibliometrics of high impact scholarly journals may not fully capture it.

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

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Goal 3: Advance Translational Research

Developing a Research Community for T4 Translation Research

What incentives will encourage current and new NHLBI investigators to pursue late translation (T4) research of proven effective interventions in heart, lung, blood, and sleep diseases? One of NHLBI’s current strategic plan’s goals is to translate discovery and early translation research knowledge to late stage T4 translation for use in populations so that it has significant positive health impacts and provides a return ...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 :

A robust global T4 translation research community that will implement proven-effective interventions across populations resulting in a significant positive health impact

Feasibility and challenges of addressing this CQ or CC :

The NHLBI Global Health and Health Inequities Think Tanks identified T4 translation research as an important area that needs development in the very near future.

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

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11 down votes
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Goal 3: Advance Translational Research

Develop relevant large animal models for various disease conditions

What is the possibility of investing funds primarily in clinically-relevant models where the findings could be translated in to human diseases?

Submitted by (@dkagr0)

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

Details on the impact of addressing this CQ or CC :

Strong emphasis on the use of a clinically-relevant large animal model would hopefully be more productive in developing better therapeutic approaches and management of patients.

Feasibility and challenges of addressing this CQ or CC :

In view of the lack of facility at many institutions and the cost involved, and the rules and regulations by the USDA and other regularity bodies, special emphasis will be required to build the animal facility at an institution. Where will the funds come from? Similar to many other core facilities set up by the NIH at various institutions, what is the possibility of developing specialized centers for testing a new idea in a clinically-relevant large animal facility?

Name of idea submitter and other team members who worked on this idea : Devendra K. Agrawal, PhD

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Goal 4: Develop Workforce and Resources

Need to train and nurture more "translators"!

One of the major challenges in translating from bench-to-bedside and back is communication: the ability of basic and clinical scientists to understand each other's scientific language to be able to appreciate the importance of the other’s research questions and findings.

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 :

Having an increased number of researchers able to connect dots across the continuum of translational research should increase overall success of translation of ideas into health.

Feasibility and challenges of addressing this CQ or CC :

This requires "rearranging" of already existing elements. Within 5-10 years of running specifically designed re/cross -training programs, the effects might be widely visible.

Basic scientists usually do not keep up with the latest outcomes of important clinical studies, and thus might miss important starting points for new basic research (e.g., negative trials that suggest the need for new hypotheses). The great majority of clinical scientists do not attend basic scientific sessions because are turned off by the specialized (dense/obscure) scientific terms used. Those who are interested in being translators have a hard time integrating and surviving in the "opposite camp" (i.e., at many medical schools, basic scientists are expected to bring in all their salary in a clinical department, and clinicians get little protected time for basic research)

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

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22 net votes
39 up votes
17 down votes
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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

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129 up votes
46 down votes
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