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

Behavioral Interventions Through Modern Technology

What are the effects of behavioral interventions delivered with modern technology and using modern media techniques on changing the habits of adults between age 40 and 60?

Submitted by (@nhlbiforumadministrator1)

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

Feasibility and challenges of addressing this CQ or CC :

Recruit two hundred thousand adults between the ages of 40 and 60 as a laboratory for behavioral interventions delivered with modern technology and using modern media techniques – use the seven habits or similar – provide resources so that the population is representative, encourage the baseline collection of serum samples. Model this on some of the patient center networks funded by PCORI in 2013. Partner with AHA, PCORI, CDC.

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

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10 net votes
21 up votes
11 down votes
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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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7 net votes
11 up votes
4 down votes
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Goal 3: Advance Translational Research

Nucleic Acid Delivery and Gene Editing

For lung diseases, how can new technologies for nucleic acid delivery and gene editing be promoted?

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

Sickle cell disease and fatigue

What factors, other than hemoglobin count, are involved in the extreme fatigue experienced by individuals living with sickle cell disease?

Submitted by (@sicklecellwarrior)

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

Details on the impact of addressing this CQ or CC :

Many in the sickle cell community report continuous fatigue that interrupts their daily activities in spite of normal, or above baseline, hemoglobin levels

Name of idea submitter and other team members who worked on this idea : Sickle Cell Warriors, Inc. community members

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17 net votes
29 up votes
12 down votes
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Goal 3: Advance Translational Research

Addressing Health Inequities through Nontraditional Partnerships

What non-traditional partnerships can be leveraged to address health inequities?

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 :

- Broaden reach to underserved populations

- Increase ability to generate evidence based solutions to address health inequities

- Bring expertise and resources to core partner (NIH)

- Enhance ability to identify unanticipated problems and strengthen efforts across all phases of the implementation research agenda

Feasibility and challenges of addressing this CQ or CC :

Feasibility:

- Increased emphasis on health and health inequities by non-profit and particularly, for-profit organizations

- Affordable Care Act (ACA) includes both general and explicit provisions that could narrow the health disparities gaps through implementation research.

- Can leverage and build upon current research partnerships that exist between government agencies and health care delivery systems to address questions of major public health importance

- Opportune time to employ implementation research addressing health inequities through non-traditional research partnership with sectors such as education, state and local government, transportation (built environment), penal and re-entry systems (health risks and disparities), ministries of health, and for-profits, foundations, and non-profits with health care focus.

 

 

Challenges:

 

 

- Risk of disagreements and friction among partners and management with different priorities

 

- Synchronization of timing for decision making

 

- Achieving partners’ concurrence on decisions that provide the most cost effective solutions

 

- Time needed to establish trust among partners that do not routinely partner to address health inequities

 

- There are limited resources dedicated to fostering Public Private Partnerships

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

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6 net votes
19 up votes
13 down votes
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Goal 3: Advance Translational Research

Enhancing Translational Returns With Better Animal Models and the Basic Science Needed to Support Such Efforts

Can we improve on the preclinical development of therapies through more informed choices on new animal models by linking basic science at the R01 level with national resource centers?

Submitted by (@johnengelhardt)

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 development of effective therapies for heart, lung, and blood require the appropriate animal models for testing. Mouse models have been the mainstay and for the most part very effective. But for those diseases where mice fall short, humans have become the testing ground. With the massive push for translation at NIH, clinical trials often lack proof of efficacy in animal models or are wrongly based on biology in rodents that does not apply to humans. These clinical efforts that don’t effectively translate are exhausting resources to maintain a robust RO1 pipeline on basic research. Recognizing that we must push for translation and also keep basic research funded at a high level, NIH and NHBLI needs to get more creative in taping the best animal models for the disease.

Feasibility and challenges of addressing this CQ or CC :

With new technologies rapidly expanding for transgenesis in embryos, picking the appropriate species for modeling a given disease is now becoming a reality. However, there are several barriers to growth in this area: 1) we often do not know organ physiology and stem cell biology well enough in non-rodent species, 2) the average researcher typically does not have the expertise to utilize non-rodent models in their research or to generate new genetic non-rodent models for study, 3) the costs of non-rodent disease models is high and must be strategically utilized. One potential solution is to maintain resource centers in particular key species that collaborate with basic scientists to both better understand non-rodent organ biology and work selectively to translate basic discovery into therapies. NHLBI recently had an RFA for this type of work that was discontinued. If a new RFA was designed that links funded research (and/or new research applications) through NHLBI to selected target mission diseases and the use of strategic resource centers with expertise in alternative non-rodent models, this might productively transition appropriate use of new models for the next generation of scientists. Such an RFA for example, could provide supplements to existing R01s for projects linked to resource centers and/or have specific R01 RFAs to enter into studies in new animal models or to create new models for a given purpose.

Name of idea submitter and other team members who worked on this idea : John Engelhardt

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31 net votes
48 up votes
17 down votes
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Goal 3: Advance Translational Research

Understanding Chronic Lung Disease Subtypes

What are the subtypes of chronic obstructive lung disease that share a common pathogenesis and can be a basis for precision medicine?

Submitted by (@jdc000)

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

Details on the impact of addressing this CQ or CC :

Chronic Obstructive Pulmonary Disease (COPD) is a complex heterogeneous syndrome. The current approach of regarding this disease as a single entity has limited the ability to develop effective therapies and prevention. Understanding the major subtypes of COPD could lead to more biologically relevant disease classifications, improved prognostic information, and precision medicine treatment.

Feasibility and challenges of addressing this CQ or CC :

The optimal analytical approaches and data types to define complex disease subtypes have not been determined.

Name of idea submitter and other team members who worked on this idea : Ed Silverman, James Crapo and COPDGene Executive Committee

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32 net votes
50 up votes
18 down votes
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Goal 3: Advance Translational Research

Can We Successfully Reduce the Risk Factor Burden and Atherosclerosis in Younger Individuals?

There is growing evidence that risk factors beginning in childhood and young adult life, e.g. from such studies as CARDIA, Bogalusa, etc., are primary determinants of risk of CHD in adults.

Submitted by (@kullerl)

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 levels of BP, lipoproteins, ApoB, obviously obesity, cigarette smoking, and growing risk of early age type 2 diabetes, are epidemic in the young United States population. This may result in a continued high burden of CHD in future generations in the United States. Unless something is done about controlling risk factors in younger individuals, a continued epidemic of CHD is likely.

Feasibility and challenges of addressing this CQ or CC :

The NHLBI should begin clinical trials to determine the best approaches to reducing risk factors in the younger United States population. This should include various studies of environmental modifications, better nutrition studies, improved exercise programs, and identification of host genetic susceptibility. To date, the programs have been remarkably unsuccessful and different approaches are required, especially in lower income and minority populations. The NHLBI should also begin to consider the evaluation of drug therapies for elevated lipids and BP, new drug therapies for obesity and even bariatric surgery in high risk young individuals with initial evaluation of the reduction of subclinical atherosclerotic disease, evidence of myocardial injury, e.g. elevated hs-cTnT, NT-proBNP, etc., in these high risk populations. There is little that the current approaches are very effective.

Name of idea submitter and other team members who worked on this idea : Lewis H. Kuller, MD, DrPH

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21 net votes
46 up votes
25 down votes
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Goal 3: Advance Translational Research

Finding Why Apolipoprotein L1 Gene Variants Increase the Risk for Kidney Failure in African Americans

We plan to find the role of APOL1 in increasing the risk of kidney failure in African Americans and translate this knowledge into preventing end-stage kidney disease and the need for kidney replacement therapy, dialysis or kidney transplantation.

Submitted by (@careygreen)

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

Details on the impact of addressing this CQ or CC :

Increase the quality of life for millions by preventing end-stage kidney disease and thus saving billions of dollars.

Name of idea submitter and other team members who worked on this idea : Carey Green MD, Dollie Green MD

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1 net vote
1 up votes
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Goal 3: Advance Translational Research

Why are CHD Mortality Rates Much Higher in United States Than in Japan or Mediterranean Countries?

There remain very substantial unexplained international geographic variations in the incidence of CHD. Japan, for example, and some of the Mediterranean countries have CHD incidence rates for both men and women that are 1/3-1/4 of those in the United States.

Submitted by (@kullerl)

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

Details on the impact of addressing this CQ or CC :

Migrants from these countries have substantial increase in their CHD rates within a very short time after emigration to the United States or to other countries, strongly suggesting that fundamental genetic differences do not account for these variations in the rates. Reduction of the CHD rates in the United States to those in low risk countries will have the most profound effect on CHD and CVD incidence and mortality.

Feasibility and challenges of addressing this CQ or CC :

Research to further evaluate the probable dietary determinants of these extremely low rates and their implications to the United States should be a high priority. This includes careful study of fatty acids, especially polyunsaturated fatty acids, soy proteins, etc., interrelationships with markers of inflammation and inflammatory diseases. Japan, for example, not only has low CHD rates but also low rates of rheumatoid arthritis (RA), chronic obstructive pulmonary disease even in the presence of high levels of cigarette smoking, multiple sclerosis, all of which would suggest that inflammation may be contributing to these variations in risk of disease. Furthermore, there is growing evidence that omega-3 fatty acids and perhaps other fatty acids may play an important role in T cell function and the development of CVD.

Name of idea submitter and other team members who worked on this idea : Lewis H. Kuller, MD, DrPH

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-8 net votes
10 up votes
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Goal 3: Advance Translational Research

A Pipeline for Investigator- Initiated Translational Science

How might the NHLBI effectively encourage and support its investigators to collaborate with strategic partners to pursue the early translation of their HLBS discoveries into new diagnostics and therapeutics? The critical challenges to effective early translation of discovery science experienced by the investigator community include: 1. The need for translational skills development, training and guidance 2. Need for ...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 :

During the past several decades there have been revolutionary changes in technology that have enabled an unprecedented understanding of basic biologic and pathobiologic phenomena. However, there has not been a concomitant increase in novel technologies to prevent, diagnose, and treat disease. While NHLBI funds thousands of R01 grants that support mechanistic research, only a small percentage moves the basic discoveries into the pre-clinical space, a critical step in fulfilling NHLBI’s mission. An analysis of the Division of Blood Diseases applications for the FY 2012, showed that while 32% (174/541) of the unsolicited applications (RO1, R21, PO1) had at least one early translational component, only 15% went beyond proof of concept and only 3% included early phase clinical trials. Patent filings, a main gateway to translation, are another way to estimate the translation of NHLBI discovery science. A survey of 90 NHLBI investigators, randomly selected across all three Divisions, found 76% of the investigators had no patent activity over a 10 year period and 12% accounted for 82% of all the patent activity. These data suggest that there may be barriers to investigators being able to realize the translational potential of promising discoveries beyond proof of concept. NHLBI needs an overarching, coordinated, and efficient plan to encourage and support investigators in their independent pursuit of translational research.

 

The creation of an integrated, facilitative programmatic pathway at NHLBI that would leverage existing NIH resources to ease the major barriers to translation of scientific discovery in the investigator community by:

•Providing skills development training and guidance for investigators wishing to do translational research

•Coordinating the support of all pre-IND phases of translational science

Facilitating reproducible pre-clinical research in animals, including animal and humanized models, medical chemistry, pharmacological toxicology

•Providing support for early phase or adaptive design clinical trials

•Ensuring scientific review that is available and tailored to all phases of investigator-initiated translational science

•Establishing a robust system for ongoing portfolio analysis and program evaluation as well as metrics for evaluating programmatic outcomes

 

The creation of an integrated, facilitative programmatic pathway at NHLBI that would leverage existing NIH resources to ease the major barriers to translation of scientific discovery in the investigator community by:

•Providing skills development training and guidance for investigators wishing to do translational research

•Coordinating the support of all pre-IND phases of translational science

Facilitating reproducible pre-clinical research in animals, including animal and humanized models, medical chemistry, pharmacological toxicology

•Providing support for early phase or adaptive design clinical trials

•Ensuring scientific review that is available and tailored to all phases of investigator-initiated translational science

•Establishing a robust system for ongoing portfolio analysis and program evaluation as well as metrics for evaluating programmatic outcomes

Feasibility and challenges of addressing this CQ or CC :

The overwhelming response to NHLBI translational initiatives suggests a critical mass of investigators willing and able to explore the translational potential of their discoveries. The barriers to the continuous receipt of translational applications outside of the RFA mechanism have been identified and the proposed model for a competitive peer-reviewed process that spans the early translational pipeline has already been successfully implemented in at least one other NIH Institute. Adopting this model, the pipeline, as envisioned, would mostly consist of facilitative PAs and Review would not require a major up front expenditure of NHLBI targeted funding.

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

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196 net votes
226 up votes
30 down votes
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