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

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

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

Asthma-COPD overlap syndrome

Approach, diagnostics and management of asthma-COPD overlap syndrome.

Submitted by (@nhlbiforumadministrator)

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 : Asthma and Allergy Foundation of America (AAFA)

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

Predicting COPD exacerbations and relapse

What measures other than PFT data can be used to predict risk of 1) COPD exacerbations (e.g., hospitalization, urgent care visit, or ED visit for COPD exacerbation) or 2) relapse (e.g., re-hospitalization, urgent care visit, or ED visit) following hospital discharge after treatment of COPD exacerbations?

Submitted by (@k.willard)

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

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14 net votes
16 up votes
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Goal 3: Advance Translational Research

Achieving Transplantation Tolerance in Recipients of Heart and Lung Allografts

Despite improvements in the early post-transplant survival of thoracic organs, registry data show that the graft half-life is only 11 years for heart recipients and 5 years for lung recipients. Infection accounts for 33% of cardiac and 40% of lung transplant recipient death between day 31 and one year post transplant. After 5 years, cardiac allograft vasculopathy (30%), and malignancy (23%) cause most cardiac recipient ...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 :

Induction of immune tolerance is the ultimate goal in the field of organ transplantation, to eliminate the need for chronic immunosuppression and prevent chronic rejection. Tolerance of kidney allografts has been achieved in non-human primates (NHPs) and in humans by using a combination of nonmyeloablative conditioning and donor bone marrow transplantation that results in mixed chimerism, but this method fails to induce tolerance in heart recipients. The reasons for these organ-specific differences are not clear. However, the strength and nature of the immune response to a particular organ varies within and between transplanted organs. In most experimental transplant models, kidney/liver allografts can actively participate in the induction and maintenance of tolerance and evoke a weaker rejection response than heart/lung allografts, which are, for the most part, “tolerance-resistant.”

Understanding the immunological mechanisms underlying these organ-specific differences is critical to extending tolerance to recipients of tolerance-resistant organs such as hearts/lungs. Preliminary data suggests that cells or cell products intrinsic to kidney/livers but not heart/lung allografts promote the induction of tolerance by activating and/or expanding host regulatory T cells. The Critical Challenge is to identify these specialized cells or cell products, elucidate their mechanism of action, and then apply that knowledge to robust protocols capable of inducing allograft tolerance.

Feasibility and challenges of addressing this CQ or CC :

Long term tolerance has already been achieved in human kidney recipients. Encouragingly, long term tolerance has been achieved in nonhuman primate heart and lung recipients using experimental protocols. Thus, the feasibility of successfully inducing tolerance in human heart and lung recipients is real.

Name of idea submitter and other team members who worked on this idea : Joren C. Madsen, MD, Dphil

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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
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Goal 3: Advance Translational Research

Translating cardiac development/genetics knowledge into therapy

What is needed to translate our knowledge of cardiac development and congenital heart disease genetics into novel diagnostic and/or therapeutic strategies for congenital or acquired heart disease?

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 :

Develop new therapies for congenital or acquired heart disease.

Feasibility and challenges of addressing this CQ or CC :

We are poised to take advantage of the incredible advances in our understanding of cardiac development and genetics which have resulted from the development of high throughput technologies.

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
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Goal 3: Advance Translational Research

Translation of novel computed tomography technologies

Computed tomography and related x-ray imaging techniques are mainstays of cardiovascular imaging and treatment. Novel technologies are emerging for CT that promise further improvements for cardiovascular disease, such as spectral CT, phase contrast CT or nanoparticle contrast agents. However, many challenges remain for their translation to patients.

Submitted by (@davidcormode)

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

Details on the impact of addressing this CQ or CC :

Spectral and phase contrast CT promise enhanced diagnoses of cardiovascular disease due to their improved soft tissue contrast and increased sensitivity towards contrast agents. Novel contrast agents are starting to allow molecular imaging with CT. These technologies could allow sophisticated characterization of atherosclerotic plaque and other diseases. This would provide enhanced diagnoses, tailored treatments and monitoring of response to therapies.

Feasibility and challenges of addressing this CQ or CC :

Improvements and innovations need to be made in beam filtration, detector systems, electronics and image reconstruction algorithms to allow clinical versions of spectral and phase contrast CT systems to be developed that have similar performance in terms of speed and radiation dose of current clinical systems. Investments need to be made in the development of novel, targeted nanoparticle contrast agent materials and studying their safety prior to clinical trials. While these are very significant challenges, with innovative approaches it should be possible to overcome these problems.

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

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Goal 3: Advance Translational Research

Using Single Patients for Clinical Trials

To foster the IOM recommendation that every healthcare encounter contribute to a learning healthcare system, would clinical practice structured as N-of-1 trials and documented via EHR/EMR provide strong practice-based evidence?

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 : NHLBI Staff

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Goal 3: Advance Translational Research

The "Metagenome"

How could we best understand the interplay within the metagenome (the nuclear (nDNA), mitochondrial (mtDNA), and microbiome DNA), and between the metagenome and environment as a cause for individual variability, including susceptibility to disease and therapeutics? Could the genomic “chimerism” possibly be related to reported sex differences in HLBS diseases? • Most factors needed for mitochondria are encoded by nDNA. ...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 :

Would allow understanding the basis for complex individual variations beyond the current focus on the nuclear genome

Feasibility and challenges of addressing this CQ or CC :

Feasible in 10 years.

For example, the issue of “chimerism” between mtDNA and nDNA is intriguing: every cell, male or female, contains mtDNA and mitochondria of female (maternal) origin. Mitochondria are cell’s main energy engine, essential in all cells with high energy expenditure, such as myocytes, but mitochondria are also emerging as a major source of pathogenic reactive oxygen species in connection with a variety of heart, lung, blood, sleep diseases.

 

 

High complexity requires researchers working across discipline boundaries, big data science, modeling

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

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Goal 3: Advance Translational Research

Impact research related to obesity interventions in black and and other high-risk populations?

How can we increase high-impact obesity and CVD-related intervention research with black and other high risk populations. Specifically, how can the NHLBI and NIH process ensure the generation of more research on solutions to weight issues that is goal-oriented and population-focused, e.g., sets of studies designed to align with a coherent, population-focused research agenda with prioritized questions based on potential ...more »

Submitted by (@skumanyi)

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 high and above-average prevalence of obesity and severe obesity among black children and adults persists, and obesity prevalence is still increasing in some age and gender subgroups in the black population. Current treatments don’t seem to work as well to reduce weight in blacks compared to whites (at least based on studies in adults), although some show promise for reduction of CVD risk factors even with modest weight loss. Preventive interventions are urgently needed but underdeveloped.

 

The context and process of intervening on weight issues differs by cultural and socioeconomic contexts. Yet, research that specifically focuses on approaches that can be effective in black population subgroups in communities at large is sparse; many studies are small, with methodological limitations. Within the overall research effort to address obesity, more studies, better studies, and coordinated studies on black Americans as a high risk sub-population could move the needle. This could be a general need related to high-risk populations who will never be the mainstream research focus and may have different contexts and needs.

Feasibility and challenges of addressing this CQ or CC :

It is feasible to do this if the challenges can be overcome and appropriate funding mechanisms are provided. The typical funding mechanisms focus on investigators rather than on populations and on disconnected R01s. The likelihood that these will add up to tell a coherent story is low. More mechanisms are needed to support coordinated studies planned to have collective impact for the black (or other) population. Other challenges are to improve methodological quality (including design, measurements, and duration), phase studies so that they can build on each other, and standardize process and outcome assessments to improve the ability to synthesize study results.

Name of idea submitter and other team members who worked on this idea : Shiriki Kumanyika and members/colleagues who are authors of a journal supplement to Obesity Reviews, October 2014

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6 net votes
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Goal 3: Advance Translational Research

Congenital Heart Disease (CHD) Screening Access

What is needed to improve access to quality neonatal health care in order to get a more accurate idea of CHD prevalence in children, especially in underrepresented populations and those with limited access to primary care?

What role could safety net programs and community health centers play with screening (and subsequent treatment, education)?

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 :

More accurate CHD prevalence numbers, especially in underrepresented populations and those with limited access to healthcare.

Feasibility and challenges of addressing this CQ or CC :

Agreement on CHD screening practices/standards.

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

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6 up votes
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