Goal 3: Advance Translational Research

Genome Profiling

How can proper infrastructure be designed to host sequencing data from hematologic diseases so as to enable its efficient interpretation and use in clinical care?

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

Details on the impact of addressing this CQ or CC :

Accurate and consistent analysis of genetic data is crucial for both basic research and clinical applications, however, the complexity of sequence mutations in several blood disorders as well as the immense amounts of raw data produced during the sequencing and analysis process, make accurate bioinformatics analysis a challenge. Furthermore, the lack of consistency in the analysis of the non-coding genome and variations in correlating this information with transcriptional and epigenetic data pose an additional challenge in obtaining a comprehensive portrait of various hematologic diseases. To overcome these challenges, content-rich portals that can offer cost-effective and regulated access to raw genomic data for interrogating and sharing sequencing results without compromising patient privacy must be designed. Also, the biologic and clinical relevance of genetic alterations found in these portals must be reliable and sufficiently comprehensive in order to foster proper interpretation.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology (ASH)

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-8 net votes
10 up votes
18 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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-5 net votes
11 up votes
16 down votes
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Goal 3: Advance Translational Research

Next Stage of COPD Discovery

1) Refinement of COPD subphenotypes for therapeutics, diagnostics and mechanistic interrogation. The NIH should encourage a strong focus on a) rigorous, mechanistically-reinforced definitions (chronic bronchitis, emphysema (with and without obstruction), frequent exacerbators, combined pulmonary fibrosis and emphysema) and 2) the development and optimization of animal model systems that replicate the different subphenotypes. ...more »

Submitted by (@lungmatbio1)

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

Details on the impact of addressing this CQ or CC :

If we could develop less costly and time consuming cell and animal models of COPD that reflect meaningful subphenotypes, we would be able to not only probe basic mechanism but also have reliable test platforms for candidate therapies.

There is typically a major obstacle between the acquisition of big data from observational disease cohorts, often broad but superficial, and the translation of these findings to basic discovery efforts. The clinical researchers speak a different language than the basic investigators and traversing this chasm with grant enticements might prove helpful.

Feasibility and challenges of addressing this CQ or CC :

This would require some suspension of the classic mechanistic, hypothesis driven proposals to develop these research tools.

There would need to be some reconstruction of study sections to permit these combined clinical-basic grants. The translational PPG was in keeping with this but should be reinforced with smaller grant programs such as RO1 level grants.

Name of idea submitter and other team members who worked on this idea : lungmatbio1

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16 net votes
26 up votes
10 down votes
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Goal 4: Develop Workforce and Resources

Enhancing T4 Implementation Research Expertise

We need to increase our base of T4 implementation research expertise among researchers, reviewers, and investigators.

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 :

Increase our base of expertise in a relatively new field. Increase the number of funded grants and projects that include T4 implementation research.

Feasibility and challenges of addressing this CQ or CC :

Additional training for T4 implementation research can be added to the training infrastructure currently in place at the NHLBI/NIH.

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

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-6 net votes
4 up votes
10 down votes
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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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-1 net votes
7 up votes
8 down 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

Voting

15 net votes
27 up votes
12 down votes
Active

Goal 3: Advance Translational Research

Implementation of T4 Translation Research Platforms and Networks

How can cost-effective implementation of late stage translation (T4) research protocols be facilitated for heart, lung, blood, sleep diseases and health inequities?

Can research platforms and networks be created and utilized to facilitate execution of multi-level interventions and approaches for the end user in collaboration with key stake holders?

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 :

Answering this question would lead to timely implementation and dissemination of new knowledge that will be available to address the current heart, lung, blood, sleep health burden.

One of NHLBI’s current strategic plan’s goals is to translate research knowledge for use in populations so that it has significant positive health impacts and provides a return on investment from discovery and early translation research. Currently, only a fraction of new knowledge yielded from proven effective early stage translation research is being used in the real world – resulting in an avoidable disease burden. Late stage translation (T4) research studies the implementation of proven-effective interventions at a multi-level to include populations, communities, healthcare systems, providers, families and patients. Conducting T4 research requires development of comprehensive research teams across communities, public health and health care delivery systems, families, and patients along with unique translation T4 research methods and metrics. Because resource intensive infrastructure is needed to conduct high quality T4 research and this infrastructure is not widely or readily available, a platforms and network for conducting protocols will prove efficient and provide high quality standard outputs.

Feasibility and challenges of addressing this CQ or CC :

The NHLBI Health Inequities Think Tank highly recommended that creating T4 translation research platforms and networks would meet the needs of the scientific community enabling them to respond to the heart, lung, blood, sleep health burden.

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

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4 net votes
13 up votes
9 down votes
Active

Goal 3: Advance Translational Research

Genome Editing and Gene Therapy

There is a critical need for the establishment of strategies that will determine the efficacy, safety, and toxicity of genome editing techniques specifically in hematologic diseases.

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

Details on the impact of addressing this CQ or CC :

Inherited monogenic hematologic diseases such as hemophilia, beta-thalassemia and sickle cell disease are prime targets for future application of genome editing technology. However, studies are still needed to advance our understanding of the biology of genome editing as well as determine which other disorders are amenable to genome editing correction. Emphasis on preclinical research that focuses on determining the accuracy, safety and efficiency of this technology in order to help minimize off-target mutations and reduce toxicity, is essential for effective translation of this technology into the clinic. Once preclinical efficacy is established, support will be needed for clinical vector production, toxicity testing of the vectors/reagents used, and the performance of clinical trials. The gene correction strategies developed for inherited disorders will also be attractive for other hematologic diseases, and autoimmune disorders like lupus, rheumatoid arthritis, and type I diabetes). There is also a critical need for supporting preclinical validation studies, scale-up and GMP cell manufacturing, all of which could be shared infrastructures across multiple diseases in the NHLBI portfolio.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology (ASH)

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69 net votes
87 up votes
18 down votes
Active

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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-7 net votes
6 up votes
13 down votes
Active

Goal 3: Advance Translational Research

Leveraging Networks of Federally Qualified Healthcare Centers

How best do we leverage the existing Federally Qualified Healthcare Center’s (FQHC) infrastructure to study T4 Implementation Research for heart, lung, blood, sleep diseases and conditions among high risk and vulnerable 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 :

• Develop strategies to reduced Health Inequities

• Potentially be scaled up across an entire health system with huge population impact

• Studies would be done in the environment and context where the findings with be implemented leading to better uptake and sustainability.

Feasibility and challenges of addressing this CQ or CC :

• Formative FQHC groups are already being organized but do not have strong leadership and support

• FQHCs have ready access to the high risk and vulnerable populations that would benefit most from the research

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

Voting

-14 net votes
7 up votes
21 down votes
Active

Goal 1: Promote Human Health

Transforming Transplantation with RISC

What is necessary to reprogram the immune system to improve transplant outcomes of hearts, lungs, and hematopoietic cells? 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 ...more »

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 :

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

Voting

-3 net votes
15 up votes
18 down votes
Active

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

Voting

3 net votes
13 up votes
10 down votes
Active