Goal 3: Advance Translational Research

The Investigator's Catch-22: How Can NHLBI Help?

The Critical Challenge is to determine how NHLBI can continue to foster the translational research necessary to allow our researchers to further develop their NHLBI-funded basic science discoveries. Researchers can't readily get a "typical" grant to perform the preclinical and early clinical translational IND-enabling research, and also can't yet attract private sector support without having done the work to "de-risk" ...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 :

Ensuring that NHLBI-funded researchers have the means to further develop promising research discoveries will ensure that NHLBI continues to fulfill its Mission. Providing funding or resources to move basic science discoveries from the lab towards the clinic can expand the research environments, opportunities, and collaborations available to NHLBI investigators and lead to potential new therapies for heart, lung, and blood diseases.

Feasibility and challenges of addressing this CQ or CC :

Just as research project itself can take years, if not decades, to accomplish, so too can a cultural shift in our extramural research community. While one may have a different understanding of what constitutes "translational" research depending upon his or her vantage point, in reality it is bi-directional (from bench to bedside and back to bench) and offers possibilities for a wide range of researchers. Engaging established basic scientists in translational research can open new opportunities to them, and younger researchers are likely more familiar and well-poised for new research paradigms and collaborative efforts such as those afforded by the translational development process.

Basic discovery science is appropriately the backbone of the NHLBI extramural research program. But, for any basic science discovery to have a meaningful impact on human health, it must be "translated from the bench to the bedside." These next steps in translation involve a tremendous amount of research that is not amenable to hypothesis-driven grant mechanisms like an R01 or P01. Without access to funding support for early-stage translational work, investigators can be stymied and NHLBI-funded basic science discoveries can languish.

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 animal models of lung transplantation.

Lung transplantation as a cure for terminal lung disease has seen little improvement in outcomes for more than 20 years. The field remains highly challenging, in part, because of an absence of robust animal models which are technically- feasible and reproducible across centers. Further, models have limited relevance to clinical (chronic) airway remodeling, the leading problem in pulmonary allografts. In the absence of ...more »

Submitted by (@mnicolls)

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 critical challenge is to address the leading problems facing lung transplant patients through the creative application of multiple technological platforms employing all available pre-clinical models by multiple NIH investigators. With greater focus on the deeper development of existent models, the delineation of their strengths and limitations and importantly, cooperation between Academic Centers, efforts can be optimized to improve outcomes for a condition that has enjoyed little benefit from basic research.

Feasibility and challenges of addressing this CQ or CC :

The siloed nature of much clinical and experimental lung transplantation research limits progress and broader initiatives. With specific respect to developing animal models of lung transplantation, the general lack of consensus about the suitability of the techniques employed at different institutions stifles progress. A strategic vision, guided by leaders across the field, highlighting benefits and limitations of current animal models can be coupled with a consensus statement about the most pressing issues in lung transplantation worthy of increased investigation.

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

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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 3: Advance Translational Research

Animal Models for Translational Research and Drug Development

There is a need to identify and develop suitable animal models (e.g. larger, non-primate animal models) that faithfully predict the outcomes of new medicines and treatments in heart, lung, blood, and sleep (HLBS) disorders prior to human 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 :

If animal models can faithfully predict the outcomes in human clinical trials of new medicines and treatments, it will reduce the economic burden for the failure of drug development.

Feasibility and challenges of addressing this CQ or CC :

Identification of current available animal models;

Development of new animal models with recent advances in mammalian genome projects and gene targeting technologies could be done over the next 5-10 years

Medical research, especially in basic discovery, has benefited significantly from the use of various animal models, such as gene-targeted and transgenic mouse models. However, many discoveries from animal models (e.g. mouse models) failed to translate into human applications.

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

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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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Goal 3: Advance Translational Research

Roadblocks to discovery and translation in lymphoma

What are the central infrastructure and research roadblocks that are preventing transformational discoveries in lymphoma

Submitted by (@dweinstock)

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

Details on the impact of addressing this CQ or CC :

Outlined in the attached manuscript published by a committee of experts organized by the American Society of Hematology

Name of idea submitter and other team members who worked on this idea : David Weinstock for the Steering Committee of the 2014 ASH Meeting on Lymphoma Biology

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Goal 3: Advance Translational Research

Translation Research Dissemination & Implementation Frameworks

We need to identify and test the proven effective dissemination and implementation frameworks that are relevant to heart, lung, and blood disorders in order to scale up evidence-based interventions in real world settings, ultimately improving health equity among minority populations, including low income minority residents living in public housing.

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 :

• Ability to determine how much of an evidence based intervention can be sustained in real world settings.

• Add utilization of D&I frameworks to researcher’s core competency training skills.

• Promote long term sustainability of evidence based interventions.

Feasibility and challenges of addressing this CQ or CC :

• Researchers from the 2014 NIH’s Annual Conference on the Science of Dissemination and Implementation: Transforming Health Systems to Optimize Individual and Population Health presented compelling evidence that dissemination and implementation frameworks are an effective means to scaling up evidence based interventions.

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

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Goal 2: Reduce Human Disease

Interactions between anticoagulant therapy and antiretroviral drugs

Cardiovascular pathology has become a major problem in the management of the HIV-infected patient during the ART era. A large number of HIV patients will receive anticoagulants drugs for secondary prevention of cardiovascular disease. It is therefore critical to understand the interactions between antiretroviral therapy and anticoagulant therapy to safely treat HIV patients.

Submitted by (@pandrea)

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

Details on the impact of addressing this CQ or CC :

With over 50% of HIV-infected patients in the US anticipated to be > 50 years of age by 2015, the overall risk of CVD will be significantly higher and could become the main challenge for the management of chronic HIV infection. A large number of HIV-infected patients with CVD will therefore need treatment for primary and secondary prevention of atherothrombotic events. The secondary prevention of CVD almost invariably includes prescription of one or multiple anticoagulants drugs. It is therefore conceivable that anticoagulant therapies will be frequently associated with ART for the management of HIV patients, which already developed CVD. The interactions between these therapies are not well studied and are critical for the management of the HIV-infected patients.

Feasibility and challenges of addressing this CQ or CC :

Feasibility: 1) retrospective studies on a large number of HIV patients that had cardiovascular events and were treated with antiretroviral drugs; 2) prospective studies comparing different antiretroviral regimens associated with the most current anticoagulant therapy recommended for secondary prevention of CV disease; 3) use of animal models of AIDS for testing new anticoagulants and the interaction with the antiretroviral drugs.

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

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Goal 2: Reduce Human Disease

Rare disease therapeutics high throughput screening

Can we develop model systems for the high throughput screening of new and existing agents as possible therapies for rare diseases?

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 1: Promote Human Health

Promoting the Development of Animal and Cellular Model Systems

NHLBI might consider creating incentives for the development of core labs and national facilities to promote development of animal and cellular model systems that mimic lung injury, repair, and regeneration.

Submitted by (@skrenrich)

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 : Cystic Fibrosis Foundation

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Goal 2: Reduce Human Disease

Biology of the intact alveolar wall – the new frontier in lung research

HOW DO WE STUDY THE BIOLOGY OF THE INTACT ALVEOLAR WALL IN THE CONTEXT OF LUNG DISEASE AND REPAIR?

Submitted by (@jb3900)

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

Details on the impact of addressing this CQ or CC :

SEE UPLOADED FILE

Feasibility and challenges of addressing this CQ or CC :

SEE UPLOADED FILE

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

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Goal 3: Advance Translational Research

Facilitating the translation of discovery science into proof of concepts in preclinical models

What steps can the research community take to facilitate the translation of discovery science into proof of concepts in preclinical models and in humans for diagnosis, prevention, and treatment? • Current regulatory environment • Lack of communication between discovery and clinical research worlds • Lack of training • Getting industry, academia, and NHLBI to partner; and the business model to make it happen. • Limited ...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 :

• Increased number of novel therapeutics, diagnostics and devices in early phase clinical trials

• Increased impact in rare diseases and unmet needs

• Increased number of licensed IPs from academic centers

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

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