Showing 19 ideas for tag "models"

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?

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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-18 net votes
8 up votes
26 down votes
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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

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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-4 net votes
8 up votes
12 down votes
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Goal 2: Reduce Human Disease

New analysis methods for research using animal models

The idea that 'animal models can faithfully predict the outcomes in human clinical trials of new medicines and treatments' is highly compelling. However, due to differences (biological and non-biological) between humans and animals this goal can likely not be achieved. Not only are animals genetically different from humans, everything else is different too. Even if living quarters are shared (e.g. house pet animals),... more »

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

Details on the impact of addressing this CQ or CC

Because of the differences between humans and animals, a different paradigm of expectations and analysis methodology needs to be developed. Animal models (natural and man-made) have been superbly informative for developing means to improving human health. The key to 'successful animal models' is the interpretation of the data - and the careful design of the animal studies to capture one of the essential molecular, environmental, behavioral problems that cause the human disease and to model the essential problem in the animals.

Feasibility and challenges of addressing this CQ or CC

At the moment, the specific design of animal models and the interpretation of the data is in the hands of individual scientists. Specific guidelines could be developed for every aspect of animal experimentation and this would help to optimize the output with respect to understanding the next steps: e.g. is this data useful in basic science, in translational science, which questions need to be answered using the analysis of human individuals ? The availability of specific methods will allow us to better move between bedside to bench and back.

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

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-12 net votes
7 up votes
19 down votes
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Goal 3: Advance Translational Research

Neglect of Valuable Heart Health Data

Routine bypass surgery generates left ventricle pressure and volumetric flow data which can be modeled by estimated parameters capable of determining a heart health index. This capability is also available online for the surgeon's

guidance and is applicable to any heart chamber.

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

Details on the impact of addressing this CQ or CC

A comprehensive heart health state would be established

Feasibility and challenges of addressing this CQ or CC

The theory has been proven multiple times, intellectual and political inertia are the roadblocks.

Name of idea submitter and other team members who worked on this idea William ONeill, Jeffery Shuhiaber

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-6 net votes
4 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.

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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-6 net votes
5 up votes
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?

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 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.

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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-1 net votes
3 up votes
4 down votes
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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?

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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2 net votes
2 up votes
0 down votes
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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.

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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2 net votes
5 up votes
3 down votes
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Goal 3: Advance Translational Research

Animal models of vascular diseases

How can we better model human vascular disease in all its complexity?

­This is key to more effective translation of both diagnostics and therapeutics. Develop improved animal models of vascular diseases including PAD, aneurysm, venous diseases, to facilitate fundamental research and preclinical development.

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 Society for Vascular Surgery

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2 net votes
3 up votes
1 down votes
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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.

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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4 net votes
13 up votes
9 down votes
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Goal 3: Advance Translational Research

Molecular determinants of vascular wall development and aneurysm formation that can be used as markers for early diagnosis

To increase the potential of translating basic research discoveries into the clinic, there is a need to discover molecular biomarkers that confer risk for aneurysms and vascular dissections. The creation of a nation-wide biorepository of well-defined tissue and plasma samples along with research utilizing these tissue samples employing state-of-the art proteomics, genomics and development of appropriate mouse models will... more »

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 challenge is the coordination of all components of the Project (i.e. development of a national biorepository along with coordination of proteomics and genomics analysis as well as proof of concept in animal models).

Feasibility and challenges of addressing this CQ or CC

This process is not feasible via the R01 funding mechanisms. The feasibility of addressing this critical challenge is excellent provided adequate resources are provided.

Name of idea submitter and other team members who worked on this idea Dudley Strickland and Selen Catania Muratoglu

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5 net votes
7 up votes
2 down votes
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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 »

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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10 net votes
21 up votes
11 down votes
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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 »

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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5 net votes
15 up votes
10 down votes
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