Showing 8 ideas for tag "mechanisms"

Goal 1: Promote Human Health

What administrative changes might facilitate team science? Update peer-review and budget mechanisms for team science.

NIH peer-review methods were developed at a time when biomedical science was generally conducted by individual investigators. Approaches to defining conflict of interest in peer review that worked well for individual investigators may not be fit for the review of large-scale collaborative projects. Similarly, the subcontract mechanisms are often slow and cumbersome at a time when projects need to be nimble and timely.... 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

Promote team science.

Feasibility and challenges of addressing this CQ or CC

Some of the policies are NIH or government wide, but the problems of peer review and subcontracting mechanisms need to be addressed

Name of idea submitter and other team members who worked on this idea Psaty & Tracy

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Goal 2: Reduce Human Disease

RFA on EC-cardiomyocyte interactions in the mechanisms and treatments of cardiovascular diseases

Often under recognized, the cardiac endothelial cells are highly abundant in the heart, and may have important roles in modulating cardiac function, besides simply serving as structural component of blood vessels. Evidences of ours and others have indicated an emerging role of cardiac endothelial cells signaling to cardiomyocytes to mediate important pathophysiological responses. Nonetheless, detailed mechanisms 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

Successfully addressing this question would no double reveal novel mechanisms and ways of monitoring treatment responses of cardiovascular disease, ultimately leading to novel drug targets, valuable biomarkers and extended new directions of basic research as well.

Feasibility and challenges of addressing this CQ or CC

Tools of studying these cells are mostly available. Both adult cardiomyocytes and endothelial cells from the heart can be isolated and cultured, although cardiomyotyes need to used within 24 hrs and cannot be passaged. However successful preparation of these cells from WT and transgenic animals would permit co-culture experiments and mechanistic studies. These cells can also be studied using in-situ techniques either detecting molecular changes/events or dynamic interactions. Potential challenges would side in selective targeting of these cells, for example, either ECs or cardiomyocytes, once a potential therapeutic is in the testing. Nonetheless, PECAM-ab conjugated techniques have been employed to specifically deliver proteins to endothelial cells, so I am confident most of the challenges can be worked out, particularly within a RFA awardees group with frequent exchanges of ideas.

Name of idea submitter and other team members who worked on this idea Hua Linda Cai, University of California Los Angeles

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27 net votes
30 up votes
3 down votes
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Goal 2: Reduce Human Disease

Triggers of cellular and molecular pathway decompensation during pulmonary exacerbations.

What triggers decompensation of cellular and molecular pathways during exacerbations of chronic lung diseases?

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

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Elucidation of molecular and cellular pathways driving and sustaining exacerbations in chronic lung diseases. Specifically, (1) discover what perturbs antecedent conditions precipitating mal(adaptive) compensatory mechanisms leading to pulmonary exacerbation including impact of heterogeneous resilience and concomitant chronic diseases and (2) clarify response heterogeneity of longitudinal molecular and cellular signature during treatment and recovery.

Feasibility and challenges of addressing this CQ or CC

Longitudinal pulmonary exacerbation research nested with clinical care can be initiated within 1-2 years. As part of clinical care leveraging digital education/data (electronic health/medical records and attendant meaningful use requirements), an N-of-one research design could become self-sustaining within health care systems.
Pulmonary exacerbations exhibit multiple pathogenic pathways various concurrent pathophysiological pathways, and diverse clinical manifestations. Prevention and treatment of pulmonary exacerbations is hampered by this complex biology that is dynamic and appears to vary during the course of exacerbations. Progress toward precision medicine for exacerbations may require organization of a new taxonomy for disease, which reflects a set of clinically meaningful and exploitable similarities and differences between disease traits (exacerbation polypathomics).

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

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13 net votes
23 up votes
10 down votes
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Goal 2: Reduce Human Disease

Mechanisms of Uterine Hemostasis

What are the mechanisms of uterine hemostasis?
Endogenous mechanisms of uterine hemostasis protect women from the bleeding challenges of miscarriage, childbirth, and menstruation. Dysregulation of these mechanisms has implications for the critical public health problems of hormonally-induced venous thromboembolism and hormonally-induced arterial thromboembolism (myocardial infarction and stroke). Our current understanding... more »

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

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Urgent clinical questions hinge on understanding the mechanisms of hormonally-induced thrombosis – questions about how women with various underlying cardiovascular conditions, hematological conditions such as sickle cell disease, and endocrinological conditions such as obesity are differentially affected by endogenous and exogenous hormones.

The additional impact of identifying the mechanisms of uterine hemostasis is potentially improving the global health problem of maternal and gynecological hemorrhage. If there is failure of normal uterine hemostasis after childbirth there is the potential for massive postpartum hemorrhage. If there is failure of normal hemostasis during the menstrual cycle there is the potential for acute heavy menstrual bleeding (acute menorrhagia).

Feasibility and challenges of addressing this CQ or CC

An understanding of the mechanisms of uterine hemostasis provides the basis for understanding hormonally-induced thrombosis and vice versa. The paradigms of pregnancy; assisted reproductive technologies; contraception; and postmenopausal hormone replacement provide four clinical scenarios across the life cycle where female hormones or their synthetic counterparts provide opportunities for insight into mechanisms of hormonally-induced thrombosis. The NIH/NHLBI can and should support studies that elucidate the mechanisms of uterine hemostasis and hormonally-induced thrombosis and should make such studies a scientific priority. The NIH/NHLBI has the capacity and resources. Studies would include basic science, translational and clinical studies. Although studies would benefit from the participation of other institutes and from the contribution of multiple disciplines, NHLBI should take the lead.

Research efforts should be accompanied by cross-disciplinary training opportunities. The Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) program is a mentored career development program which connects junior faculty to senior faculty with shared research interests in either women’s health or sex differences research. Junior faculty are supported by institutions who receive grants from the Office of Research on Women's Health (ORWH) and BIRCWH program co-sponsors – multiple institutes which as yet do not include the NHLBI.

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

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19 up votes
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Goal 4: Develop Workforce and Resources

Research training to support population-focused obesity research in ethnic minority populations

NIH is already facing a challenge in increasing the number and viability of researchers of color. Obesity research in black (or other high risk minority) populations can be used to explore how research training programs that focus on specific issues of importance to populations of color might contribute to the recruitment and success of ethnic minority researchers in the NIH system.

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

Details on the impact of addressing this CQ or CC

To say the least, not all researchers of color study disparities related issues and not all disparities research is done by researchers of color. That is the way it should be. However, I suspect that research focusing on populations of color would attract a greater than average proportion of researchers of color (NIMHD might have data on this but NIMHD funding alone would be grossly insufficient as the only relevant funding stream. It would also be inappropriate and ineffective to silo the entire burden as an NIMHD responsibility).

Feasibility and challenges of addressing this CQ or CC

The infrastructure for such training might not exist. Isolated minority researchers attached to various centers and programs would not necessarily work; some sort of networking would have to be done based on an infrastructure devoted to population-oriented obesity research and with a critical mass of obesity researchers focusing on the black (or other) population..

Name of idea submitter and other team members who worked on this idea Shiriki Kumanyika, Melicia Whitt-Glover, Debra Haire-Joshu

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6 up votes
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Goal 2: Reduce Human Disease

What is the effect of variant genes on AVM development in HHT

Natural genetic variation between individuals can influence the outcome of carrying an HHT mutation. Some gene variants may be protective while others may increase the risk of AVM or telangiectasis. By identifying the variant genes that alter risk of AVM may give clues to the molecular mechanisms of AVM formation and provide new drug targets

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 Marianne Clancy MPA

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Goal 1: Promote Human Health

Global cohorts to fill gaps in knowledge trending idea

Given the global burden of disease, what does NHLBI plan to do to establish a diverse global cohort to connect basic sciences to population health, in a way that differences in phenotypes around the world can be studied rapidly? For example, why not start by supporting a coalition of cohorts originally funded by the Global Heart Initiative?

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 big challenge is for global proposals to get through regular RO1 mechanisms, as the study sections tend to be US-centric. Issuing special RFAs for US institutions to collaborate with global partners and setting special study sections will help.

Feasibility and challenges of addressing this CQ or CC

This should be feasible

Name of idea submitter and other team members who worked on this idea K.M. Venkat Narayan

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-8 net votes
5 up votes
13 down votes
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Goal 2: Reduce Human Disease

Molecular basis for cardiac and neurological damage after cardiac arrest

What is the sequence and time course of molecular events that cause irreversible cardiovascular and neurologic dysfunction during and after cardiac arrest?

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 AHA Staff & Volunteers

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-4 net votes
1 up votes
5 down votes
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