Goal 4: Develop Workforce and Resources

Training Biomedical Research Experts for Life Beyond the Ivory Tower

Only 10-20% of graduates from PhD programs in the biomedical sciences will pursue a scientific career in the traditional tenure track academic model. This is in part due to a mismatch between a large number of highly qualified scientists and the relatively small number of tenure track positions available. Instead of viewing the careers of the 80-90% as "alternative careers", we have to accept that in fact the traditional ...more »

Submitted by (@jalees)

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 majority of trainees in NHLBI graduate and postdoctoral training programs will likely pursue a diverse spectrum of careers such as scientists in the biotech and pharmaceutical industry, educators, health and science journalists, editors, patent lawyers or health/science consultants in the world of finance and politics.

 

Most NHLBI T32 training grants are awarded to academic institutions and the mentors tend to be tenure-track or tenured academics with NIH R01 funding. The question we have to address is whether these traditional training programs and mentors are well-suited to advise and prepare trainees for careers outside of academia.

 

The NHLBI should fund novel training programs that require or encourage involving mentors outside of academia and funding training projects that allow trainees to work in industry, publishing, writing, politics, non-profits and other non-traditional areas related to heart, lung and blood research. This will prepare trainees for future careers and increase their likelihood of obtaining satisfying jobs.

Feasibility and challenges of addressing this CQ or CC :

Such newer T32 training programs will require a rethinking of the goals of training. There will be challenges for how to assess the quality and identify benchmarks of success for the training programs. Instead of merely looking at the number of publications by a trainee, one should also consider the impact they will make on society by using their expertise in biomedical research to improve education, health and science reporting, political and financial decisions, etc.

 

One should also consider awarding such training programs jointly to multiple institutions and encourage sharing of trainees. For example, a T32 program that wants to train future science writers and journalists with expertise in cardiovascular medicine would encourage their trainees to visit multiple partner institutions with expertise in cardiovascular medicine and in journalism/writing during their training period.

 

Instead of spending two years in one lab under a single mentor working on one or two projects, non-traditional T32 programs would encourage exposure to multiple projects, mentors, etc.

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

Voting

0 net votes
4 up votes
4 down votes
Active

Goal 2: Reduce Human Disease

Cardiometabolic Disease Risks Associated with Sleep Deficiency

How does insufficient sleep duration, irregular timed sleep schedules, and poor sleep quality contribute to the pathophysiology of lung, heart and blood diseases?

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 :

Sleep deficiency and untreated sleep disorders threaten the health of 20-30 percent of US adults through an increased risk of stroke, hypertension, diabetes, inflammatory disease, and all-cause mortality. Developing the scientific evidence-base of validated interventions will enhance the management of cardiometabolic and pulmonary risks to health, present new opportunities for secondary prevention, and reduce associated burden on health care systems.

Feasibility and challenges of addressing this CQ or CC :

Improving sleep health through informed public recognition of decision-relevant science, and relatively low cost therapies for management of sleep disorders are available for immediate assessment of impact in appropriate clinical trials to demonstrate efficacy and effectiveness.

Discovery research advances implicate an array of cellular sleep and circadian mechanisms in pathophysiological pathways leading to cardiometabolic and pulmonary disease.

 

Irregular and disturbed sleep impairs cellular biological rhythm in all tissues and organs leading to oxidative stress, unfolded protein responses, and impaired cell function. The pathophysiological findings juxtaposed with epidemiological evidence of disease risk indicate that sleep deficiency contributes to an erosion of health across the lifespan over and above the effects of aging.

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

Voting

94 net votes
122 up votes
28 down votes
Active

Goal 3: Advance Translational Research

Enhancing Cardiovascular Health in Childhood Through Adulthood

To enhance or maintain ideal cardiovascular health (CVH) in children and adolescents, what novel and long-term interventions can be implemented using multi-level (i.e., targeting individual, family, community, and built environment) and sustainable approaches?

Would implementation and translation of the AHA 2020 impact goals in children and adolescents enhance their CVH through adulthood?

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 :

Broad impact on the health of children and adolescents and ultimately, the health of the nation.

Feasibility and challenges of addressing this CQ or CC :

Because there are some proven modalities in small-scale studies for improving cardiovascular health in children. Most are short-term or tested mostly in adults. This CQ focuses on trials that could span 10 years from Childhood into adulthood.

NHLBI has supported numerous large-scale trials (e.g., Girls health Enrichment Multisite Studies-GEMS, PATHWAYS, Child and Adolescent Trials for Cardiovascular Health-CATCH, Trial of Activity in Adolescent Girls-TAAG, and other investigated interventions in children and adolescents along with NICHD and other ICs) that could be harnessed to support this initiative.). NHLBI is supporting multi-level trials such as the Childhood Obesity Prevention and Treatment Research (COPTR) Consortium) that could provide modalities to enhance CVH in youth. Currently, there are no long-term trials spanning childhood through young adulthood in the US on this topic. An example of such a study is The Special Turku Coronary Risk Factor Intervention Project for Children [STRIP] study in Finland. Pahkala et al., Circulation. 2013;127:2088-2096.

 

A major challenge is cost, retention in trial and long-term adherence to intervention modalities. These could be mitigated using public-private funds (cost), incentives and/or clinical trial methodologies to enhance participation and adherence. Ability to motivate children and adolescents throughout their growth could be a challenge.

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

Voting

17 net votes
34 up votes
17 down votes
Active

Goal 1: Promote Human Health

Transformative Impact of Proteomics

The proteomics field has dramatically progressed over the past 20 years, with advancements and improvements in experimental designs and sample preparation protocols, as well as mass spectrometry equipment, approaches, and analysis. This has resulted in substantial forward progress towards a proteomic pipeline to establish cause and effect mechanisms of cardiovascular disease. There is a need for CV proteomics that resolve ...more »

Submitted by (@mllindsey)

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 necessary tools have been assembled, and managing implementation will reduce the time required for completion of larger scale projects.

Feasibility and challenges of addressing this CQ or CC :

high feasibility; the challenge will be managing communication across groups to maximize impact

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

Voting

196 net votes
234 up votes
38 down votes
Active

Goal 2: Reduce Human Disease

Development of non-contrast alternatives in cardiac magnetic resonance imaging

Critical Challenge

Submitted by (@str0001)

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

Details on the impact of addressing this CQ or CC :

Late gadolinium-enhancement cardiac magnetic resonance imaging (MR) plays a crucial role in the evaluation of patients with suspected myocardial scar tissue. Alternative methods to contrast-enhanced MR however are in need, given the number of patients who have concomitant compromised renal function and concern for nephrogenic systemic fibrosis. Noncontrast MR techniques such as diffusion-weighted imaging would complement and eventually replace gadolinium administration thus impacting the evaluation of those with suspected and confirmed infiltrative cardiac processes and systemic diseases.

Feasibility and challenges of addressing this CQ or CC :

Late gadolinium enhancement technique characterizes enhancement patterns of heart disease, identifies areas amenable to ablation, and aids in decisions pertaining to workup and therapy. The underlying mechanism of Brownian motion/diffusion in the expanded extracellular space makes diffusion weighted imaging a potential gadolinium-saving modality. Diffusion MR, applied primarily in the brain and abdominal imaging, is underutilized in the heart given respiratory and cardiac motion. A need exists to further develop and apply noncontrast MR techniques towards cardiovascular applications. Such methods are promising noncontrast alternatives to characterize patients with myocardial disease, determine those with differing prognoses, and direct appropriate therapies to subgroups.

Name of idea submitter and other team members who worked on this idea : Society of Thoracic Radiology

Voting

3 net votes
6 up votes
3 down votes
Active

Goal 2: Reduce Human Disease

RCT of stepped-care depression treatment on CV events & death

Does treating depression improve survival and reduce major adverse cardiac events in acute coronary syndrome patients?

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 :

A substantial evidence base now exists showing that depression is associated with a two-fold increased risk of death and recurrent CV events in cardiac patients, leading to a recent AHA scientific statement recommending its elevation to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome (Lichtman et al., 2014). Yet there is currently no clinical trial evidence that reducing depression improves cardiac morbidity and mortality. A clinical trial, using new, more effective depression treatment methods, such as collaborative care approaches that combine psychological counseling with medication in stepped-care fashion, is needed to determine whether effective treatment of depression can improve survival and reduce clinical cardiovascular events in cardiac patients.

Feasibility and challenges of addressing this CQ or CC :

Newer stepped-care treatments for depression, combining medication and psychotherapy, have recently been developed and found to more effectively reduce depression than earlier treatments. By using these newer treatment methods to substantially lower depression, we can better answer the question as to whether treating the newly acknowledged risk factor of depression in ACS patients can improve clinical outcomes in these patients.

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

Voting

5 net votes
22 up votes
17 down votes
Active

Goal 2: Reduce Human Disease

Relevance of cardiovascular disease associated with autoimmunity research

NIH estimates up to 23.5 million Americans suffer from autoimmune disease (AD) and up to 24 million from heart diseases. As a result, NIH and AHA estimates the annual direct health care costs for AD to be in the range of $100 billion and $200 billion for heart and stroke diseases. Yet this area of research has been neglected and underfunded. The proposition is for NHLBI to partner with other NIH institutes dealing with ...more »

Submitted by (@mboutjdir)

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

Details on the impact of addressing this CQ or CC :

Reduce the impact of autoimmune diseases on the heart and vascular system.

Feasibility and challenges of addressing this CQ or CC :

Generate RFAs dedicated to the field of autoimmune associated cardiovascular diseases.

Name of idea submitter and other team members who worked on this idea : M. Boutjdir

Voting

11 net votes
15 up votes
4 down votes
Active

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 »

Submitted by (@hcai00)

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

Voting

27 net votes
30 up votes
3 down votes
Active

Goal 3: Advance Translational Research

Develop biomarker panel to predict CVD risk in -omics era

There is a need to utilize the vast data generated in -omics research to develop biomarker panels for better prediction of cardiovascular disease (CVD) risks. •Cardiovascular diseases develop over decades and different panels of markers may be required for different stages •Lead molecules as potential biomarkers need to be selected by a panel of experts •Standard procedures about sample preparation, data acquisition, ...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 :

•Develop specific and sensitive markers for early prevention with more predictive power. Biomarkers that can detect specific perturbations in the system, such as metabolic status and vascular integrity prior to the occurrence of the diseases can be used for early preventive treatment of cardiovascular diseases.

 

•Identify vulnerable population who cannot be identified by the current LDL-HDL profiling

 

•Allow for more personalized treatment

Feasibility and challenges of addressing this CQ or CC :

•An increase in system biology studies using –omic approaches have provided huge data to mine through and find potential biomarkers, such as microRNA, DNA, lipids, proteins, and other metabolites, which can be used to assess changes proceeding cardiovascular diseases occurrence.

 

•The NIH-wide Big Data to Knowledge (BD2K) initiative launched in 2012 may have laid out some framework.

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

Voting

7 net votes
14 up votes
7 down votes
Active

Goal 2: Reduce Human Disease

Understanding the Role of the Vasculature in Dementia

Dementia is traditionally grouped into vascular dementia, Alzheimer's dementia, Parkinson's dementia and other causes of dementia. Vascular dementia is generally thought to be a consequence of strokes but there are some recent studies indicating that even Alzheimer's dementia may have a vascular underpinning. Vascular permeability is increased in the early stages of Alzheimer's disease and it is possible that similar ...more »

Submitted by (@jalees)

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 NHLBI could fund programs which enable vascular biologists to collaborate with neuroscientists and neurologists in order to understand whether the vasculature has a causal role in the progression of dementia.

 

 

 

Can interventions that improve vascular function prevent the progression of dementia? Instead of using broad interventions such as statins which affect numerous signaling pathways, vascular biologists could target selected aspects of vascular health such as improving vascular barrier function and vascular regeneration.

 

If these interventions that have been shown to be efficacious in other vascular beds outside of the brain are also effective in the brain, then important new therapies could be developed for dementia which is likely to become one of the leading cause of death in the next decades.

Feasibility and challenges of addressing this CQ or CC :

A key challenge for targeting the brain vasculature will be the blood-brain barrier. Understanding the role of the blood-brain barrier in dementia will be a prerequisite to developing novel vasculature-directed therapies.

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

Voting

9 net votes
13 up votes
4 down votes
Active

Goal 2: Reduce Human Disease

Imaging indicators of metabolic syndrome and cardiopulmonary disease

Critical Challenge

Submitted by (@str0001)

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

Details on the impact of addressing this CQ or CC :

Obesity and metabolic syndrome affect a large portion of the population and affects multiple organ systems. Identifying obesity phenotypes by imaging will impact the significant healthcare issue presented by MetS and could provide a reliable, non-invasive index of disease severity, guide prevention and intervention response.

Feasibility and challenges of addressing this CQ or CC :

Metabolic syndrome, abnormal metabolism, may be potentially linked to obesity and cardiopulmonary disease. Theories exist but are in need of clarification. The relationship between metabolic syndrome and multiple other diseases including chronic obstructive lung disease, coronary atherosclerosis, and obesity warrants further investigation and can be elucidated through imaging. Advances in computed tomography (CT) and magnetic resonance imaging (MR) enable assessment of the cardiopulmonary manifestations, with promising MR techniques to complement high-resolution imaging data achievable with chest CT and coronary CT angiography. Assessment of CT and MR techniques in combination with three-dimensional quantitative analysis of manifestations of metabolic syndrome such as fat deposits derived from different adipocytes (white fat versus brown fat) such as in the subcutaneous, visceral, epicardial, and perivascular regions is feasible with current technology and may enable differentiation of those with varying risks of cardiovascular and pulmonary disease. The association of imaging parameters, metabolic syndrome, and associated diseases are in need of investigation, and knowledge gained may prove crucial for identifying those at risk for metabolic syndrome and at higher risk for complications in the large population of our country affected by obesity.

Name of idea submitter and other team members who worked on this idea : Society of Thoracic Radiology

Voting

6 net votes
10 up votes
4 down votes
Active

Goal 3: Advance Translational Research

Regenerative Medicine 2.0 in Heart and Lung Research - Back to the Drawing Board

Stem cell therapies have been quite successful in hematologic disease but the outcomes of clinical studies using stem cells for cardiopulmonary disease have been rather modest. Explanations for this discrepancy such as the fact that our blood has a high rate of physiologic, endogenous turnover and regeneration whereas these processes occur at far lower rates in the heart and lung. Furthermore, hematopoietic stem cells ...more »

Submitted by (@jalees)

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

Details on the impact of addressing this CQ or CC :

Some barriers to successfully implementing cardiopulmonary regeneration include the complex heterogeneous nature of the heart and lung.

 

Hematopoietic stem cells can give rise to all hematopoietic cells but the heart and lung appear to contain numerous pools of distinct regenerative stem and progenitor cells, many of which only regenerate a limited cell type in the respective organ. The approach of injecting one stem cell type that worked so well for hematopoietic stem cells is unlikely to work in the heart and lung.

 

We therefore need new approaches which combine multiple regenerative cell types and pathways in order to successfully repair and regenerate heart and lung tissues. These cell types will likely also require specific matrix cues since there are numerous, heterogeneous microenvironments in the heart and lung.

 

If we rethink our current approaches to regenerating the heart and lung and we use combined approaches in which multiple cell types and microevironments are concomitantly regenerated (ideally by large scale collaborations between laboratories), we are much more likely to achieve success.

 

This will represent a departure from the often practiced "Hey, let us inject our favorite cell" approach that worked so well in hematologic disease but these novel, combined approaches targeting multiple endogenous and/or exogenous regenerative cells could fundamentally change our ability to treat heart and lung disease.

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

Voting

7 net votes
11 up votes
4 down votes
Active