Goal 1: Promote Human Health

Emerging importance of RNA regulation

What are the roles of RNAs (e.g., microRNAs, long non-coding RNAs, etc.) in myocardial growth, adaptation, and injury healing response?

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 :

As an example, recent studies suggest key regulatory roles of RNAs (e.g., microRNAs and long non-coding RNAs) in cardiac pathological hypertrophy and heart failure. Better understanding of such mechanisms will spur development of new therapies based on these mechanisms.

Feasibility and challenges of addressing this CQ or CC :

Most of the infrastructure and methods are in place. There appears to be growing interest and excitement about the potential of this research area. However, this field needs more researchers.

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

Voting

4 net votes
18 up votes
14 down votes
Active

Goal 1: Promote Human Health

The Human Virome and Host Interactions in Heart, Lung, and Blood

What are the unknown elements of the human virome, and what host-virome interactions affect the heart, lung, and blood health and diseases? A major challenge has been the need for in vitro culture systems and animal models for studying the virome, which is a significant limitation that has forced current studies of the virome to be mostly descriptive. NHLBI has supported one research group to identify human virome and ...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 :

• The virome contains the most abundant and fastest mutating genetic elements on Earth. The human virome is constituted of viruses that infect host cells, virus-derived elements in our chromosomes, and viruses that infect the broad array of other types of organisms that inhabit us. The virome may influence the host in profound ways independent of classical viral disease. The immune system is continuously stimulated by chronic systemic viruses and this aspect of host-microbiome interactions appears specific to the virome. The virome is considered one of the drivers of idiopathic systemic inflammation that has been linked to many of the most severe public health threats, including cardiovascular diseases. Disruptions in immunity by immunosuppressing events can undoubtedly alter the interactions of the virome with the host. However, little research has been done in all of these aspects other than limited descriptive studies to identify the presence or composition of the human virome. The NHLBI Microbiome Working Group in June 2014 clearly identified under-representation of studies of the human virome. Identification and characterization of unknown viral elements of the human virome and research on the interactions with the host will allow exploration of their impact on heart, lung and blood health and diseases, including impact in the presence of immunosuppression with the host such as in AIDS or HIV infection.

Feasibility and challenges of addressing this CQ or CC :

This initiative is feasible because of new technologies that have been developed recently such as the deep sequencing techniques. The initiative is also timely in that research supported by the NIH Human Microbiome Program and other programs has allowed us to better understand microbiome, especially bacteria in and on humans, and we began to realize the magnitude of the virome. This initiative will attract more investigators to not only identify more elements of the virome but more importantly to understand the roles of the human virome in heart, lung and blood health and diseases, and eventually to help develop diagnostic and intervention strategies.

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

Voting

13 net votes
29 up votes
16 down votes
Active

Goal 1: Promote Human Health

Re-examining Antigenicity of Rare Blood Disease Proteins

What specific roles do protein glycosylation and protein complex formation on stable and activated cellular membranes play in inherent immunogenicity and antibody formation to life-saving therapies for rare blood disorders?

 

NHLBI leadership and collaboration with NIAID is needed to bring this combined expertise to bear on the understanding and prevention of this most significant complication of hemophilia therapy.

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 :

Inhibitory alloantibody formation to critical life-saving therapies impedes effective replacement therapy in up to 30-40% of children and adults with congenital blood diseases, thereby significantly increasing the complications of the underlying disease. For children with hemophilia A, this treatment complication has significantly limited the impact of the last 20 years of therapeutic advances in product efficacy and safety. Discovery science in this area has focused on the relationship between the immune response and treatment circumstances, and the epitope specificity of the targeted immune response. However, this scientific pathway to discovery has not yielded the critical mechanistic data required to inform effective prevention strategies. Recent advances in our understanding of the co-factors for immunogenicity, the biochemistry of coagulation factor complex formation on cellular membranes, glycobiology and gene transfer must now converge to create a potential platform for exploring new paradigms of immunogenicity, and thus leading to new strategies for inducing tolerance to future new therapeutics in hemophilia.

Feasibility and challenges of addressing this CQ or CC :

A recent workshop sponsored by the National Hemophilia Foundation highlighted the threat to novel therapies for hemophilia as well as curative gene therapy from the unsolved problem of replacement protein or gene product antigenicity. However recent advances in our understanding of the co-factors for immunogenicity, the biochemistry of coagulation factor complex formation on cellular membranes, glycobiology and gene transfer, can now converge to create a potential platform for exploring new paradigms of immunogenicity, and thus leading to new strategies for inducing tolerance to future new therapeutics.

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

Voting

-1 net votes
8 up votes
9 down votes
Active

Goal 1: Promote Human Health

Gene regulatory networks in HLB disease mechanisms

What is the level of population variation of gene regulatory networks in heart, lung, and blood and sleep disease mechanisms? Can we use different animal model strains to identify key factors in networks and modifier genes?

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 :

Improve our understanding of the pathophysiology of disease and perhaps identify novel targets for intervention.

Feasibility and challenges of addressing this CQ or CC :

Advances in high throughput technology have made addressing these questions possible.

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

Voting

10 net votes
22 up votes
12 down votes
Active

Goal 1: Promote Human Health

Human normal variation and resilience across lifespan

What is the measureable normal human variation at the -omic, cellular, organ, and system levels within the population and across the lifespan? • What are the range of normal human cellular functions that create resilience at all levels—cells, organs, organ systems? • What inter-organ, tissue, and cellular communications maintain individual health and the health of populations? • How do we understand why individuals with ...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 :

• Will provide a better definition of what is normal in order to better interpret and exploit the big data available through increased personalized monitoring and use of EMRs.

• Insights into the underlying mechanisms of resilient phenotypes will provide new paradigms for disease prevention and treatment.

Feasibility and challenges of addressing this CQ or CC :

Feasibility will depend on the level of investment (large) and accessibility to commons data.

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

Voting

19 net votes
26 up votes
7 down votes
Active

Goal 1: Promote Human Health

Host and environmental factors effect on transplantation biology and regenerative medicine

How does inflammation and cell injury induce the immune system during transplant rejection? How do we control immune responses to enable cell- and tissue-regenerative strategies? • How does inflammation and cell injury induce the immune system during transplant rejection? • How do we control immune responses to enable cell and tissue regenerative strategies? • How do we use iPS cell based and gene editing based therapies ...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 :

Treatment of human diseases

Feasibility and challenges of addressing this CQ or CC :

Facilitated by progress in genome editing, stem cell biology, immunology

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

Voting

34 net votes
48 up votes
14 down votes
Active

Goal 1: Promote Human Health

Trans-kingdom regulation of HLBS systems

What is the interplay of the micro- and macroenvironment and their effect on gene and protein expression and overall effect on phenotypes in HLBS systems?

 

Need for unbiased approaches for information capture. Technologies for capturing real time, dynamic and contextual information

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 :

Increase and gain novel understanding of heart, lung, and blood physiologic systems

Feasibility and challenges of addressing this CQ or CC :

Emerging technologies, databases and merging of disciplines in the context of big data has the potential to make this feasible in the next 5-10 years

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

Voting

-6 net votes
3 up votes
9 down votes
Active

Goal 1: Promote Human Health

Control of the molecular and cellular characteristics of regional variations in the lung

What are the regional variations in cellular and molecular characteristics (from epigenetics to microbiome) in the lung, and what controls these variations?

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 :

Advance in this research will help to understand the heterogeneity of lung disease

Feasibility and challenges of addressing this CQ or CC :

Novel technologies, e.g. single cell analysis and imaging have been developed to get high resolution characterization of the cells in the lung.

Many lung diseases are heterogeneous with regional variations, which are not fully characterized at the molecular and cellular level. Mechanisms underlying the formation of the regional variations are also poorly understood.

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

Voting

0 net votes
12 up votes
12 down votes
Active

Goal 1: Promote Human Health

Critical Windows in Early Development to Maximize Lung Health

Is there a critical window of growth and development for maximizing lung function?

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 :

Low lung function during childhood tracks to early adulthood and contributes to early onset disease. Lung health promotion is needed, but we know little about what can enhance and protect human health during rapid phases of lung development in utero and growth postnatally to adulthood.

Feasibility and challenges of addressing this CQ or CC :

Researchers could turn their attention on healthy and “maximally” health populations (human and model organisms) to understand genetic and environmental exposures that influence lung function at upper ends of the spectrum (>2 SD from the mean).

Recent findings suggest that there is an urban-rural continuum of lung function in specific ethnic groups; and interventions with maternal dietary supplements can enhance lung function in offspring. These set the stage for further study on developing knowledge of early life events that can inform lung health promotion.

Voting

5 net votes
17 up votes
12 down votes
Active

Goal 1: Promote Human Health

Stem cell niche in the lung

How do lung progenitors recognize stem cell niches, and what cell-cell interactions mediate normal repair?

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 :

Research on the stem cell-niche interaction will enhance our understanding of stem cell behavior, enable manipulation of stem cell activity and differentiation potential, and facilitate the development of stem cell-based therapy.

Feasibility and challenges of addressing this CQ or CC :

Developing novel models for in vitro 3D culture and in vivo transplantation assays will facilitate the progress.

 

Recent advances have identified and characterized several lung progenitor cell types. However research gaps remain on understanding the interaction of stem cells with the niche, and how the microenvironment impacts on the stem cell activity during injury/repair.

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

Voting

8 net votes
23 up votes
15 down votes
Active

Goal 1: Promote Human Health

Environmental stimuli and the lung: predictors of homeostatic or pathological responses

What are the molecular and cellular responses in the lung that occur after environmental stimuli that predict homeostatic resilience or transition to disease, disorder, or aging?

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 :

Addressing this line of research could define biomarkers and pathways useful for prediction of how human response to an external stimulus of varied nature (i.e. microorganism, chemical, physical) could lead to specific outcomes in relationship to the duration of the exposure and the genetic makeup of the individual exposed. Identification of early signals and the pathways involved could lead to novel preventative or therapeutic approaches.

Feasibility and challenges of addressing this CQ or CC :

Methods for systems biology approaches to address complex pathobiological iterations are ready to be exploited to answer these questions.

Great progress has been made in the clarification of basic mechanisms of molecular and cellular response to environmental stimuli, in cross-sectional analyses. The continuum of the response in relationship to the genetic background of individuals responding with a homeostatic or pathological long-term outcome is missing from these data.

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

Voting

10 net votes
15 up votes
5 down votes
Active

Goal 1: Promote Human Health

Mapping the Vasculome

What is the best method to develop an integrated map of the expression patterns of the vasculature (RNA, protein, and epigenome) within each organ system?

 

Sampling standards and quality control are major outstanding issues.

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 :

The vasculome is comprised of a vast network of vessels that globally interacts with all of the other organ systems within the body. Disorders of the vasculature have a significant adverse effect on those organ systems and are a major source of mortality and morbidity. Systematic mapping of vasculome expression will reveal disease causality patterns that have thus far been unobserved.

Feasibility and challenges of addressing this CQ or CC :

The tools are available, the coordination is not. The NHLBI and VBHB have the expertise, the experience, and the leadership necessary to oversee the multiple studies, date collections, and organizational systems needed for mapping the vasculome.

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

Voting

3 net votes
12 up votes
9 down votes
Active