Goal 2: Reduce Human Disease

Blood specific diseases due to defects in ubiquitous pathways

Why are some blood diseases called by genetic mutations in ubiquitous pathways. Diamond Blackfan anemia is due to a mutation in ribosomal proteins.

Submitted by (@zon000)

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 number of blood diseases are due to signaling defects in ubiquitous pathways. Why would a ribosomal protein mutation lead to a red blood cell specific disorder. Certain anemias or myelodysplastic syndromes are due to mutations in chromatic factors. The chromatin factor defects can lead to clonal hematopoiesis.

Feasibility and challenges of addressing this CQ or CC :

A large scale centralized effort could select projects on blood specific diseases due to defects in ubiquitous pathways. A correlation of gene expression, translation, or transcription could lead to a better understanding of responses of blood cells to the stress of defects in common pathways.

Name of idea submitter and other team members who worked on this idea : Leonard Zon

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2 net votes
9 up votes
7 down votes
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Goal 2: Reduce Human Disease

Genetic and Molecular Tools for Drug Allergy - Hypersensitivity

As the current chair of the Research and Training Division, I would like to convey that the AAAAI membership would like the NHLBI to consider the following in the development of its strategic plan: Given that more patients are treated with newer and better targeted medications including chemotherapy, monoclonal antibodies, small molecules and others that have increased the number of hypersensitivity reactions, which ...more »

Submitted by (@wheeze)

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 : Mitchell Grayson on behalf of the American Academy of Allergy, Asthma, and Immunology

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-4 net votes
10 up votes
14 down votes
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Goal 2: Reduce Human Disease

Improving the phenotyping of the major (chronic) heart, lung, and blood diseases

Which phenotypic and molecular characteristics predict differential responses to therapy in individuals with chronic heart, lung, blood, and sleep (HLBS) 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 :

• Enable pathophysiologically targeted therapies and prevention

• Enable subgroup assessment of intervention

• Better define gene-gene and gene-environment interactions

• Improve risk stratification

• Understand those who are protected against disease

• Inform development of better in vitro and in vivo models to assess disease and response

Feasibility and challenges of addressing this CQ or CC :

Advances in –omics, diagnostics, cell biology, imaging are ready to be applied

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

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30 net votes
42 up votes
12 down votes
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Goal 3: Advance Translational Research

Translating cardiac development/genetics knowledge into therapy

What is needed to translate our knowledge of cardiac development and congenital heart disease genetics into novel diagnostic and/or therapeutic strategies for congenital or acquired heart disease?

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 :

Develop new therapies for congenital or acquired heart disease.

Feasibility and challenges of addressing this CQ or CC :

We are poised to take advantage of the incredible advances in our understanding of cardiac development and genetics which have resulted from the development of high throughput technologies.

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 1: Promote Human Health

Cardiac Gene Networks

What is the level of intra-tissue variation of cardiac development gene regulatory networks at single cell resolution?

Submitted by (@nhlbiforumadministrator)

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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2 net votes
16 up votes
14 down votes
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Goal 2: Reduce Human Disease

High risk individual’s apparent protection from disease

Can we define the basis for high risk individual’s apparent protection from disease?

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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-7 net votes
8 up votes
15 down votes
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Goal 2: Reduce Human Disease

Genetic variants of complex diseases in Asian American Subgroups

What are the genetic variants influencing complex heart, lung, blood, and sleep traits and diseases in Asian American subgroups?

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 :

High impact, given that in the U.S.: a) Asian Americans are the fastest growing racial/ethnic group, and b) heart diseases and chronic lower respiratory diseases are the second and fourth leading causes of death, respectively, among Asian Americans

Feasibility and challenges of addressing this CQ or CC :

Genetic and genomic technologies are currently available for such a study.

Although there is a growing number of genetic studies in Asian countries such as China, the research findings are not necessarily generalizable to Asian Americans, who differ in various ‘exposure variables’ including diet, behaviors, and environment. Furthermore, there is a need to conduct research among Asian American subgroups (see list immediately below) rather than lumping them into a single category, given the heterogeneity across subgroups. Sufficient sample sizes are needed to provide reliable estimates of gene-by-environment interactions; however, Asian Americans are often underrepresented in research studies in the U.S. Asian American subgroups, in order of highest to lowest % in the U.S.: Chinese; South Asians (ancestry from Indian subcontinent), Filipino, Vietnamese, Korean, and Japanese.

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

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

Understanding the Genetic & Epigenetic Basis of Congenital Heart Disease?

Over the last thirty years, our fundamental understanding of the genetics and pathogenesis of congenital heart disease has lagged the tremendous advances in the surgical and clinical care of infants with this group of disorders. We need to close this gap with investigation into the genetic basis of congenital heart malformations to develop new models of disease. The goall is translate an improved molecular genetic and ...more »

Submitted by (@jamesr.priestmd)

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

Details on the impact of addressing this CQ or CC :

Congenital heart disease (CHD) is the most common congenital malformation and the most common cause of mortality during the first year of life. Approximately 70% of cases occur sporadically without a strong family history or identifiable genetic syndrome, and the primary heritable basis of most non-syndromic CHD has yet to be identified. Studies of affected kindreds, syndromic disease, and more recently genome wide association studies (GWAS) have shed light on a handful of causal loci, while exome sequencing and studies of structural variation uncovering rare de novo variants in trios have yielded only an 8-10% rate of diagnosis in cohorts with CHD. Despite the application of contemporary techniques and study design to genetic discovery in CHD, the majority of the genetic risk for human cardiac malformations remains unexplained.

Feasibility and challenges of addressing this CQ or CC :

One key challenge is that many of the stakeholders including those affected with congenital heart disease (children), along with the physicians make a diagnosis and referral (obstetricians, neonatologists, general pediatricians), are generally funded by other agencies (NICHD). Trans-agency collaboration and cooperation is necessary to improve the translational research structures necessary to improve disease.

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22 net votes
37 up votes
15 down votes
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Goal 2: Reduce Human Disease

Does lowering circulating lipoprotein(a) levels influence cardiovascular outcomes?

A comprehensive research strategy and plan is needed to determine the most efficient, safe, cost-effective and widely applicable strategy to decrease circulating levels of lipoprotein(a) and to determine whether lowering circulating lipoprotein(a) levels will reduce the risk of developing cardiovascular disease such as a heart attack or a stroke as well as the progression of atherosclerosis or aortic stenosis.

Submitted by (@serevill)

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

Details on the impact of addressing this CQ or CC :

Approximately 20% of the population are characterized by elevated circulating levels of lipoprotein(a), regardless of age, gender or blood cholesterol levels. Estimates suggest that up to 90% of the variation in plasma lipoprotein(a) levels could be due to genetic factors, which makes lipoprotein(a) the most prevalent inherited risk factor for cardiovascular diseases (CVD). Large-scale genetic studies have shown that Lipoprotein(a) was the strongest genetic determinant of CVD such as atherosclerosis and aortic stenosis. Lipoprotein(a) is one of the strongest predictors of residual CVD risk and has been shown to improve CVD risk prediction in several population-based studies. Lipoprotein(a) is also one of the strongest known risk factors for spontaneous ischemic stroke in childhood.

A comprehensive research strategy aiming at identifying, evaluating interaction with other risk factors, treating and educating patients with elevated lipoprotein(a) levels would result in substantial reductions of health care costs in the US and around the globe by reducing the burden of CVD while simultaneously improving the quality of life of these patients.

Feasibility and challenges of addressing this CQ or CC :

The list of pharmaceutical agents that reduce lipoprotein(a) levels is steadily increasing. There are approximately half a dozen strategies that have been shown to significantly and safely lower lipoprotein(a) levels. One of the challenges of this research strategy will be to determine which of these strategies represent the most efficient, safe, cost-effective and widely applicable approach to lower lipoprotein(a) levels and CVD outcomes.

Increasing awareness on lipoprotein(a) and CVD will also be of utmost importance for this effort as relatively few physicians perform lipoprotein(a) testing and even fewer patients are aware of their lipoprotein(a) level. The first sign of high lipoprotein(a) is often a heart attack or stroke. Our challenge will be to identify patients with high lipoprotein(a) that could be enrolled in trials of risk characterization and lipoprotein(a)-lowering.

Name of idea submitter and other team members who worked on this idea : Sandra Revill Tremulis on behalf of the Lipoprotein(a) Foundation Scientific Advisory Board

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235 net votes
297 up votes
62 down votes
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Goal 2: Reduce Human Disease

Assessing gene knockout humans more effectively

What insights can be gathered from patients with single gene functional mutations to improve our understanding of the pathobiology of human disease?

Submitted by (@nhlbiforumadministrator)

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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-9 net votes
5 up votes
14 down votes
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Goal 3: Advance Translational Research

Drug Hypersensitivity Databases

As the current chair of the Research and Training Division, I would like to convey that the AAAAI membership would like the NHLBI to consider the following in the development of its strategic plan: Drug Hypersensitivity is a growing concern for patients who are unprotected against potentially severe and lethal reactions. It would be important to generate databases to characterized the different drug reactions, their ...more »

Submitted by (@wheeze)

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 : Mitchell Grayson on behalf of the American Academy of Allergy, Asthma, and Immunology

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-7 net votes
11 up votes
18 down votes
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Goal 1: Promote Human Health

Identify genetic variants of sleep/circadian disorders

Most aspects of variation in sleep and circadian rhythm are heritable. Moreover, all common sleep disorders aggregate in families. The response to sleep loss is also a highly heritable trait. Identifying gene variants for these disorders will elaborate new molecular pathways that could be targets for future interventions.

Submitted by (@jnoel0)

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 critical challenge would have the following impact. First, the information could be used to help identify these different disorders, including potentially subtypes. Addressing this challenge will lead to identification of new molecular pathways to disease. This will stimulate future research on their role and mechanisms of pathogenesis. Moreover, these pathways may be open to new drug interventions and hence new therapies for disease.

Feasibility and challenges of addressing this CQ or CC :

There is a growing number of cohorts both in the United States and internationally that have sleep phenotype data and DNA. These could be the basis of genetic studies.

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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84 net votes
117 up votes
33 down votes
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