Strategic Goal: Goal 3: Advance Translational Research

Identification of autoantigens that elicit pathogenic immune responses in cardiovascular diseases

Pathogenic immune responses participate in the pathogenesis of many cardiovascular diseases. However, the autoantigens and foreign antigens that elicit the pathogenic immune responses have been poorly identified. Currently, the regulatory mechanisms on immune responses associated with diseases got some attentions. But, without detailed characterizations of this wide spectrum of autoantigens and foreign antigens in patients ...more »

Submitted by (@xfyang)

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

Feasibility and challenges of addressing this CQ or CC :

1) use peptide/protein based microarray to antibody autoimmune responses associated with each major cardiovascular diseases;

2) use MHC tetra-mers or similar techniques to characterize T cell autoimmune responses associated with each major cardiovascular diseases;

3) determine autoantigen repertoire changes in patients' responses to current therapies, especially therapies with immune modulating effects;

4) develop autoantigens-based immune therapies for clinical trials

Name of idea submitter and other team members who worked on this idea : Professor Xiaofeng Yang, MD, PhD, Professor Hong Wang, MD, PhD, Professor Klaus Ley, MD

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Strategic Goal: 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

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7 net votes
14 up votes
7 down votes
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Strategic Goal: Goal 1: Promote Human Health

Role of the lymphatic system in heart, lung, blood, sleep health and diseases

What is the role of lymphatic system in normal function of the heart? Do dysfunctional lymphatics contribute to heart failure? Do lymphatics have a role in recovery after MI? It has been reported that lymphatic vasculature transport HDL during reverse cholesterol transfer. Do lymphatics have a role in atherosclerosis? What is the contribution of lymphatic system to asthma or COPD? Does the lymphatic system contribute ...more »

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 :

Understanding how lymphatic system contributes to normal physiology of heart, lung, blood, sleep systems will help also lead to new approaches for treatment of heart, lung, blood, sleep diseases.

Feasibility and challenges of addressing this CQ or CC :

Basic understanding of the development and hemodynamics of the lymphatic system and reagents to study the lymphatic function are available.

Lymphatic vasculature is essential for fluid hemostasis in the body, collects and returns the protein- and lipid-rich interstitial fluid to blood circulation, and also involved in immune cell trafficking and inflammation. Given these important physiological roles, function of the lymphatic system is expected to contribute to normal physiology of organs and its dysfunction to major diseases. There is very little or no information how the lymphatic system contribute to health and diseases of the cardiovascular, pulmonary and blood systems, and there are many unanswered questions. Answers to these questions may lead to new approaches for treatment of major HLB diseases. Main challenge is to get heart, lung, blood, sleep investigators interested in studying the contribution of the lymphatic system to heart, lung, blood, sleep health and diseases.

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

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50 net votes
77 up votes
27 down votes
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Strategic Goal: Goal 3: Advance Translational Research

Treating cardiovascular disease in persons with mental health disorders

How can we most effectively prevent and treat cardiovascular disease among persons with serious mental disorders?

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 :

Clinical anxiety disorders affects 40 million people in the US and the lifetime prevalence of PTSD is 6-8%,. The incidence of PTSD in particular is rapidly expanding in the US; this condition doubles the risk of a cardiac event.

 

The prevalence rates are higher in some populations; 3 out of 10 US military veterans have a diagnosis of PTSD, and many more are undiagnosed. Among patients at a VA, a diagnosis of PTSD increased the probability of circulatory problems (odds ratio 3.7). In another study, every additional PTSD symptom increased the risk of developing cardiovascular disease by 17%. Thus, the impact of developing more effective treatments adapted to the needs of this vulnerable population could be significant.

Feasibility and challenges of addressing this CQ or CC :

As the incidence of many mental health disorders such as PTSD and depression increases, the need for developing and adapting treatments for this population becomes critical.

 

Effective treatments may not be optimal for persons with serious mental illnesses and strategies to tailor treatments to the challenges of this vulnerable population are needed.

Individuals with mental illnesses such as major depressive disorder, bipolar disorder, and anxiety disorders are at significantly higher risk for cardiovascular disease than are those without these illnesses. Those with serious mental illnesses die an average of 25 years earlier, frequently from cardiovascular disease. The incidence of PTSD is rapidly expanding in the US; this condition doubles the risk of cardiovascular events.

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

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19 net votes
30 up votes
11 down votes
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Strategic Goal: Goal 3: Advance Translational Research

In-Vitro Assays to Predict Clinical Response

How can NHLBI support studies that produce in-vitro assays to predict clinical response and ways to translate those results into patient therapies through novel clinical trials, including those for small patient populations and rare diseases?

Submitted by (@skrenrich)

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 : Cystic Fibrosis Foundation

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3 net votes
6 up votes
3 down votes
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Strategic Goal: Goal 1: Promote Human Health

Epigenetics and Genomics

There is a need to investigate hemoglobin biosynthesis in order to develop novel approaches to treat sickle cell disease, thalassemia, and other anemias.

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

Details on the impact of addressing this CQ or CC :

Studies on epigenetic mechanisms have extraordinary promise for the development of transformative therapeutic approaches for non-malignant hematologic disorders, however, limited progress has been made in advancing therapies to counteract the often crippling complications of these conditions. In the case of sickle cell disease, an ensemble of proteins has been implicated in mediating the epigenetic repression of gamma-globin expression, raising the possibility that antagonizing the actions of these proteins to increase gamma-globin expression may be a useful treatment strategy. However, in certain cases, some of these proteins are deemed “undruggable,” based on their structural attributes. There is a critical need to identify druggable components of the multi-step epigenetic mechanisms as well as develop better models and assays that will more effectively identify modulators of “undruggable” proteins. Given the rich proteome and improved technologies available today, studies of proteomics, metabolomics, and regulatory RNAs are likely to reveal promising translational avenues. In addition, approaches to modifying the expression of the components of this pathway are underway using developing gene therapy strategies, such as viral vectors and/or gene editing can quickly advance therapy in sickle cell disease and β-thalassmia.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology (ASH)

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42 net votes
62 up votes
20 down votes
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Strategic Goal: Goal 2: Reduce Human Disease

Stem Cell Biology

There is a need to develop an artificial and functional hematopoietic stem cell (HSC) niche that allows for the expansion of repopulating HSCs.

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

Details on the impact of addressing this CQ or CC :

Methods to expand hematopoietic stem cells have continued to be examined extensively because stem cell numbers in the graft are important for clinical outcomes following transplantation. These numbers are particularly relevant in umbilical cord blood (UCB) transplantation, where low numbers of stem cells are directly related to delayed hematopoietic and immune reconstitution. Improved HSC expansion strategies may significantly impact transplantation outcome, enabling broader applications beyond UCB transplantation. Furthermore, these strategies are also needed to realize the full therapeutic potential of genome editing technologies to correct hematopoietic stem cells derived from patients with hematologic disorders. Since efforts to expand HSCs in cytokine-supported liquid cultures have been largely unsuccessful, efficient expansion will require an appropriate context that is provided by the hematopoietic stem cell niche. Future studies must also evaluate how niche signals regulate stem cell function to optimize cell expansion, and proper humanized mouse models must be developed to help predict stem cell function and regulation by the niche.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology (ASH)

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28 net votes
46 up votes
18 down votes
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Strategic Goal: Goal 2: Reduce Human Disease

Lack of Collaboration Across NIH Institutes

There are many significant questions in CVD prevention that cross the disciplines represented by the different institutes. For example, the obesity epidemic, poor nutrition, and physical inactivity are relevant to CVD, neurological disease, diabetes, and cancer. Tobacco use is directly relevant to cancer and CVD. Social determinants and disparities affect multiple diseases and outcomes. Reducing obesity will require interventions ...more »

Submitted by (@stephen.fortmann)

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

Details on the impact of addressing this CQ or CC :

Two or more collaborating NIH Institutes could afford to fund creative projects that neither institute can afford alone.

Feasibility and challenges of addressing this CQ or CC :

NIH Institutes have a long history of isolation from one another. This has undoubtedly suppressed creativity and interdisciplinary research. It is inherently bureaucratic and reflects poorly on science. As an outsider I can only speculate about how to address this issue, but it would be well worth some attention at the highest levels.

Name of idea submitter and other team members who worked on this idea : Stephen P. Fortmann

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6 net votes
7 up votes
1 down votes
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Strategic Goal: 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?

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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8 up votes
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Strategic Goal: Goal 1: Promote Human Health

Extreme makeover: harnessing adaptation mechanisms for therapy

What extreme adaptive physiological mechanisms in heart, lung, and blood systems might have the greatest potential to be targeted or employed in therapeutic strategies? Human physiology, including the heart, lung and blood systems, is known to possess extreme adaptive mechanisms to counter extreme conditions or unusual situations. Although some studies are being done, many of these mechanisms have not been fully explored ...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 :

May lead to new therapeutic strategies for HLB diseases. May improve our understanding of HLB physiology and adaptation.

Feasibility and challenges of addressing this CQ or CC :

It is feasible to ask specific questions about adaptation mechanisms under extreme conditions and develop experiments to test them. This can be done in various experimental models as well as in humans.

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

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12 down votes
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Strategic Goal: Goal 2: Reduce Human Disease

How can the study of rare diseases inform our understanding of common diseases?

How can the study of rare diseases inform our understanding of common diseases?

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 : Research Advocacy Committee, American Thoracic Society

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Strategic Goal: Goal 3: Advance Translational Research

Genome Profiling

There is a need to facilitate the integration of genomic and epigenomic profiling into drug discovery efforts by using genomic methods to sequence and analyze blood disease subtypes.

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

Details on the impact of addressing this CQ or CC :

Despite the important information that has been generated from sequencing studies in various blood disorders, for many hematologic disease subtypes, the limited scope of sequencing and the insufficient number of cases sequenced has prevented researchers from gaining truly useful insights. Whole-genome sequencing of large numbers of samples, with an emphasis on poorly studied and rare entities, is required to fully define the landscape of genetic changes underlying the development of blood diseases. Further, genetic and epigenetic alterations that drive hematologic diseases and the extent to which normal cells are distinct from malignant cells needs to be more broadly elucidated since many blood diseases, including hematopoietic cancers, disturb epigenetic regulators. The knowledge gained from understanding these processes and integrating genomic and epigenomic profiles could provide additional precision medicine opportunities and guide drug discovery efforts.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology

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0 net votes
16 up votes
16 down votes
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