Goal 3: Advance Translational Research

Leveraging PEPFAR infrastructure for CVDs

How do we go about leveraging existing infrastructure, such as PEPFAR, to reduce the risk of HLBS diseases among HIV patients and other vulnerable populations? • Common goals and deliverables between NHLBI and partners will need to be identified • The best return on investment of NHLBI funds will need to be determined • Feasible T4 translation interventions in PEPFAR funded studies utilizing HIV populations with HLBS ...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 :

• Decrease the burden of heart, lung, blood, and sleep diseases in studies funded by PEPFAR in HIV populations

• Lessons learned could be expanded to HIV populations outside of Africa

• T4 translation interventions in these populations could help reduce risk factors for heart, lung, blood, and sleep diseases leading to better health outcomes

Feasibility and challenges of addressing this CQ or CC :

• PEPFAR has identified and recruited existing HIV populations in Africa which can be leveraged by NHLBI for heart, lung, blood, and sleep chronic disease research

• Infrastructure that has received PEPFAR investments can also be leveraged to undertake T4 translation interventions

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

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-1 net votes
7 up votes
8 down votes
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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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1 net vote
1 up votes
0 down votes
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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 »

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

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

Non-Adherence of Patients with Chronic Respiratory Diseases

There are various reasons responsible for patients’ non-adherence. One of them is insufficient or lack of education about medications and equipment required for their treatment.

Submitted by (@vlady.rozenbaum)

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

Details on the impact of addressing this CQ or CC :

There is a critical need to develop uniform guidelines and handouts addressing the confusion over the proper use of medications (particularly inhalers) and equipment (i.e. oxygen). Improper use leads to diminished or no benefit, frustration, and, ultimately, even to a patient's decision to stop the treatment.

Feasibility and challenges of addressing this CQ or CC :

This is an issue that has been universally acknowledged for a number of years. With the help of patient focus groups, convened at the NHLBI, national pulmonological conferences, or at local venues around the country, appropriate materials can be created to benefit patients and reduce a huge burden on nation's economy due to decreased productivity and increase in hospital admissions.

Name of idea submitter and other team members who worked on this idea : COPD-ALERT

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0 net votes
20 up votes
20 down votes
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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

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11 net votes
15 up votes
4 down votes
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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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Goal 3: Advance Translational Research

Animal models of vascular diseases

How can we better model human vascular disease in all its complexity?

­This is key to more effective translation of both diagnostics and therapeutics. Develop improved animal models of vascular diseases including PAD, aneurysm, venous diseases, to facilitate fundamental research and preclinical development.

Submitted by (@societyforvascularsurgery)

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 : Society for Vascular Surgery

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2 net votes
3 up votes
1 down votes
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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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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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Goal 3: Advance Translational Research

Multicenter trials of therapies for rare diseases.

Infrastructure for performing research in rare diseases should be enhanced to allow efficient accrual to multicenter trials.

Submitted by (@marymh)

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

Details on the impact of addressing this CQ or CC :

Many of the malignant and non-malignant blood diseases that fall under the purview of the NHLBI are uncommon though, in aggregate, important contributors to the burden of disease in the US population. Although in some areas, like blood and marrow transplantation (BMT), there exists an infrastructure for multicenter trials, in many areas there does not. This makes testing potentially effective therapies very difficult. The large increase in the number of national BMT trials following the implementation of that network indicates the effectiveness of the approach, which could be expanded to include cellular therapies and other novel approaches.

Feasibility and challenges of addressing this CQ or CC :

The current R01 process does not lend itself to efficient and rapid implementation of trials to test new approaches or to the time needed to complete trials that focus on long-term survival and quality of life endpoints. Even within the existing transplant network, efficiencies could be gained by infrastructural enhancements like a common IRB or government-assisted contracting (i.e., CRADAs), a streamlined process for protocol review (e.g. a one- versus two-step process), etc. Additionally, enhanced ability to collaborate with other organizations or institutes, without undue bureaucratic burden, would allow better use of NIH funds so that more trials could be done.

Name of idea submitter and other team members who worked on this idea : Mary Horowitz

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80 net votes
114 up votes
34 down votes
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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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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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