Goal 3: Advance Translational Research

psychosocial care in sickle cell disease

What are the most effective trans-disciplinary and multi-level strategies for accelerating psychosocial care with sickle cell disease and how psychosocial factors impact families?

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

Details on the impact of addressing this CQ or CC

Since sickle cell has multiple layers in medical treatment strategies, how can the same thought process happen when it comes to psychosocial matters? How can the NHLBI develop effective patient engagement trans-disciplinary and multi-level strategies that work with medical strategies to deal with psychosocial matters for individuals and families?

Name of idea submitter and other team members who worked on this idea Sickle Cell Warriors, Inc community members

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Goal 3: Advance Translational Research

Implementation Science to Improve Care in Sickle Cell Disease

There are approximately 100,000 individuals living with sickle cell disease in the US, however study after study has shown that many lack access to the few existing evidence based interventions such as hydroxyurea. We need to investigate novel ways to increase acess to hematology care and disease modifying therapies.

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

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12 net votes
14 up votes
2 down votes
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Goal 3: Advance Translational Research

Screening the work force for genetic arrhythmias

Is anyone in your family at risk for a potentially lethal genetic arrhythmia? 4000 young people die each year because they bear a genetic mutation that makes them susceptible to a sudden fatal arrhythmia. The symptoms are easy to identify and awareness of these symptoms would help unsuspecting families.

 

It is estimated that one of these syndromes (LQTS) is 3 times more common in the US than childhood leukemia.

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 are 3 simple warning signs for families bearing dominant mutations that could lead to arrhythmia and sudden death. These are unexplained fainting or seizure during exercise or startle, an unexplained sudden death of a young family member, chest pain and/or shortness of breath during exercise. A simple questionnaire of all families with children entering school or any athlete signing up for a sport, or any adult entering the work force would help identify potential family members at risk for these genetic arrythmias.

Feasibility and challenges of addressing this CQ or CC

A simple questionnaire of all families with children entering school or any athlete signing up for a sport, or any adult entering the work force would help identify potential family members at risk for these genetic arrythmias. Such potential patients could then be further screening by a EKG and a consult with a cardiologist.

Name of idea submitter and other team members who worked on this idea Andy Golden

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Goal 2: Reduce Human Disease

Stem Cell Immunology

We now can create critical cell types like cardiomyocytes etc. from stem cells. Additionally, we are learning the rules of using these cells to rebuild tissues. A major gap in our knowledge relates to the immunobiology of these cells. Lessons from transplantation medicine are only partially applicable, because solid organs are more complex and likely more immunogenic than defined cell populations.

How does the immune... more »

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

Details on the impact of addressing this CQ or CC

We now can generate large quantities of critical cell types whose deficiencies underlie many chronic diseases like heart failure. This breakthrough brings us to the next-level impediment: the immune system. While induced pluripotent stem cells have the potential to obviate rejection, in practical terms this is cost-prohibitive: It will cost huge amounts of money to produce and qualify a single patient's cell dose. Moreover, human cardiomyocytes are potent when given to infarcted hearts in the acute or sub-acute phase of infarction, but they have no benefit with chronic heart failure. The 6 months required to produce iPSC-cardiomyocytes precludes their autologous use for myocardial infarction.

We need an off the shelf cell therapy product for myocardial infarction that can be mass produced and qualified for large numbers of patients. This means an allogeneic product is necessary. Identifying the immune response to cardiomyocytes or other cell products will teach us how to precisely immunosuppress the patient, thereby minimizing complications, or alternatively, how to engineer the cells so as to avoid immunogenicity in the first place.

Lessons from the study of cardiomyocyte transplantation could extend to dopamine neurons, pancreatic beta-cells, retinal cells, myelinating cells and many other areas that cause common chronic disease.

Feasibility and challenges of addressing this CQ or CC

We know a great deal of transplant immunology from hematopoietic stem cell transplantation (graft versus host) and from solid organ transplantation (host versus graft). There are good mouse and large animal (including non-human primate) models of stem cell differentiation and organ transplantation. This offers low hanging fruit where, in perhaps 5 years, we could discern the critical similarities and differences between transplanting stem cell derivatives and organ or marrow transplantation. These studies will inform clinical trials of allogeneic human stem cell derivatives that will be underway by then.

Success in this area will require bringing together researchers interested in stem cell biology and transplant immunology. A properly resourced RFA from NIH could be just the thing needed to promote this interaction.

Name of idea submitter and other team members who worked on this idea Charles Murry, MD, PhD

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23 net votes
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22 down votes
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Goal 3: Advance Translational Research

Application of data science to extract information from EHR/EMR

There is a need to utilize bioinformatics to analyze electronic health records / electronic medical records (EHR/EMR) documentation of practice-based pulmonary and sleep medicine to better understand longitudinal care delivery patterns and outcomes, identify changes in evidence, inform practice, and foster reverse translation to integrate basic and clinical research.

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

Details on the impact of addressing this CQ or CC

Utilizing HER/EMR for research can decrease the cost and improve the generalizability of clinical research.

Feasibility and challenges of addressing this CQ or CC

The feasibility of extracting health information from EHR/EMR has been tested and validated by many NIH supported grants, especially the National Centers for Biomedical Computing program.
The effort of extracting health information from EHR/EMR has been supported for many years by NIH’s initiatives such as National Centers for Biomedical Computing and BD2K to create tools for utilizing HER/EMR, and now it is time for domain experts to test, validate, improve these tools on the EHR/EMR in their specific fields.

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

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54 net votes
81 up votes
27 down votes
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Goal 3: Advance Translational Research

Modulating Immune Checkpoints to Enhance Curative Potential of Autologous Transplantation in classical Hodgkin lymphoma (cHL)

PD-L1 and PD-L2, engage PD-1 receptors on activated T cells and induce T-cell exhaustion. Antibody-mediated PD-1 blockade has already been successfully exploited as a therapeutic strategy in solid tumors. PD-L1 is expressed on suppressor immune cells in the tumor microenvironment and in cHL tumors. PD1 blockade has shown clinical activity in cHL. Disease relapse, post autoHCT; however remains the most common cause of... more »

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

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26 net votes
46 up votes
20 down votes
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Goal 3: Advance Translational Research

Development of integrated research teams

There needs to be development of integrated research teams that include clinicians, scientists, engineers, etc.

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 Research Advocacy Committee, American Thoracic Society

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1 up votes
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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?

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

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10 net votes
15 up votes
5 down votes
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Goal 4: Develop Workforce and Resources

Reproducibility Initiatives in Heart, Lung and Blood Research

Scientists feel tremendous pressure to publish numerous scientific papers in order to receive NIH funding and tenure at academic institutions. Cognitive biases of scientists and publication biases of journals that publish this barrage of papers will likely result in the publication of findings that are probably not reproducible (see "Why Most Published Research Findings Are False" by John P. A. Ioannidis in PLOS Medicine... more »

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

Details on the impact of addressing this CQ or CC

By distinguishing research findings which are reproducible from those which aren't, researchers will be able to build future research programs on solid scientific foundations.

There are many reasons for why research may not be reproducible, ranging from simple biological variations (cells from one supplier may behave differently than cells from a different supplier) to conscious/unconscious biases or misconduct. No matter what the underlying cause is, irreproducible research findings that are not recognized as such will result in a tremendous waste of time and resources. Graduate students or postdoctoral trainees may waste entire years of their precious training period conducting experiments that are based on published papers which may turn out to be irreproducible.

NHLBI could significantly improve the quality of research by building an infrastructure that supports the assessment of reproducibility and widely shares these findings.

Feasibility and challenges of addressing this CQ or CC

One of the challenges for assessing reproducibility of published work is that it is considered not very innovative and there is no funding available. NIH grants are awarded to highly innovative proposals which venture into new territories and not proposals which want to confirm the validity of published work. However, the returns of investing into reproducibility testing might be enormous because irreproducible results would be identified and weeded out, thus preventing loss of resources and time.

The NHLBI could develop funding mechanisms specifically designed to support research proposals that will test the reproducibility of high impact findings that have not yet been independently verified. The study sections would review these proposals using novel criteria designed for such studies. The emphasis of the study section review would lie on questions such as "Is this an important enough question that it merits reproducibility testing?" instead of the traditional "Is this a cutting-edge technology that nobody has previously used?"

Challenges would include identifying journals that would published results of these studies and agreeing on what constitutes reproducibility (i.e. is it enough if the major conclusion or effect is reproduced even though the effect size may be very different?).

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

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2 net votes
5 up votes
3 down votes
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Goal 2: Reduce Human Disease

The Use of Therapeutic Apheresis to Reduce Circulating Levels of Galectin-3 and other Cancer and Inflammation Promoting Factors

Inflammation plays roles in cancer initiation, promotion, and progression. Elevated circulating galectin-3 (Gal-3) protein and other cancer and inflammation promoting factors (CIPFs) such as C-reactive protein and VEGF are associated with tumorigenesis and may play causative roles. Plasma Gal-3 is a biomarker, prognosticator, and pathogenic mediator of diverse cancers and is emerging as a therapeutic target. Preliminary... more »

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

Details on the impact of addressing this CQ or CC

Apheresis therapy in a clinical setting, both alone and in combination with conventional protocols, shows great potential to enhance treatment regimens, reduce dosage and side effects, improve drug deliver to target tissues, reduce long term treatment related morbidity and improve outcomes with significant benefits for patients with a broad range of cancer types and stages.

Feasibility and challenges of addressing this CQ or CC

The need for well designed, randomized clinical trials would be readily feasible with the appropriate IND. Grant support will be needed for further development of this concept, as well as to develop columns with more optimized and specific capabilities, in addition to clinical trials demonstrating efficacy.

Apheresis is highly underutilized and underfunded in the US, while Apheresis research and development is much more advanced and widely utilized in Europe and Asia.

Name of idea submitter and other team members who worked on this idea Isaac Eliaz, MD

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33 net votes
40 up votes
7 down votes
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Goal 2: Reduce Human Disease

Interactions between anticoagulant therapy and antiretroviral drugs

Cardiovascular pathology has become a major problem in the management of the HIV-infected patient during the ART era. A large number of HIV patients will receive anticoagulants drugs for secondary prevention of cardiovascular disease. It is therefore critical to understand the interactions between antiretroviral therapy and anticoagulant therapy to safely treat HIV patients.

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

Details on the impact of addressing this CQ or CC

With over 50% of HIV-infected patients in the US anticipated to be > 50 years of age by 2015, the overall risk of CVD will be significantly higher and could become the main challenge for the management of chronic HIV infection. A large number of HIV-infected patients with CVD will therefore need treatment for primary and secondary prevention of atherothrombotic events. The secondary prevention of CVD almost invariably includes prescription of one or multiple anticoagulants drugs. It is therefore conceivable that anticoagulant therapies will be frequently associated with ART for the management of HIV patients, which already developed CVD. The interactions between these therapies are not well studied and are critical for the management of the HIV-infected patients.

Feasibility and challenges of addressing this CQ or CC

Feasibility: 1) retrospective studies on a large number of HIV patients that had cardiovascular events and were treated with antiretroviral drugs; 2) prospective studies comparing different antiretroviral regimens associated with the most current anticoagulant therapy recommended for secondary prevention of CV disease; 3) use of animal models of AIDS for testing new anticoagulants and the interaction with the antiretroviral drugs.

Name of idea submitter and other team members who worked on this idea Ivona Pandrea

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2 net votes
5 up votes
3 down votes
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Goal 1: Promote Human Health

What motivates adults to exercise?

Getting people to change from a sedentary to active lifestyle is difficult. What institutional supports are most effective? What is the cost benefit of prevention versus treating cardiovascular disease.

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

Details on the impact of addressing this CQ or CC

Reducing the costs of treating cardiovascular disease (and possibly some cancers)

Feasibility and challenges of addressing this CQ or CC

Considering the money spent on treatment this strategy should be feasible.

Name of idea submitter and other team members who worked on this idea Shoshana

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21 net votes
39 up votes
18 down votes
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Goal 3: Advance Translational Research

Implementation of T4 Translation Research Platforms and Networks

How can cost-effective implementation of late stage translation (T4) research protocols be facilitated for heart, lung, blood, sleep diseases and health inequities?

Can research platforms and networks be created and utilized to facilitate execution of multi-level interventions and approaches for the end user in collaboration with key stake holders?

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

Details on the impact of addressing this CQ or CC

Answering this question would lead to timely implementation and dissemination of new knowledge that will be available to address the current heart, lung, blood, sleep health burden.
One of NHLBI’s current strategic plan’s goals is to translate research knowledge for use in populations so that it has significant positive health impacts and provides a return on investment from discovery and early translation research. Currently, only a fraction of new knowledge yielded from proven effective early stage translation research is being used in the real world – resulting in an avoidable disease burden. Late stage translation (T4) research studies the implementation of proven-effective interventions at a multi-level to include populations, communities, healthcare systems, providers, families and patients. Conducting T4 research requires development of comprehensive research teams across communities, public health and health care delivery systems, families, and patients along with unique translation T4 research methods and metrics. Because resource intensive infrastructure is needed to conduct high quality T4 research and this infrastructure is not widely or readily available, a platforms and network for conducting protocols will prove efficient and provide high quality standard outputs.

Feasibility and challenges of addressing this CQ or CC

The NHLBI Health Inequities Think Tank highly recommended that creating T4 translation research platforms and networks would meet the needs of the scientific community enabling them to respond to the heart, lung, blood, sleep health burden.

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

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4 net votes
13 up votes
9 down votes
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Goal 2: Reduce Human Disease

How can we control environmental risks (smoking, obesity, activity levels)?

How can we control environmental risks (smoking, obesity, activity levels)?

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 topic of primary prevention has received considerable discussion by President Obama and others. We certainly support research into vaccinations, tobacco cessation, clean air and other measures to prevent lung disease. In addition, we would like to broaden the discussion to secondary prevention. For example, chronic obstructive pulmonary disease (COPD) affects roughly 10% of people over age 40 years with its victims commonly succumbing to cardiovascular disease and cancer. Although clearly cardiovascular disease and cancer are important topics, we advocate for further research into the underlying lung disease. Similarly, people with sleep apnea are at risk of cardiometabolic complications, but currently more effort is placed on managing the complications than the underlying cause.

Name of idea submitter and other team members who worked on this idea Research Advocacy Committee, American Thoracic Society

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3 up votes
0 down votes
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