Goal 2: Reduce Human Disease

Fetal basis for Adult Disease

Maternal exposures during pregnancy have the potential to alter development and lead to lifelong susceptibility to disease. There is epidemiological evidence of this in the asthma field, where maternal smoking leads to increased asthma rates. However, the molecular mechanisms by which maternal exposures cause lung disease later in life are not known and the influence of in utero exposures on susceptibility to lung cancer, ...more »

Submitted by (@dc0000)

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 the impact of maternal exposures on fetal lung disease would make a major impact on human health by giving regulatory agencies the data they need to make educated decisions with respect to issues such as nicotine regulation, air pollution, water pollution, and other sources of maternal exposures.

Feasibility and challenges of addressing this CQ or CC :

With the established animal and stem cell models of development, this research is immediately feasible.

Name of idea submitter and other team members who worked on this idea : Diane Carlisle

Voting

10 net votes
17 up votes
7 down votes
Active

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

Voting

10 net votes
21 up votes
11 down votes
Active

Goal 1: Promote Human Health

Lung Development Reactivation

What stimuli cause developmental processes to be reactivated in the lung?

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

Voting

5 net votes
13 up votes
8 down votes
Active

Goal 2: Reduce Human Disease

Role of vascular development in pulmonary hypertension

Does interrupted or aberrant pulmonary vascular development contribute to pulmonary hypertension?

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

Voting

16 net votes
28 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 3: Advance Translational Research

Genome Profiling

What structural changes need to be implemented in the health-care community in order to support the use of genomic information in clinical trials and drug development for hematologic diseases?

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

Details on the impact of addressing this CQ or CC :

In various blood disorders, including hematologic malignancies, there are both inherited and somatic genetic alterations that contribute to predisposition, transformation, disease progression, responsiveness to therapy, and treatment complications. The presence of such genetic alterations underscore the need for the identification of rare but traceable mutations as well as the integration of such genomic information into clinical trials. By implementing a few structural changes in the healthcare sector, a clinical trial infrastructure can be established that accounts for proper application of sequencing technology. Some examples include the creation of genome diagnostic networks that address accrual of sufficient patients, procurement of suitable tumor/non-tumor material for sequencing, as well as pharmacodynamic and correlative biology studies in hematologic diseases.

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

Voting

11 net votes
22 up votes
11 down votes
Active

Goal 4: Develop Workforce and Resources

Career Development in "Group Based" Science

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:

 

NHLBI should be challenged on how best to provide career development grants to junior faculty involved in “group based” clinical and bench science.

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

Voting

7 net votes
26 up votes
19 down votes
Active

Goal 3: Advance Translational Research

Rx for HFpEF

HLBI should make it a priority to develop therapeutic options for the treatment of heart failure with preserved ejection fraction.

Submitted by (@johnrobinson)

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

Details on the impact of addressing this CQ or CC :

Heart failure with reduced ejection fraction (HFrEF), formerly called systolic heart failure, is the classical form of heart failure that is characterized by defective ventricular contraction. The most common variant of heart failure is heart failure with preserved ejection fraction (HFpEF), formerly called diastolic heart failure, characterized by resistance to ventricular filling. The prevalence of HFpEF has been rising steadily over the past two decades at a rate of increase of 1% per year, while the prevalence of HFrEF which has remained stationary. The most common causes of HFpEF are ischemia, obesity, hypertension, diabetes and ageing. Since the population is increasingly obese, hypertensive, diabetic and ageing, the incidence of HFpEF will be the dominant heart failure phenotype over the next decade. The clinical management of HFpEF is complicated by lack of therapeutic options that provide survival benefit. Therapies of proven benefit in HFrEF have repeatedly been shown to add little if any benefit in HFpEF. The prognosis of HFpEF is about the same as HFrEF, with 5-year mortality ranging from 54% to 65%.

Feasibility and challenges of addressing this CQ or CC :

Recent developments in our understanding of the molecular mechanisms of myofilament regulation and assays can be used to develop lead compounds for treating HFpEF.

Name of idea submitter and other team members who worked on this idea : John Robinson

Voting

1 net vote
13 up votes
12 down votes
Active

Goal 2: Reduce Human Disease

Signaling in AVM Developmoent

BMP9 circulates in the blood and signals through the endothelial cell. IN the absence of Alk 1, such as in HHT, the vessels become over-active. The overactivity can be partially balanced by activation of a second signaling pathway: notch. Would targeting notch be a useful drug target to reverse AVM formation

Submitted by (@mariannes.clancy)

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 : Marianne Clancy MPA, Chris Hughes PhD

Voting

1 net vote
1 up votes
0 down votes
Active

Goal 1: Promote Human Health

Intersecting Developmental Biology with Vascular Physiology and Biology

Although many think of the vasculature as a lump sum of vessels that all react in a similar fashion to a certain stimulus, e.g., alpha-adrenergic activation, this is not the situation. For example, coronary resistance vessels show little to no direct response to alpha-adrenergic activation while resistance vessels in most organs show marked constriction. Another example is the response of different vessels to angioplasty ...more »

Submitted by (@wchilian)

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 challenge facing many specialists in vascular medicine, vascular surgery, and cardiology is understanding the ramifications, and the basis, of the vascular pathology in the context of the organ system. Another way of re-stating this as a question is: Are the unique attributes of the vascular biology, pathology and physiology of a particular organ system connected to specific aspects of development. This question would help both the basic on clinical scientists understand the basis of why a blood vessel in the kidney may be different than one in the heart, or in the brain with the goal of devising more selective therapies to approach vascular disease in specific organs. Scientists in the area of vascular development have long appreciated that vascular cells in different organs arise from different embryological origins; yet how this information translates into the intricacies of vascular control, or responses to pathology is not resolved. Understanding the basic biological mechanisms of how the embryological source of the vasculature affects pathology and physiology could engender treatment of vascular disorders.

Feasibility and challenges of addressing this CQ or CC :

This idea could be implemented by encouraging multi-PI efforts from vascular developmental biologists, and investigators engaged in studies of microvascular control mechanisms and/or vascular biologists interested in vascular pathologies such as restenosis and vascular lesions. Advances in fate mapping techniques have enabled developmental biologists to track embryological origins of cells into specific organ systems into adulthood. With such a multi-faceted approach a better understanding of vascular physiology and pathophysiology will be obtained that hopefully will be translated into more effective treatments.

Name of idea submitter and other team members who worked on this idea : William M. Chilian

Voting

15 net votes
26 up votes
11 down votes
Active

Goal 3: Advance Translational Research

Incentivizing Earlier Investment in NHLBI-Funded Technologies

How might NHLBI assist its awardees to attract private sector funding or partnerships earlier in the product development process to help bridge the gap between academic discoveries and product commercialization?

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 :

Attracting private sector support earlier in the development pipeline would help fill an important funding gap between academic discoveries and product commercialization, enabling products to reach patients more quickly, and improving the return on NHLBI’s investments in basic research.

Feasibility and challenges of addressing this CQ or CC :

Some existing initiatives such as the SBIR Phase IIB Bridge and Small Market Awards encourage non-federal investors to invest earlier in NHLBI-funded technologies. In addition, the NCAI is designed to support critical feasibility studies and business case development to de-risk earlier investment by the private sector. These efforts are showing early signs of success, but impact only a small proportion of NHLBI-funded basic research discoveries.

Estimates for the cost of developing a new drug or device range from the hundreds of millions to billions of dollars and 10-15 years to get from the lab to the patient. The NHLBI cannot fully support that development, so private sector support is critical for biomedical technologies to be commercialized. Overall private capital investment in the life sciences is increasing, but it is not being targeted at heart, lung, blood, and sleep technologies or at the seed stage of development. Venture capital investment in heart, lung, blood, and sleep technologies has declined or remained stagnant since 2008 (http://graphics.wsj.com/venture-capital-and-the-human-body/) and seed stage investment from the private sector for early stage high-risk projects is in short supply (PWC Moneytree: https://www.pwcmoneytree.com/HistoricTrends/CustomQueryHistoricTrend).

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

Voting

15 net votes
23 up votes
8 down votes
Active

Goal 3: Advance Translational Research

Animal Models for Translational Research and Drug Development

There is a need to identify and develop suitable animal models (e.g. larger, non-primate animal models) that faithfully predict the outcomes of new medicines and treatments in heart, lung, blood, and sleep (HLBS) disorders prior to human clinical trials.

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 :

If animal models can faithfully predict the outcomes in human clinical trials of new medicines and treatments, it will reduce the economic burden for the failure of drug development.

Feasibility and challenges of addressing this CQ or CC :

Identification of current available animal models;

Development of new animal models with recent advances in mammalian genome projects and gene targeting technologies could be done over the next 5-10 years

Medical research, especially in basic discovery, has benefited significantly from the use of various animal models, such as gene-targeted and transgenic mouse models. However, many discoveries from animal models (e.g. mouse models) failed to translate into human applications.

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

Voting

73 net votes
92 up votes
19 down votes
Active