Goal 3: Advance Translational Research

Translational Bioinformatics Spanning Multiple Scales of Biologic Complexity to Implement Precision Pulmonary Medicine at the Po

What translational bioinformatics tools could be used in pulmonary medicine to allow multidimensional, multi-scale modeling of clinical and biomolecular data to assist clinical decision-making?

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 :

Deployment of bioinformatics tools to construct multi-dimensional, multi-scale models of pulmonary (mal)functioning from large heterogeneous data sets spanning biological molecules, subcellular compartments, signaling pathways, cells, tissues, organs, organ systems and clinical therapeutics trials to predict actionable precision medicine for clinicians at the point of pulmonary care.

Feasibility and challenges of addressing this CQ or CC :

A variety of existing powerful informatics methods for integrating a vast wealth of clinical and high-dimensional data across DNA to organism compartments to develop multi-scale modeling approaches to improve point-of-care precision medicine. Consistent with a continuous learning healthcare system, precision medicine modeling is recursive, tentative pending better understanding and therefore continuously learning.

Fundamental to implementation of precision medicine is the ability to extract heterogeneous data from basic and clinical research to be integrated systematically into clinical practice in a cohesive and large-scale manner. Deployment of precision medicine models to predict (mal)functioning progression and response the treatment in daily practice relies strongly on the availability of an efficient bioinformatics platform that assists in the translation of basic and clinical science knowledge.

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

Voting

-2 net votes
10 up votes
12 down votes
Active

Goal 2: Reduce Human Disease

Study on key product factors for optimal Bone Marrow Transplantation (BMT) graft function

Hematopoietic progenitor cells (HPC) collected by Apheresis is the most common source used for BMT. How the cells are collected and what kinds of cells are collected can affect BMT graft function. Limited studies have been done to study the key product factors in relationship to optimal graft function. Questions remain such as the optimal lymphocytes contents for reduced infection post BMT, optimal megakaryocyte precursor ...more »

Submitted by (@yanyunw)

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

Details on the impact of addressing this CQ or CC :

Optimal cell therapy products can lead to reduced post BMT complication and reduced morbidity and mortality.

Feasibility and challenges of addressing this CQ or CC :

In vitro, animal studies, clinical samples can be used for key product factors for optimal BMT graft function.

These can be achieved if funding is available, as there are many centers perform allo and auto BMT.

Funding support is critically needed in this area.

Name of idea submitter and other team members who worked on this idea : Yanyun Wu on behalf of ASFA

Voting

70 net votes
93 up votes
23 down votes
Active

Goal 3: Advance Translational Research

A Collaboration Market Place for Industry and Academia to advance Translational Medicine

There is a vast amount of data regarding specific gene and protein targets, especially in the post genomics era with many well validated targets, and even more "strong candidates". Drug companies have libraries of compounds that could be good inhibitors/enhancers for these new targets but lack an internal program, IP of the target, or a sufficiently large market to initiate risky and expensive drug screens, let alone ...more »

Submitted by (@ims000)

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

Details on the impact of addressing this CQ or CC :

An NHLBI sponsored and funded "Market Place" could be set up to partner drug companies seeking funds to perform earlier phase screens with academic investigators seeking funds to learn more about their protein target or advance a therapy. NHLBI could fund a successfully paired collaboration up to 100% of the cost, with a sliding scale of matched-costs from the industrial partner based on their market capitalization (e.g. big Pharma at 100%, Medium Pharma at 50%, and early-stage Pharma at 0%)

 

Well thought-out global contractual agreements for "non-disclosure" and "IP sharing", beneficial to both parties before and after initial 'pairing' of a collaboration, would significantly enhance the speed and feasibility of the studies.

 

More compounds could be tested for more targets, addressing rarer conditions, or common conditions where only a small proportion of the affected cases are impacted by mutations or deficiency of the target proteins.

 

Drug companies would be incentivized to examine more targets without necessarily needing a large market for a future drug.

 

Later stage studies – pre-clinical, Phase 1, and Phase 2 – could then be re-championed at the Market Place for additional NHLBI funding, either with new partners or the same partners to further advance successful compounds.

Feasibility and challenges of addressing this CQ or CC :

Contractual negotiations between Industry and Academia/Clinicians is a significant barrier to Translational Medicine and personalized medicine in particular.

 

Often ideas are not shared simply due to a lack of non-disclosure agreements in place. A Market-place to share ideas behind a well-structured “non-disclosure” firewall at the NHLBI website would facilitate the speed of discussion and stimulate collaboration.

 

Funding within industry can be limited by board and share-holder goals. There is typically little incentive to advance translational programs at early stages with no or limited medium or long-term financial benefits. Providing funding to facilitate and perform these research collaborations would incentivize Pharma to collaborate with academics who may hold IP or data on novel targets discovered with NHLBI funding.

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

Voting

27 net votes
45 up votes
18 down votes
Active

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)

Voting

28 net votes
46 up votes
18 down votes
Active

Goal 3: Advance Translational Research

Harnessing the ongoing ‘natural experiments’ of quality improvement

How do we harness the ongoing “natural experiments” of quality improvement (QI) activities in various healthcare systems to facilitate hypothesis-driven research, improve scientific validity to address questions in clinical trials, and implement and disseminate research results? • Current restrictions in human subjects research regulations • Diversity in approaches and methodology rigor to QI initiatives across different ...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 :

• Publication of QI initiatives in peer-review journals

• Wider dissemination and adoption of best practices

• Establishment of methodologically rigorous QI programs with viable career pathways

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

Voting

-2 net votes
11 up votes
13 down votes
Active

Goal 3: Advance Translational Research

Improving heart, lung, blood, sleep Health Outcomes for Minority and Underserved Men

What are the best strategies to improve implementation of evidence-based practices (EBP) to enhance effective health risk communication strategies among racial and ethnic minority males and underserved men? Examples of several issues that need to be addressed are: • Need for better definition of the role of families/communities in EBP (as co-therapists). • Requires less system fragmentation • Need for improved measurement, ...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 :

Our improved ability to develop, implement and disseminate EBPs tailored specifically for men in health disparity populations may help us move beyond current obstacles in addressing health inequities and improve health outcomes.

Some current challenges:

• High blood pressure affects more than 40 percent of African Americans.

• The odds for stroke, the third leading cause of death in the United States, are especially high for African American men at 70%.

• African Americans are about 50% more likely to experience stroke than Caucasians.

• Sleep apnea is seen more frequent among men than among women, particularly among African-American and Hispanic men.

• Life expectancy for African American men is 4.7 years less than for white men (2010).

• Native American men have an average life expectancy of 71 years old compared to white men who have an average life expectancy of 76.5 year.

Feasibility and challenges of addressing this CQ or CC :

• Shifting demographics of race as well as ageing of the population in this country will have a major impact on the utilization, organization and delivery of health care.

• Country acknowledges significant economic burden of health inequities in the U.S. in the near future.

• Hospitals and health systems are working hard to align quality improvement goals with disparities solutions. Opportunity to leverage these efforts for the development and implementation of targeted health disparities initiatives is timely.

• HL has a number of large population-based studies (such as JHS, Strong Heart, Hispanic Community Health) that could be leveraged to specifically identify EBP for wider implementation and dissemination to underserved areas.

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

Voting

14 net votes
32 up votes
18 down votes
Active

Goal 3: Advance Translational Research

Addressing Unrecognized and Over Diagnosis of COPD

How can we create precision diagnostics for COPD in practice settings that will help inform the transition from screening to better diagnosis and treatment strategies and that will help identify patients or communities at highest risk for unrecognized or over diagnosed COPD.

Submitted by (@jsullivan)

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

Details on the impact of addressing this CQ or CC :

About 12 million individuals are estimated to have undiagnosed COPD and in most cases patients aren’t diagnosed until they have lost over half of their lung function leading to worse outcomes short and long term. Conversely there are challenges with over and mis diagnosed COPD that can result in over treatment and incorrect treatment. Fine tuning screening, diagnostic and management tools can result in earlier and proper identification of disease, earlier initiation of risk mitigation and/or treatment strategies and improved health outcomes as well as improved efficiencies in the healthcare system.

Name of idea submitter and other team members who worked on this idea : COPD Foundation, Nancy Leidy, COPDF MASAC

Voting

11 net votes
12 up votes
1 down votes
Active

Goal 1: Promote Human Health

Qigong and Tai Chi for Chronic Disease Prevention

Non-pharmacological interventions for pain and stress have gained tremendous momentum. Mind-Body Practice -- Qigong and Tai Chi -- are group based and inexpensive to implement. The evidence base suggests that these practices are safe and effective for a multitude of preventable chronic disorders.. THE QUESTION: Given safety and efficacy, should there be vigorous research on implementation of Qigong and Tai Chi and ...more »

Submitted by (@rogerjahnke)

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

Details on the impact of addressing this CQ or CC :

What can we do to assure that safe, effective, inexpensive non-parmacological approaches like Qigong and Tai Chi become widely diffused into communities, agencies, organizations, schools, health systems and businesses.

Feasibility and challenges of addressing this CQ or CC :

We have participated in a number of studies that have contributed to the evidence base for Mind-Body Practice as a safe and effective non-pharmacological programming.

 

The key -- group based. For the financing, group based is inexpensive. For the efficacy group based supports compliance.

Name of idea submitter and other team members who worked on this idea : Dr Roger Jahnke, http://IIQTC.org

Voting

2 net votes
33 up votes
31 down votes
Active

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 »

Submitted by (@murry0)

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

Voting

23 net votes
45 up votes
22 down votes
Active

Goal 3: Advance Translational Research

Best Implementation Strategies

What are the best implementation strategies to improve adherence to clinical practice guidelines, protocols, and other evidence-based practices that actually lead to the elimination of inequities in preventable disability and death from heart, lung, blood, and sleep 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 : NHLBI Staff

Voting

12 net votes
20 up votes
8 down votes
Active

Goal 2: Reduce Human Disease

Bringing Personalized Biochemistry and Biophysics to Bear on Problems of Personalized Heart, Lung and Blood Medicine

Precision medicine will provide unprecedented opportunities to tailor health care based on knowledge of personal patterns of genetic variations. These variations usually impact protein or RNA sequences, resulting in altered properties. These alterations can result in increased susceptibility to a particular disease or intolerance to common therapeutics. To take full advantage of knowing a patient’s set of gene variations, ...more »

Submitted by (@chuck.sanders)

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

Details on the impact of addressing this CQ or CC :

As detailed in the attached review (Kroncke et al. Biochemistry 2015, 54, 2551−2559) the successful practice of personalized medicine will in many cases require a molecular-level understanding of the nature of the defects that are caused by disease-predisposing genetic variations. As widespread personal genome sequencing becomes routine, numerous genetic variations (many millions) of uncertain significance will be discovered. Using both experimental and computational tools associated with the fields of biochemistry, biophysics, and structural biology it is in many cases possible to ascertain whether a newly-discovered gene variation adversely impacts a critical protein or RNA function and, if so, how. Among various clinical applications this information can be used (i) to project whether a patient not currently showing symptoms for a particular disease is likely to present with that disease in the future (sometimes enabling prophylactic therapy), (ii) to help establish the molecular etiology of a disease currently afflicting the patient, and (iii) to guide the therapeutic strategy pursued for that patient.

Feasibility and challenges of addressing this CQ or CC :

My lab is already participating in a project (RO1 HL122010) with two other labs (those of Drs. Jens Meiler--Vanderbilt and Alfred George--Northwestern) to develop personalized biochemical and biophysical approaches for application to genetic variations impacting the KCNQ1 gene, potentially predisposing patients to long QT syndrome, a cardiac arrhythmia. However, our project deals with one gene and one disorder only. There clearly is a need for improved and expanded communication and collaboration between those practicing personalized/precision medicine and those who are well-equipped to provide medically actionable molecular insight using the approaches of personalized biochemistry, biophysics, and structural biology.

Name of idea submitter and other team members who worked on this idea : Charles R. Sanders, Prof. of Biochemistry, Vanderbilt University (With Drs. Alfred George--Northwestern University and Jens Meiler--Vanderbilt University)

Voting

-2 net votes
9 up votes
11 down votes
Active

Goal 2: Reduce Human Disease

DEVELOPMENT OF A PERSONALIZED APPROACH TO SLEEP AND CIRCADIAN DISORDERS

There is developing evidence of major individual differences in pathways to different common sleep disorders such as obstructive sleep apnea. Moreover, there is evidence of different clinical presentations of disease and different outcomes. For example, some subjects with obstructive sleep apnea who get excessive sleepiness while others do not. The latter are still at risk for other consequences of the disorder such ...more »

Submitted by (@jnoel0)

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 strong rationale for application of a personalized approach to sleep disorders. This requires approaching this question using multiple domains as in other areas of medicine—clinical features, physiological factors, application of the –omic approaches, genetics. The impact of this will be several:

 

a. A new way to classify sleep disorders.

b. Identification of subgroups of patients with apparently the same disorder who will have different outcomes of therapy.

c. Identification of subgroups of patients who will have different approaches to diagnosis.

d. Identification of subgroups of patients with apparently the same disorder who will have different therapeutic approaches.

Feasibility and challenges of addressing this CQ or CC :

These sleep and circadian disorders are extremely common. There is a risk infrastructure for this type of research based on the large number of accredited sleep centers in the United States that could be used for subject recruitment and who can adopt similar techniques. There is also a rich set of data obtained from sleep studies that could be used to identify new patterns that reflect different subgroups of subjects. These studies need to be based on clinical populations of patients who present with the different disorders rather than on population-based cohorts.

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

Voting

167 net votes
220 up votes
53 down votes
Active