Showing 11 ideas for tag "biomarkers"

Goal 3: Advance Translational Research

Maximizing Previous Investment in Existing Cohorts

Everyone would like to see integration of genomic, metabolomic, epigenomic, proteomic, transcriptomic, etc. data analyzed in the context of clinical disease, environmental influences, and even end-organ effects (lung versus heart or blood as an example). Rarely can this occur on small cohorts, but rarely are funds available to take maximum use of existing large cohorts and the samples and information collected within... 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

The impact would be huge as it would leverage already extremely expensive cohorts to maximum potential, allowing for exploration into clinical subphenotyping, disease mechanisms, personalized medicine, surrogate endpoints, biomarker exploration, etc. Maximizine output on previous investment is the clearest impact, since even simple analysis in a large number of samples adds up to a very hefty sum. Additionally, data from samples becomes more valuable with longitudinal follow-up of available subjects.

Feasibility and challenges of addressing this CQ or CC

The challenges include the expense of analysis in large cohorts and the ability to attract and fund high level biostatistical faculty at top-notch institutions and get them engaged fully in the problem. Biostatisticians of high caliber will not engage without funding and without an ability to “train” students using the data and explore their own research interests within the context of the overall clinical problem. Funding mechanisms that are large (to allow for deep phenotyping of cohort samples on multiple platforms in multiple sample types) and that seek to generate solid and ongoing collaborations between the data generators and the data analyzers must emerge.

Name of idea submitter and other team members who worked on this idea Wanda K. O’Neal, PhD

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22 net votes
34 up votes
12 down votes
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Goal 3: Advance Translational Research

Identifying Biomarkers of Chronic Lung Diseases

What are the biomarkers that identify expression and progression of specific subtypes of chronic lung disease?

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

Details on the impact of addressing this CQ or CC

Most chronic lung diseases, including COPD, do not have biomarkers that reflect disease pathogenesis accurately. Readily measurable biomarkers, especially in peripheral blood, would be key tools for clinical trials and studies of disease heterogeneity.

Feasibility and challenges of addressing this CQ or CC

The most useful chronic lung disease biomarkers would be proteins, metabolites, or gene expression measurements in peripheral blood. Defining useful peripheral blood biomarkers that reflect lung disease pathogenesis will require validation that the lung disease process can be captured in peripheral blood measurements.

Name of idea submitter and other team members who worked on this idea Ed Silverman, James Crapo and COPDGene Executive Committee

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42 net votes
62 up votes
20 down votes
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Goal 3: Advance Translational Research

Maximizing anti-tumor immunity following allogeneic HCT with biomarkers

Allogeneic hematopoietic cell transplantation (allo-HCT) is one of the most effective forms of tumor immunotherapy available to date. Allo-HCT can be life-saving for patients with aggressive malignancies that cannot be cured through other strategies. The immunotherapeutic efficacy of allo-HCT depends on donor T cell recognition of alloantigens on leukemic cells, which is known as the graft-versus-tumor effect (GVT). No... 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

Allo-HCT represents the only curative therapy for a number of malignant disorders but often results in serious complications, including GVHD. Because GVHD is such a potentially devastating post-transplant complication and because we want to be able to separate GVHD from the GVT effect, it is crucial to try to determine a specific biological pattern link to the favorable GVT effect. The focus of this critical challenge will be to develop a novel, non-invasive GVT signature in patients undergoing HCT. If successful, this will have a major impact, because a GVT-specific proteomic signature may facilitate the clinical therapeutic decision of rapid taper of immunosuppression or increased immunotherapies. The ability to identify patients who will not develop GVT early post-transplant has important therapeutic consequences, including preventative care with donor-lymphocyte infusion (DLI) or tumor-specific vaccines or T cells expressing chimeric antigen receptors (CARs). Equally important is the identification of patients who will develop GVT without GVHD, potentially enabling more rapid tapering of immunosuppressive regimens and thereby promoting even more the GVT reaction as well as reducing long-term toxicity in these patients. With this diagnostic tool, the HCT community may plan to develop preemptive therapeutic trials. In addition, the biomarkers may represent potential GVT-specific therapeutic targets to maximize GVT and/or immunotherapies.

Feasibility and challenges of addressing this CQ or CC

Using proteomics, several GVHD biomarkers were recently identified and validated. For example, high suppression of tumorigenicity 2 (ST2) plasma concentrations were significantly associated with the incidence of GVHD and transplant-related mortality in recipients of unmanipulated graft and cord blood transplants. Consequently, the Blood and Marrow Transplant Clinical Trial network is currently pursuing therapeutic interventions for newly diagnosed GVHD patients based on GVHD biomarkers risk-stratification. Thus, discovering and validating biomarkers post-HCT is feasible. However, the challenges with GVT-specific biomarkers are three-fold: 1) the absence of phenotype, as the only way to define clinical GVT without GVHD, is the absence of relapse and no GVHD post-HCT; 2) the paucity of samples to study GVT, ideally samples following DLI or nonmyeloablative conditioning preparative regimens that permit stable engraftment of donor hematopoietic cells but have little or no direct tumoricidal activity should be available; and 3) the relative lack of knowledge of the biology of GVT. These represent important challenges to solve. In sum, the recent successes of cancer immunotherapies, particularly for the treatment of hematological malignancies, have stimulated interest in the potential widespread application of these approaches, and biomarkers to predict and monitor the responses are required.

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

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32 net votes
52 up votes
20 down votes
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Goal 3: Advance Translational Research

Tools to facilitate availability and safe use of innovative blood products and their analogs

Novel blood products are being developed based on innovative science (e.g., ex vivo manufactured RBC and platelets, and platelet and plasma derived hemostatic products). However, there is a significant lag in the development of appropriate tools and model systems, which poses a challenge when evaluating such products for regulatory approval.

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

Details on the impact of addressing this CQ or CC

The rapid advancement in science and technology has identified pathways for ex vivo manufacturing of RBC and platelets; platelet and plasma derived hemostatic products and recombinant coagulation factors, etc. However, these novel products have to be evaluated for their safety, efficacy, purity and potency as part of regulatory approval process. Because the new products are manufactured using innovative technologies some of the existing tools for their evaluation are inadequate. Therefore, future investments in the development of necessary predictive tools (I.e. regulatory science tools) in areas such as the following will positively impact the availability and safe use of innovative blood products and their analogs: 1) the development of analytical and biochemical assays, 2) animal models for product safety and efficacy, 3) product quality-associated biomarkers to characterize storage lesions of RBC and platelets and 4) functional assays and molecular and bioinformatics models that can predict the success of novel blood products both during manufacturing and with respect to clinical patient outcomes.

Feasibility and challenges of addressing this CQ or CC

This initiative is feasible as investigators in blood organizations, academia and government are already working independently towards this goal in their defined areas of study. However, a coordinated effort among these independent entities could help in the faster development of necessary regulatory science tools to optimize care of individual patients and patient groups.

Name of idea submitter and other team members who worked on this idea Office of Blood Research and Review, CBER, FDA

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12 net votes
17 up votes
5 down votes
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Goal 3: Advance Translational Research

Establish COPD Biomarkers

Specific biomarkers to monitor COPD disease activity are needed.

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

Details on the impact of addressing this CQ or CC

Much is understood about the pathogenesis of COPD at the cellular and biochemical level. There is no established way these insights can be used to test or implement new medicines. An explicit and economical set of procedures need to be established that will facilitate the development of new medicines and guide their clinical use.

Feasibility and challenges of addressing this CQ or CC

Many very small studies have identified biomarkers that relate to COPD activity in large groups of patients. There is no clear regulatory path for these insights to lead to tests that can be used with confidence in the development and implementation of novel treatments. Realistic regulatory pathways and criteria should be adopted to facilitate the development biomarkers of disease activity in COPD.

Name of idea submitter and other team members who worked on this idea COPD Foundation, COPD Biomarkers Qualification Consortium

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15 net votes
17 up votes
2 down votes
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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 »

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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Goal 3: Advance Translational Research

Molecular determinants of vascular wall development and aneurysm formation that can be used as markers for early diagnosis

To increase the potential of translating basic research discoveries into the clinic, there is a need to discover molecular biomarkers that confer risk for aneurysms and vascular dissections. The creation of a nation-wide biorepository of well-defined tissue and plasma samples along with research utilizing these tissue samples employing state-of-the art proteomics, genomics and development of appropriate mouse models will... 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

The challenge is the coordination of all components of the Project (i.e. development of a national biorepository along with coordination of proteomics and genomics analysis as well as proof of concept in animal models).

Feasibility and challenges of addressing this CQ or CC

This process is not feasible via the R01 funding mechanisms. The feasibility of addressing this critical challenge is excellent provided adequate resources are provided.

Name of idea submitter and other team members who worked on this idea Dudley Strickland and Selen Catania Muratoglu

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5 net votes
7 up votes
2 down votes
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Goal 3: Advance Translational Research

Biomarkers of asthma

Need to develop and integrate biomarkers of asthma into phenotype/endotype-driven asthma management algorithms

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 Asthma and Allergy Foundation of America (AAFA)

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1 net vote
1 up votes
0 down votes
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Goal 3: Advance Translational Research

Drug Hypersensitivity Databases

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:

Drug Hypersensitivity is a growing concern for patients who are unprotected against potentially severe and lethal reactions. It would be important to generate databases to characterized the different drug reactions, their... more »

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

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-7 net votes
11 up votes
18 down votes
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Goal 3: Advance Translational Research

Detection of inflammatory monocytes as a biomarker of CVD

Coronary artery disease (CAD), of which atherosclerosis is a major contributor, costs the United States $108.9 billion each year. While a number of conventional risk factors such as smoking, diabetes and hypertension have been associated with CAD, their predictive performance is poor in the prevention of acute coronary syndrome (ACS). Despite the prevalence of ACS in our society, there are currently no molecular biomarkers... 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

Need more opportunities to put forth innovative diagnostic and therapeutic solutions than currently vetted through the CTSC process.
We have developed the Artery-on-a-chip (A-chip), currently in a research tool format, which accurately measures the extent of inflammatory monocyte activation in a whole blood sample by shearing it along a molecular sensor and enumerating monocyte capture.

Name of idea submitter and other team members who worked on this idea Scott I Simon, Greg Foster, Ehrin Armstrong

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-6 net votes
8 up votes
14 down votes
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