The Role of Dysbiosis in Cardiovascular, Pulmonary and Hematological Complications During HIV Infection
Dysbiosis is defined as the deviation from the normal resident microbial community composition found in a healthy population of individuals. During early stages of HIV infection, the intestinal epithelial barrier suffers extensive damage, repair of epithelial cells is impaired by altered expression of genes involved in the machinery of regeneration, and many genes involved in inflammation are upregulated. These alterations lead to a general state of dysbiosis, including translocation of microbes and microbial constituents that are normally contained within the gut into the systemic circulation where they can induce inflammation and pathobiology of distal organs. Dysbiosis likely contributes to the cardiovascular, pulmonary, and hematological complications seen in HIV infection and may be an important cause of poor health outcomes. Although dysbiosis is generally associated with gut microbial alterations, microbial imbalance is not unique to the gut. In advanced states of HIV infection, individuals with lower CD4 cell counts have an altered alveolar microbiome characterized by a loss of species richness and diversity, and have increased amounts of signature bacteria associated with chronic lung inflammation after years of antiretroviral therapy (ART). Furthermore, specific metabolic profiles in the lung appear to correlate with bacterial organisms that are known to play a role in the pathogenesis of pneumonia in HIV-infected individuals, suggesting that dysbiosis may have a functional metabolic impact on the lung.
Clinical Centers for the NHLBI's Precision Interventions for Severe and/or Exacerbation Prone Asthma (PrecISE) Networ
The purpose of this funding opportunity is to invite applications to participate in the NHLBI Precision Interventions for Severe and Exacerbation Prone Asthma (PrecISE) Network. This clinical trial network will conduct sequential, adaptive, phase II/proof of concept clinical trials with precision interventions in stratified patient populations. The Network will utilize patient phenotypes and/or endotypes, predictive, and monitoring biomarkers/profiles in sequential adaptive trials to evaluate the most effective precision intervention strategies for this hard to treat patient population. PrecISE will include multiple clinical centers and a single Data, Modeling, and Coordination Center (DMCC). This FOA invites applications for the Clinical Centers (CC) and runs in parallel with a companion FOA (RFA-HL-17-010) that invites applications for the DMCC.
NHLBI Clinical Trial Pilot Studies (R34)
The NHLBI is committed to identifying effective treatments and prevention strategies for heart, lung, blood and sleep disorders by supporting well-executed clinical trials. Although the scientific literature or preliminary data may provide the rationale for conducting a clinical trial, investigators often lack critical information about the intervention, the outcome, or recruitment necessary to design the trial completely. These information gaps can result in trial delays and multiple protocol changes as the trial is implemented, leading to cost overruns or trial termination for lack of feasibility. Further, the suitability and feasibility of new trial designs, which minimize infrastructure and reduce costs may need to be tested in the context of a particular intervention, disease, or venue. Preparatory pilot studies can fill information gaps and address unknowns, thereby improving trial design and knowledge of trial feasibility.
The purpose of this FOA is to support pilot studies for the acquisition of data critical to complete the design of a full-scale trial. The goal is that the proposed R34 pilot studies will yield information that is both necessary and sufficient to permit the design of the clinical trial. Examples of research topics include but are not limited to the following:
- Perform studies to determine the appropriate study population, intervention, or outcome.
- Collect information necessary to estimate available populations, attrition rate, or response rate.
- Refine the intervention.
- Test the feasibility of an outcome or intervention in the field.
- Determine whether adequate adherence to a treatment is achievable.
- Standardize and validate survey instruments.
- Standardize and test effectiveness of training tools.
- Adapt and test a survey instrument or protocol for a population that differs culturally from the population for which the instrument was originally designed.
It is anticipated that, if indicated, applicants will have appropriate U.S. Food and Drug Administration approval and any necessary agreements. This FOA is intended to support applications that address research questions that are within the mission of the NHLBI; research questions addressing prevention or treatment of malignancies are not within NHLBI’s mission. This FOA is not intended to support first-in-human studies. Applications that are first-in-human studies, propose solely to write a protocol or manual, develop infrastructure, are mechanistic, or are animal studies are not appropriate for this FOA.
Dissemination and Implementation Research in Health (R01)
The purpose of this Funding Opportunity Announcement (FOA) is to support innovative approaches to identifying, understanding, and developing strategies for overcoming barriers to the adoption, adaptation, integration, scale-up and sustainability of evidence-based interventions, tools, policies, and guidelines. Conversely, there is a benefit in understanding circumstances that create a need to “de-implement” or reduce the use of strategies and interventions that are not evidence-based, have been prematurely widely adopted, yield sub-optimal benefits for patients, or are harmful or wasteful.
NHLBI TOPMed: Omics Phenotypes of Heart, Lung, and Blood Disorders (X01)
NHLBI’s mission covers many major common diseases, such as heart disease and chronic lower respiratory diseases, which are the first and third leading cause of death in the United States, respectively. NHLBI also supports research on asthma, the most common chronic disease of children in the US, and on many rare but complex anemias including sickle cell disease. While there are established ways to treat these diseases, treatments are often targeting just symptoms or are effective for only a fraction of patients. Better understanding of the underlying pathobiological causes of diseases could lead to more effective ways to prevent or treat many common, complex diseases. Advances in high throughput technologies in the areas of genomics, epigenomics, metabolomics, and proteomics provide an opportunity to accelerate the discovery of the molecular causes of complex diseases. NHLBI’s TransOmics for Precision Medicine (TOPMed) program seeks to apply these omics technologies to heart, lung, and blood (HLB) disorders — generating large volumes of omics data and making those datasets accessible to the broad research community to stimulate discovery research. This FOA is intended to support the production of substantial quantities of omics data using standardized protocols and, following the NIH Genomic Data Sharing Policy, to release the resulting datasets for public access in a uniform data format.
Postdoc-to-Faculty Transition Awards
Awards will provide individuals up to five years of combined support for their research training (maximum of three years) and the initiation of their independent research career (two years). Candidates for this award can be identified any time during the first four years of their postdoctoral fellowship.
This award is intended to provide an opportunity for promising postdoctoral fellows to hone research skills, develop into independent investigators and initiate an independent CF research program. Projects supported by this award may include research at the sub-cellular, cellular, animal or patient levels.
Stipends for this award are based on years of postdoctoral experience. Research support of $10,000 per year is available during the postdoctoral training phase of the award. The faculty phase of the award includes $80,000 for salary support and $30,000 for research support. Indirect costs are not allowed.
U.S. citizenship or permanent resident status is required.