Addressing Chronic Wound Trajectories Through Social Genomics Research (R01-Clinical Trial Optional)

Funder: Department of Health and Human Services

PA-17-492

Posted Date: September 27, 2017

Chronic wounds affect over five million Americans each year, resulting in over $20 billion in health care costs. Individuals with disabilities and diabetes, as well as the elderly, have the highest risk of developing chronic wounds. Chronic wounds are complex and multidimensional and, as such, an effective wound care strategy would be strengthened by expanding beyond a focus on healing the wound (i.e., repairing the skin and underlying tissue) to embracing an approach that focuses on healing the person with the wound (i.e., addressing the patient as a whole). The potential benefit of this holistic approach is supported by studies that have identified chronic wound-related stressors such as social isolation, reduced independence/inability to perform activities of daily living (ADLs), poor body image, and low self-esteem as factors that negatively impact chronic wound healing. Positive experiences, such as improved self-efficacy or social support from family, community, or other forms of peer interaction, have been reported to not only improve well-being but also to contribute to enhanced wound healing and reduced wound recurrence. The immune system and associated inflammatory processes are hypothesized to underlie this connection between the social environment and outcomes in chronic wound patients, however, the mechanisms that occur at the molecular level remain understudied.

The field of social genomics focuses on how the social environment – including a person’s subjective perception of the social environment – influences gene expression, and how this gene expression in turn may impact health outcomes. For example, studies of adverse social conditions, including social isolation (a well-studied risk factor for chronic illness and mortality), low socioeconomic status (SES), and chronic stress have revealed a common pattern of leukocyte differential expression of hundreds of gene transcripts, characterized by increased expression of pro-inflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Conversely, studies of persons experiencing positive well-being exhibited a reverse gene expression pattern, further reinforcing the reciprocal link between the social and biological determinants of health outcomes.

A better understanding of how the social environment and underlying molecular mechanisms intersect to influence health outcomes in individuals with or at risk for developing chronic wounds is needed.  Gene expression in this context remains understudied. Additionally, epigenetic modifications (such as DNA methylation), which are known to be triggered by environmental influences, have not been sufficiently addressed, nor is there information on the microbiome, which is known to play a role in the immune system and inflammation. Filling this gap is critical in order to provide the evidence base for development of targeted, individualized interventions aimed at modifying the social environment and taking into account a person’s biology and social experiences, perspectives, and preferences.

Research objectives include, but are not limited to, those that address:

  • Social environmental factors and experiences associated with chronic wound trajectories; corresponding influence of these factors and experiences on molecular mechanisms (e.g., gene expression, epigenetic modifications, microbiome alterations, etc.).
  • Potential biomarkers that reflect molecular mechanisms in response to the social environment and can be used as prognostic indicators of poor wound outcomes
  • Downstream products (e.g., protein and metabolic products) of genomic processes that occur in response to an adverse social environment in persons with chronic wounds
  • Biobehavioral interventions that target social environmental influences thus reducing chronic wound risk or improving healing outcomes; use of gene expression or other omic approaches to monitor intervention response

When designing studies, applicants should additionally consider variables such as age (and associated changes in the immune system that occur as individuals age), comorbidities, nutritional status, and other variables that may independently play a role in wound healing. Cultural practices and preferences should also be considered.

This FOA is intended to encourage clinical studies only; it is not intended for studies in animal models.  Studies using drugs or biologics, dietary supplements, herbal medicines, or other complementary and alternative interventions are also not appropriate. Potential applicants are encouraged to contact the NINR Scientific/Research Contact to discuss proposed research ideas prior to submission of the application.

Interdisciplinary collaborations that include nurse scientists in the project team are strongly encouraged.

See Section VIII. Other Information for award authorities and regulations.

https://grants.nih.gov/grants/guide/pa-files/PA-17-492.html#_Section_III._Eligibility

 

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