Project Details
Description
PROJECT SUMMARY
The objective of this proposal is to understand how immune responses in children with sickle
cell disease (cwSCD) are shaped by exposures in their local environment and lead to disparate
health outcomes. The rationale underlying this proposal is that our prior work demonstrates that
cwSCD have unique alterations in their blood inflammatory transcriptional profiles and upper
airway microbiomes at baseline with further perturbations during acute complications. We have
also shown that the public health exposome (PHE), which includes stressors from the natural,
built, social, and policy environments, influences inflammation in chronic diseases. The
proposed research is significant because SCD disproportionally impacts underrepresented
minority populations with many children frequently exposed to and challenged by multiple
negative social determinates of health. The central hypothesis is that the PHE is associated
with altered inflammatory signaling in cwSCD leading to increased frequency of acute
complications. The central hypothesis will be tested by pursuing two specific aims: 1)
Characterize SCD baseline immune signatures and 2) Link environmental and socio-
demographic factors from the PHE 4.0 database to SCD outcomes at the individual, community,
and population-levels. We will pursue these aims using sophisticated transcriptional and
proteomic profiling of immune signatures combined with a novel database of real-time PHE data
and well-characterized clinical data. Our interdisciplinary team of experts in immunology,
microbiology, and public health along with hematology, pulmonology, and ID specialists
combines complementary clinical and research expertise to take a new approach to study
outcomes in cwSCD. The expected outcome of this work will establish a unique profile of
immune signatures integrated with the PHE to generate an unparalleled dataset of biologic
data with societal and environmental factors that influence health in cwSCD. The long-term
goal is to integrate findings with a comprehensive assessment of the airway and gut
microbiomes and hormonal stress responses from this cohort and longitudinally evaluate how
immune-environmental factors predict acute complications. Ultimately, we will create
comprehensive phenotypic profiles of cwSCD to help improve prediction, prevention, and
treatment of acute complications in cwSCD that move beyond the current paradigm of
supportive and/or reactive care.
Status | Active |
---|---|
Effective start/end date | 02/1/23 → 01/31/25 |
Funding
- National Institute of Allergy and Infectious Diseases: $222,445.00
- National Institute of Allergy and Infectious Diseases: $212,970.00
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