Mount Sinai team to study sickle cell triggers in everyday life
$4.1M grant aimed at advancing understanding of environment
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A research team at the Icahn School of Medicine at Mount Sinai has received a $4.1 million grant to investigate how everyday environmental exposures — from air pollution and temperature to food, housing, and stress — may affect the health of people with sickle cell disease (SCD).
The five-year study aims to shed light on why the impact of SCD can vary widely from person to person, and to identify environmental factors that may worsen symptoms and contribute to disease complications.
The grant, from the National Institutes of Health’s National Heart, Lung, and Blood Institute, will support research led by Mount Sinai’s Department of Emergency Medicine.
“We have heard time and time again from our patients: their lives impact their disease, and vice versa,” Sarah McCuskee, assistant professor at Mount Sinai and the study’s principal investigator, said in a university news story. “But until now, how daily life impacts sickle cell disease hasn’t been studied very much.”
Pollution linked to inflammation
SCD is caused by genetic mutations that cause the body to produce abnormal forms of hemoglobin, the protein that carries oxygen in red blood cells. As a result, red blood cells become rigid and take on a sickle shape, making them more likely to die prematurely (hemolysis) or become trapped in blood vessels. This can block blood flow and reduce oxygen delivery to tissues.
People with SCD commonly develop anemia (low levels of healthy red blood cells and hemoglobin), which can cause fatigue, pallor, and dizziness. Blocked blood flow can trigger vaso-occlusive crises, episodes of severe pain and inflammation that occur when tissues stop receiving oxygen.
The manifestations of SCD vary considerably among patients. Research from McCuskee’s team has suggested that the characteristics of a person’s social and physical environment may be linked to differences in inflammation and disease manifestations, and that air pollution may lead to inflammatory changes in adults with SCD.
Other research has shown that exposure to air pollutants is associated with a higher risk of hospitalization among children with SCD.
The new project, titled “MAP SCD: Mechanisms for Actionable Place-Based Drivers of Health in Sickle Cell Disease,” will focus on environmental and social conditions that could influence health. These include neighborhood factors such as crime, along with access to healthy food, temperature, airborne pollution, and housing conditions.
Researchers will combine biological information from blood samples previously provided by people with SCD and stored in the Sinai Sickle Cell Collaborative biorepository with data describing participants’ environmental exposures. Satellite-based models will be used to estimate factors such as air pollution, temperature, food, and neighborhood-level stressors.
The study will also capture real-time exposures in participants’ daily lives. Portable sensors will record the fine particles people breathe, and researchers will collect information about diet and stress. These data will be compared with biological measures of hemolysis, inflammation, and organ damage to the kidneys, heart, and lungs.
The goal is to identify exposures that are both biologically relevant and potentially modifiable, which could eventually help clinicians provide more personalized advice to people with SCD.
“We are measuring everyday exposures to understand their impact on health in people with sickle cell disease and this is among the first prospective studies of exposures in sickle cell disease to ever be done,” McCuskee said. “We plan to develop tools based on our results to help clinicians counsel patients.”
The researchers also intend to make the study’s findings accessible to the public. Among the planned outputs are maps illustrating environmental exposures across neighborhoods, which will be created in partnership with members of New York’s sickle cell community.
“We hope that the methods we develop could form a model for investigating and understanding other chronic and genetic illnesses,” McCuskee said.
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