NIMHD Adjunct Investigator Program

National Institute On Minority Health And Health Disparities

Investigators

Linked publications & trials

Abstract

In FY25, we continued to fund 6 adjunct Investigators to conduct health disparities research in their labs. This strategy of funding seasoned health disparities investigators and early career investigators has been exceptionally helpful in creating opportunities and supportive environments for trainees. Stefan Ambs, NCI Dr. Ambs’ group pursued molecular epidemiology and laboratory-based research of prostate and breast cancer with a focus on cancer health disparities and risk factors that alter tumor biology. Currently, genomic risk, including genetic ancestry–inferred risk, is considered a nonmodifiable risk factor for chronic diseases like cancer. As an example, West African genetic ancestry has been linked to an excessive prostate cancer risk among Black men. However, it is unclear whether additional factors play a role in determining this genetic ancestry-related risk. Dr. Ambs’s team hypothesized that examining the interaction of genetic ancestry–inferred risk and stress-related exposures (e.g., neighborhood environment) may allow for multifactorial tailored interventions that account for both genetic and environmental factors. Thus, they investigated whether neighborhood deprivation may modify the association of West African genetic ancestry with prostate cancer risk and mortality. They found that neighborhood environments may modify how West African genetic ancestry is associated with prostate cancer risk (PMID: 39283637)1. Our data indicate that West African genetic ancestry was a greater risk factor for men residing in neighborhoods with high levels of deprivation than for men living in more affluent neighborhoods. The findings suggest that genetically inferred risk is a modifiable risk factor, not determination. Thus, improving the neighborhood environment may alleviate both the prostate cancer burden directly and the risk associated with West African genetic ancestry among men residing in areas with high deprivation. The mechanisms through which chronic stressors may be associated with tumor biologic characteristics, immune response, and health disparities remain insufficiently understood. Hence, the team investigated the proteomic, transcriptomic, and genomic effects associated with multilevel chronic stressors among women with breast cancer. The team found that stress, inadequate social support, perceived racial and ethnic discrimination, and neighborhood deprivation were associated with deleterious biologic and immunologic changes at the genomic, transcriptomic, and proteomic levels both systemically and within the tumor microenvironment in patients with breast cancer (PMID: 39951265). Specifically, they were associated with suppression of the antitumor immune response, systemic inflammation, and deleterious tumor biologic characteristics. These outcomes were particularly pronounced in African American women. These findings suggest that chronic stressor-induced inflammation and immune dysfunction may be associated with increased breast cancer aggressiveness and cancer disparities in health disparities populations. The team concludes that understanding biology as a possible mediator of cancer health disparities can inform prevention and public health interventions. Michele Evans, NIA During FY25, Dr. Jason Ashe was supported by NIMHD funding. Jason Ashe was an outstanding and productive NIMHD-supported postdoctoral fellow. Jason was awarded a Coleman award for a project that will allow him to investigate the role of inflammatory proteins in the connection between spirituality and cardiovascular disease risk. In addition, in July of 2025 he was awarded a Nathan Shock Travel Award for his poster at the NIA Intramural Scientific Retreat entitled Spirituality and Cardiovascular Health among African American and White adults. His publications in this fiscal year focused on the vital relationships between religious coping, a specific psychosocial stressor, race and cardiovascular disease risk. Dr. Ashe also participated in research projects examining loneliness, the current epidemic in the US population. Further research examined medical mistrust and self-rated health in the context of poverty, race, health literacy and a psychosocial stressor. Jason completed his postdoctoral training this summer and transitioned to a tenure-track assistant professor in theology at Emory University. Chandra Jackson, NIEHS Dr. Chandra Jackson’s research continues to focus on environmental and social epidemiology related to sleep and cardiometabolic health. Her team published two book chapters – one that summarizes the environmental determinants of sleep health and one that discusses sleep as a modifiable, essential pillar of health that can be promoted to advance health equity. Moreover, aligned with the NIEHS critical research area of emphasis related to environmental health disparities, the group published a commentary to help guide environmental health disparities scientific inquiry. Dr. Jackson’s team has explored how environmental exposures influence sleep health. Allergens are expected to increase due to climate-related factors like air quality and are likely related to sleep. We investigated the relationship between indoor bedroom allergen exposure and sleep outcomes using National Health and Nutrition Examination Survey data. Elevated pet allergens were associated with trouble sleeping among Hispanic/Latino individuals, and fungal allergens were linked to sleep disorders and increased sleep medication use, especially among female and individuals with moderate socioeconomic status. Another environmental feature that plays a role in changing weather patterns is greenspace. Using data from the NIEHS Sister Study, they found that lower proximity to greenspace was generally associated with poorer sleep health. However, for women living in socioeconomically deprived neighborhoods, this association was reversed, possibly reflecting unintended negative consequences of greenspace development among groups with higher susceptibility. Dr. Jackson also examined racial and ethnic differences in perceptions of neighborhood walkability and their impact on sleep using National Health Interview Survey data. Positive walkability features were more frequently reported by Asian adults, while negative features such as crime were more often reported by Latine and Black adults. Moreover, neighborhood walkability was associated with sleep health. Dr. Jackson’s research group also published work demonstrating associations between physical environmental exposures and respiratory and cardiometabolic health. Specifically, our literature review on artificial light at night (ALAN) exposure synthesized findings from 2000 to 2024, identifying associations with Type 2 diabetes mellitus (T2DM) and the role of sleep, physical activity, and dietary behaviors as mediators. They emphasized the need for future research to consider light characteristics like timing, wavelength, and individual sensitivity. Additionally, Dr. Chandra Jackson contributed to an American Thoracic Society workshop and resulting report that highlighted the negative impact of environmental hazards on respiratory and sleep health, recommending multi-level intervention strategies. The group investigated social factors in relation to sleep health outcomes. First, in a study using data from the Study of Environment, Lifestyle and Fibroids (SELF), we investigated how a range of social stressors cumulatively affected sleep health among Black female individuals, revealing the potential impact of multiple stressors on sleep health among this previously understudied population. In a study also using SELF data, darker-skinned Black female adults were more likely to experience sleep disturbances compared to lighter-skinned peers. Extending their prior work about the neighborhood environment and differences by race along with ethnicity, they published work that demonstrated that individuals living in highly racially and ethnically segregated neighborhoods experienced more favorable sleep health. These unexpected results are likely related to perceived neighborhood social cohesion in more homogenous neighborhoods, which aligns with our separate study showing that higher perceived neighborhood cohesion was associated with better sleep. Another health-promoting social factor, social support mitigated sleep-related challenges among a Bhutanese population in the U.S. in our study of a community-cohort in Ohio. They also investigated occupational factors that differ by race and ethnicity in relation to cardiovascular outcomes. Dr. Jackson’s group also published two clinical research studies. They identified that healthcare access modified the relationship between COVID-19 infection and sleep health. She also contributed to a consensus statement with a multidisciplinary panel where we highlighted the heterogeneity of obstructive sleep apnea (OSA) and treatment responses. In one methodological study using Sister Study data, she evaluated the reliability of self-reported versus objectively measured BMI across educational and racial along with ethnic groups. Despite some variation in measurement error that was higher among Black and Latina women with higher educational attainment compared to White female and female with lower educational attainment, we found strong agreement in BMI classification, supporting the validity of self-reported data in this cohort. Tiffany Powell Wiley, NHLBI The Powell-Wiley laboratory continues to make progress on the group’s three main research goals in targeting cardiovascular health disparities in high-risk, resource-limited communities. Their first goal is to delineate mechanisms by which chronic stressors influence the development of cardiovascular disease. For instance, prior studies suggest a plausible connection between amygdala activity as a marker of chronic stress-related neural activity, hematopoietic tissue activity, and cardiovascular events; however, the underlying biological mechanisms linking these relationships are incompletely understood. Chronic stress is also thought to modulate epigenomic modifications. Therefore, they studied the associations between amygdala activity (left (L), right (R), maximum (M), and average (Av) AmygA), and splenic (SpleenA), and bone marrow activity (BMA) as determined by 18Fluorodeoxyglucose (FDG) on Positron Emission Tomography/Computed Tomography (PET/CT) scans. Subsequently, we assessed how these markers of chronic stress and hematopoietic activity relate to the DNA methylation of stress-associated genes in a community-based cohort of African American individuals from Washington D.C. at risk for CVD. Among 60 participants (93.3% female, mean age 60.8), M-AmygA positively associated with SpleenA, but not BMA. M-AmygA and SpleenA were associated with both IL-1β and TNFα. Decreased M-AmygA, SpleenA, IL-1β, and TNFα were associated with methylation of NFκB1 at cg07955720 and STAT3 at cg19438966. Our findings suggest a potential association between AmygA, SpleenA, and pro-inflammatory cytokines in the setting of chronic stress, suggesting an adverse hematopoietic effect. Furthermore, findings reveal associations with epigenetic markers of NFκB and JAK/STAT pathways linked to chronic stress. These results were published in Brain Behavior and Immunity Health. The second goal is to identify methods for incorporating digital health technology into interventions addressing behaviors associated with cardiovascular health in resource-limited neighborhood environments. The team worked in an iterative process to implement Step It Up, a digital health intervention targeting African-American women living in resource-limited Washington, DC communities. This intervention was developed based on the socioecological framework for physical activity. They are now implementing the 6-month physical activity intervention where we use a Sequential Multi-Assignment, Randomized Trial (SMART) approach to compare the effects on physical activity of place-tailored remote messaging to standard remote messaging in a digital health intervention. This study uses novel statistical approaches to account for the adaptive strategy. Effects of physical activity changes on CVD risk biomarkers, including immune cells important in atherogenesis and affected by chronic stress, are being characterized. This protocol was developed in partnership with a Washington, DC-area community advisory board to ensure intervention feasibility and acceptability to community members; the advisory board provides ongoing feedback on the study implementation. For the last group of participants enrolled into this protocol, they are doing cardiac MRI and body composition MRI at baseline and 6-month follow-up to determine the effects of the intervention on cardiac function and adiposity. We have currently enrolled 257 of the 325 target participants for the study (the enrollment target was increased to allow for enrollment of a target of 35-40 participants who undergo the imaging measures). Third goal is to identify and characterize physiologic pathways influenced by the chronic stress that comes from living in adverse neighborhood conditions, ultimately elucidating potentially novel pathways linked to cardiovascular risk phenotypes and most responsive to targeted health behavior interventions. For this aim, we are objectively measuring physical activity, sedentary behavior, and neighborhood stress using accelerometers, GPS, and real-time perceived ecological momentary assessment via smartphone apps and linking these to biological measures in a sample of White and African American female individuals in Washington, DC, neighborhoods. The primary aim of this protocol is to test the hypothesis that living in adverse neighborhood social conditions is associated with higher stress-related neural activity among healthy African American and White female adults living in high or low socioeconomic status neighborhoods in Washington, DC. A secondary objective is to test the hypothesis that residing in adverse neighborhood social environment conditions is related to differences in vascular function. The final aim of this protocol is to test the hypothesis that adverse neighborhood social environment conditions are related to differences in immune system activation. For each of the study aims, we will examine whether objectively measured physical activity modifies any of the relationships. Since 2022, 65 of the 90 target participants have provided complete data for this protocol. While the research team has conducted data collection for this protocol, we have also examined potential markers of innate immune system activation in the setting of adverse social environments using translational studies. They have investigated common signaling pathways involved in natural killer (NK) cell dysfunction related to obesity and hyperlipidemia in African American women from under resourced neighborhoods. We determined in freshly isolated NK cells that obesity and measures of adverse social determinants were associated with a shift in NK cell subsets away from CD56dim/CD16+ cytotoxic NK cells. Using ex vivo data, they identified LDL as a marker related to NK cell function in an African American population from under resourced neighborhoods. Additionally, NK cells from African American women with obesity and LDL-treated NK cells displayed a loss in NK cell function. Comparative unbiased RNA-sequencing analysis revealed DUSP1 as a common factor. Subsequently, chemical inhibition of Dusp1 and Dusp1 overexpression in NK cells highlighted its significance in NK cell function and lysosome biogenesis in a mTOR/TFEB-related fashion. The data demonstrates a pathway by which obesity and hyperlipidemia in the setting of adverse social determinants may relate to NK cell dysfunction, making DUSP1 an important target for further investigation of health disparities. Anne E. Sumner, MD, NIDDK In the last year has contributed significantly to population health in 2 key areas: a) Improved screening for diabetes, and b) Public health-understanding the role of body size in identifying best treatments and prevention of diabetes. Improved Screening for diabetes: First, for improving screening for diabetes, she has proven that G6PD deficiency leads to a lowering of A1C levels independent of degree of glycemia. This work was done in collaboration with NHGRI. The manuscript, HbA1c underperforms in identifying abnormal glucose tolerance in the presence of G6PD deficiency: insight from the Africans in America study, is under re-review by PLOS One. Second, she demonstrated that the criteria the International Diabetes Federation (IDF) is advocating for that the 1-h OGTT replaces the 2-h OGTT. The IDF has proposed that using the single determination of 1- postload glucose of ≥209 mg/dL will identify diabetes or ≥155 md/dL for prediabetes (also known as intermediate hyperglycemia), leaves a significant proportion of Africans undiagnosed and therefore untreated. She has, together with her research team, submitted to the journal, Diabetes Research and Clinical Practice, which is the official journal of the IDF, a Commentary entitled: Call for Modification of the Intermediate Hyperglycemic classification of the 1hour-Oral Glucose Tolerance Test which proposes the simple addition of fasting glucose≥ 100 mg/dL to the criteria, dramatically improves detection. This Commentary is under review. This commentary was a lead research project of the 9th NIMHD-NIDDK-Rwandan Health Program fellow, Dr. Simon Pierre Bigirimana. Third, due to the research conducted in the Section of Diabetes, Nutrition, and Health, she has been asked to serve on a key task force, specifically: The Lancet Diabetes & Endocrinology Commission - Global Consensus for Defining and Diagnosing Prediabetes. Public health understanding of the role of body size in identifying the best treatments for diabetes. She and her team have shown that in populations with a high rate of diabetes in the nonobese, beta-cell insufficiency rather than insulin resistance is the major cause. This is important because Africans (and Asian Indians) are examples of such populations and they need to be screened for diabetes even in the absence of obesity. Therefore, screening guidelines need to be adjusted to reflect the need to screen populations for diabetes even in the absence of obesity. Further, in the presence of beta-cell insufficiency, even small amounts of weight gain which remain below the threshold for obesity, can significantly increase the severity of diabetes. A manuscript demonstrating these findings, entitled: Type 2 Diabetes in African Immigrants Presents with Three Physiologic Subtypes and a Range of BMI from Normal to Obese: Impact on Screening and Treatment is under review at the British Medical Journal- Open Research Diabetes. Kyle Messier, NIEHS Dr. Kyle Messier’s Spatiotemporal Health Analytics Group has two overarching themes: (1) geospatial exposure, disparity, and risk mapping; and (2) Spatiotemporal mapping connections to toxicology. Development of software and manuscript to support integration of environmental exposure data into population and clinical human health studies. Example of research highlights during FY25 are 1) Continued development of the GeoTox framework and software to support geospatial risk assessment from chemical mixtures, 2)Development of a novel Bayesian methodology for multivariate outcome dose-response modeling of -omic data, 3) Continued development of reproduceable and updateable pipelines for near real time air pollution exposure predictions across the United States, and 4) Mid-Tenure BSC review in May 2025.