Grant Number:	5R00CA267674-05 Interpret this number
Primary Investigator:	Miller-Kleinhenz, Jasmine
Organization:	University Of Mississippi Med Ctr
Project Title:	Investigating Socio-Structural Determinants of Health and the Tumor Epigenome to Understand the Etiology of Racial Disparities in Breast Cancer
Fiscal Year:	2026

The overarching goal of this project is to examine how socio-structural determinants of health impact the breast tumor DNA methylome, activation of oncogenic signaling, and ultimately, the disparate development of triple-negative breast cancer (TNBC) in different populations. The etiologic basis of demographic differences in TNBC is not well understood and few studies have investigated the impact of social determinants of health as potential drivers of these differences. Recent work from the McCullough group shows that, in Atlanta, Black women with breast cancer are more likely to live in redlined neighborhoods than White women (80% vs 20%) and that living in areas with high rates of redlining is associated with a 60% increase in breast cancer mortality. These data support the need to investigate redlining as an etiologic driver of demographic differences in TNBC. We posit that to achieve optimal health for everyone, it is necessary to understand how socio-structural differences can be adversely manifested biologically, resulting in breast cancer. The goal of this study is to elucidate a biological mechanism that explains the association between neighborhood-level redlining and differences in TNBC. This investigation requires a researcher with a diverse skillset that can address questions from the population to the bench. This Pathway to Independence Award (K99/R00) application by Dr. Miller-Kleinhenz intends to uniquely position her to answer these questions by building on her prior expertise in breast tumor biology and expanding her skill set in social and molecular epidemiology and epigenetics. To achieve the aims of this research, Dr. Miller-Kleinhenz will focus her training in three areas, (1) increasing knowledge through a comprehensive didactic curriculum, (2) experiencing and learning from varied research environments, and (3) fostering professional development through leadership, scientific communication, and then transitioning to independence. These training goals will be supervised by an interdisciplinary mentoring team, led by Dr. Lauren McCullough, a cancer and molecular epidemiology expert and an Assistant Professor of Epidemiology at Rollins School of Public Health at Emory University. The co-mentor will be Dr. Adam Marcus, an expert cancer biologist and a Professor of Hematology and Oncology, and the Interim Executive Director of the Winship Cancer Institute. This training will aid Dr. Miller-Kleinhenz in pursuing the following aims during the K99 phase: Understanding the impact of redlining as a social-structural determinant of health that is associated with TNBC development (Aim 1) and examining redlining-associated DNA methylation signatures of the breast tumor epigenome in TNBC (Aim 2). During the R00 phase, she will determine the pathobiological significance of redlining-associated expression of oncogenic signaling pathways in TNBC (Aim 3). This 5-year research and training plan will allow Dr. Miller-Kleinhenz to establish an independent research program that will elucidate new avenues for policy interventions and pharmacological treatments that would contribute to the ultimate goal of reducing differences in cancer health outcomes.