Bio: Dr. Fondufe-Mittendorf is a professor in the Department of Epigenetics and serves as the Chair of Cell Biology at the Van Andel Institute in Michigan. Since 2011, she has led an independent research program focusing on the intersection of chromatin biology, RNA biology, environmental toxicology, and cancer. Her lab examines how environmental toxicants contribute to disease development. Despite the disconnect between chromatin biology and toxicology, her work has provided fundamental insights into epigenetic gene regulation, chromatin architecture, and oncogenesis over the past 11 years, especially concerning disease pathogenesis influenced by heavy metals. Her primary goal is to decipher chromatin-mediated responses to environmental signals to aid in the development of preventive and therapeutic strategies against diseases caused by widespread pollutants and toxic substances. Supported by multiple NIH grants and a National Science Foundation grant, her lab has received significant recognition through publications and prestigious awards, including the NIH-Maciag Award and features on prominent scientific platforms.

Abstract: Proper gene regulation is crucial for normal development, while its dysregulation is linked to diseases like cancer. Eukaryotic DNA is organized as chromatin, influencing gene expression. Inorganic arsenic (iAs) affects gene regulation by altering the epigenome. Recent research has mapped the 2D epigenetic landscape influenced by iAs, showing that its effects on gene activity could stem from both local and distant epigenetic changes. Beyond this, the 3D chromatin structure plays a dominant role in gene expression. CTCF, the “master weaver” of the genome, and special AT-rich binding proteins (SATB) regulate this 3D organization. Disruption of these proteins alters chromatin structure and nuclear interactions, leading to gene dysregulation. Our studies reveal that iAs inhibits CTCF binding, potentially rewiring the genome toward an oncogenic state. In addition, iAs dysregulates the nuclear architecture by ectopically enhancing the expression of SATB2. Dysregulation of SATB2 occurs also at the splicing level, where a circular RNA from SATB2 is generated and prevents SATB2 from anchoring chromatin to the nuclear membrane. These disruptions contribute to spatial genome reorganization and oncogenic gene expression. Understanding these mechanisms will help clarify how iAs exposure leads to 3D chromatin changes and nuclear matrix interactions, providing insights into its role in cancer development.