Breann Brown, Ph.D.
Assistant Professor, Biochemistry
Structural biology & protein assembly
Research Keywords: Mitochondria, heme; enzymology; erythropoiesis; aminolevulinic acid; pyridoxal 5-phosphate; protein structure and function; protein-protein interactions
Research Specialty: Molecular Regulation of Heme Biosynthesis and Mitochondrial Metabolism
Research Description: Metabolism is not a static series of reactions—it is a dynamic, highly coordinated system driven by adaptable protein machines. The Brown laboratory investigates how protein structure, enzymology, and molecular interactions govern mitochondrial metabolism, with a central focus on heme biosynthesis. We study how enzymes function as dynamic systems regulated by allostery, ligand binding, and protein–protein interactions, rather than as static entities. Disruptions in these regulatory mechanisms contribute to a range of diseases, including anemia, cancer, and metabolic disorders.
A major area of focus is aminolevulinic acid synthase (ALAS), a pyridoxal 5′-phosphate (PLP)-dependent enzyme that catalyzes the first and rate-limiting step in heme production. We explore how enzyme inhibition, heme regulatory motifs, and protein conformational changes influence ALAS activity and erythropoiesis. Through this work, we aim to uncover fundamental principles linking protein structure and function to metabolic control.
Our research also seeks to redefine classical views of metabolism by studying “metabolons”—dynamic, multi-enzyme assemblies that coordinate metabolic pathways in space and time. By integrating structural biology, protein engineering, biophysics, enzymology, in silico modeling, and cell-based approaches, we examine how these assemblies form, adapt, and regulate metabolic flux in response to cellular cues.
Ultimately, our goal is to elucidate the molecular mechanisms that control heme metabolism and mitochondrial function, providing a foundation for developing new therapeutic strategies targeting diseases associated with metabolic dysregulation.