Hongbing Liu, PhD

The regulation of kidney development by Histone Deacetylases

The kidney is one of the best characterized organ systems in developmental biology and serves as an outstanding model for studying organogenesis. Each human kidney contains approximately 200,000 to 1.8 million nephrons — the functional units responsible for waste elimination, volume and electrolyte regulation, blood pressure control, and bone mineral homeostasis. Because nephrons are terminally differentiated and lack meaningful regenerative capacity, the nephron complement established at the completion of nephrogenesis defines the kidney's functional reserve for life, and its reduction predisposes individuals to progressive kidney disease, hypertension, and cardiovascular complications. The long-term goal of my research program is to elucidate epigenetic mechanisms, with particular emphasis on histone acetylation and deacetylation, that regulate nephron progenitor cell (NPC) fate decisions and how their dysregulation contributes to developmental abnormalities, tumorigenesis, and chronic kidney disease (CKD). To this end, my laboratory pursues three integrated research directions: (1) defining the cell-type–specific roles of histone deacetylases (HDACs) in NPC self-renewal, differentiation, and stromal-epithelial crosstalk during nephrogenesis; (2) investigating how HDAC-dependent epigenetic mechanisms drive Wilms tumor initiation and progression, with the goal of identifying novel therapeutic vulnerabilities in this common pediatric kidney malignancy; and (3) determining how adverse intrauterine environments, modeled through maternal protein restriction–induced intrauterine growth restriction, reprogram histone modification landscapes in the developing kidney, thereby programming lifelong CKD susceptibility within the Developmental Origins of Health and Disease (DOHaD) framework. Together, these studies aim to define the epigenetic logic of renal development and disease, and to translate these insights into preventive and therapeutic strategies targeting chromatin-modifying enzymes in kidney and renal–cardiovascular disorders.