Dr. Hongbing Liu's Lab

The kidney plays a fundamental role in maintaining systemic physiological homeostasis. Proper mammalian kidney development is essential for the elimination of nitrogenous waste, regulation of blood volume and electrolyte balance, control of blood pressure, and maintenance of bone mineral density. The nephron is the functional unit of the kidney, and each human kidney contains approximately 200,000 to 1.8 million highly organized and functionally specialized nephrons. Reduced nephron endowment and the resulting decline in functional renal mass predispose individuals to progressive kidney disease and cardiovascular complications, particularly hypertension.

The kidney is one of the best-characterized organ systems in developmental biology and serves as an outstanding model for studying organogenesis. Nephrogenesis, the process of nephron formation—is especially critical, as many congenital abnormalities and drug-induced injuries occur during this defined developmental window.

The long-term goal of my research program is to elucidate the epigenetic mechanisms that regulate kidney development and disease, with particular emphasis on histone acetylation and deacetylation. Our work seeks to define how chromatin-modifying enzymes orchestrate nephron progenitor fate decisions and how their dysregulation contributes to developmental abnormalities, tumorigenesis, and chronic kidney disease. Ultimately, these studies aim to inform novel preventive and therapeutic strategies targeting epigenetic modifiers in kidney and renal–cardiovascular diseases.

Ongoing Research Projects

1. Regulation of Renal Development by Histone Deacetylases

We investigate how histone acetylation dynamics control nephron progenitor cell (NPC) self-renewal and differentiation. Histone deacetylases (HDACs) are critical epigenetic regulators that remove acetyl groups from histone and non-histone proteins. In addition to modulating chromatin accessibility and transcriptional activity, HDACs regulate diverse cellular processes, including proliferation, lineage specification, and stress adaptation.

Using genetic mouse models combined with biochemical, cellular, and molecular approaches, we define the cell-type–specific roles of HDACs during nephrogenesis. Beyond NPCs, we also examine HDAC function in renal stromal progenitors, a distinct kidney lineage marked by expression of the transcription factor Foxd1. Stromal cells not only populate the interstitial compartment but also provide essential paracrine cues that regulate nephron patterning and differentiation. Our recent work has uncovered a previously unrecognized non–cell-autonomous role of stromal HDACs in controlling nephrogenesis, revealing an additional layer of epigenetic regulation in kidney development.

2. Roles of Histone Deacetylases in Wilms Tumor

Wilms tumor (WT) is the most common pediatric kidney cancer, accounting for approximately 7% of childhood malignancies. WT is an embryonal tumor believed to arise from nephron progenitor cells that fail to undergo proper differentiation. Genome-wide analyses have demonstrated a close molecular relationship between developing human NPCs and WT oncogenesis, supporting the developmental origin of this malignancy.

Although survival rates are excellent in developed countries, children with bilateral, relapsed, or high-risk disease continue to face significant therapeutic challenges and treatment-related morbidity. A deeper understanding of the epigenetic mechanisms driving tumor initiation and progression is therefore urgently needed to reduce treatment burden while preserving high cure rates.

Targeting epigenetic modifiers represents a promising therapeutic strategy in WT. Our laboratory investigates how HDACs and related chromatin regulators contribute to WT tumorigenesis, with the goal of identifying novel epigenetic vulnerabilities that may be exploited therapeutically.

3. Epigenetic Reprogramming in Chronic Kidney Disease (CKD)

Chronic kidney disease (CKD) represents a major global health burden, affecting approximately 10–15% of adults worldwide and contributing substantially to morbidity, premature mortality, and escalating healthcare expenditures. While traditionally viewed as a disease of adulthood, accumulating evidence indicates that CKD susceptibility is frequently established much earlier in life. Impaired nephron endowment has emerged as a central determinant of lifelong renal vulnerability, highlighting kidney development as a critical window of risk.

Because nephrons are terminally differentiated structures with minimal regenerative capacity, the nephron complement established at the completion of nephrogenesis defines the kidney’s functional reserve for life. This reserve is finite and progressively declines with aging and cumulative exposure to metabolic, hemodynamic, and environmental stressors. Individuals born with suboptimal nephron number therefore face increased risk of hypertension, compensatory glomerular hyperfiltration, and progressive parenchymal injury.

These observations align with the Developmental Origins of Health and Disease (DOHaD) framework, which posits that adverse intrauterine and early postnatal environments program long-term disease susceptibility. We focus on defining the epigenetic mechanisms underlying renal developmental programming. Using a well-established intrauterine growth restriction (IUGR) mouse model induced by maternal protein restriction, we investigate how early-life nutritional stress alters histone modification landscapes in the developing kidney.

We are testing the central hypothesis that fetal undernutrition reprograms renal development through aberrant activation of HDACs and related epigenetic modifiers, thereby predisposing offspring to chronic kidney disease, hypertension, and accelerated aging. Read More