What We Do.
Single-Cell Lineage Tracing
We have pioneered technologies that integrate single-cell transcriptomics with permanent, heritable barcodes to trace cell fate at clonal resolution in vivo. These systems allow simultaneous recovery of a cell’s identity, molecular state, and lineage history, enabling the reconstruction of developmental trajectories and clonal dynamics across complex tissues. Our approaches are applicable to both embryonic and adult contexts, revealing how progenitor diversity, lineage commitment, and clonal competition shape tissue composition.
In addition to these high-resolution molecular maps, we are developing spatially resolved lineage tracing methods that will allow visualization of clonal architecture and niche relationships directly in intact tissues. This next generation of in situ clonal mapping will make it possible to correlate cell position, lineage history, and transcriptional state, offering unprecedented insight into how spatial organization influences tissue development, regeneration, and disease.
Hematopoiesis
Our hematopoiesis research centers on dissecting the complex processes underlying blood cell development and maintenance throughout life, from embryogenesis to aging. Historically, the hematopoietic stem cell (HSC) has been regarded as the primary source of lifelong blood production. However, using barcoding technologies, we demonstrated significant long-term contribution from other populations, including embryonic multipotent progenitors (MPPs), which play an unexpectedly robust role in blood cell generation under physiological conditions. Our studies further show that lineage commitments and intrinsic biases established early during development persist into adulthood, profoundly affecting immune function, aging, and disease susceptibility.
Beyond adult hematopoiesis, we deeply investigate developmental origins, particularly how embryonic endothelial-to-hematopoietic transitions (EHT) establish blood cell populations. By mapping the embryonic and fetal origins of specific hematopoietic lineages, including tissue-resident macrophages and lymphoid progenitors, we are providing new insights into the lineage continuity and distinct contributions of embryonic hematopoiesis. These developmental insights inform our understanding of adult hematopoietic hierarchy and identify novel therapeutic targets for hematological disorders, immune deficiencies, and aging-related dysfunction.
Our insights into immune aging—characterized by decreased lymphocyte production, impaired immune responses, and heightened cancer risk—highlight the importance of precisely defining progenitor populations responsible for maintaining immune function. Our ongoing research aims to leverage this knowledge to rejuvenate aging hematopoietic systems, enhance bone marrow transplantation efficacy, and develop targeted therapies for hematologic malignancies.
Liver Biology
Our liver research combines clonal lineage tracing, epigenomic profiling, and functional studies to understand how hepatocytes maintain identity, respond to injury, and regenerate. We have shown that hepatocyte-to-biliary reprogramming—a critical aspect of liver plasticity—is actively constrained by specific epigenetic regulators, such as histone acetyltransferases, which act as “brakes” on fate flexibility. Targeted modulation of these pathways enhances regenerative potential, opening therapeutic avenues for chronic injury, fibrosis, and congenital disorders such as Alagille syndrome.
We also study the Hippo signaling pathway, a master regulator of organ size, regeneration, and tumor suppression in the liver. Our work has defined how Hippo pathway inactivation drives hepatocyte proliferation, cell fate changes, and—under certain contexts—tumorigenesis. By integrating Hippo pathway biology with functional genomics, single-cell and in situ lineage mapping approaches, we aim to design interventions that safely harness regenerative programs and limit malignancy cell growth.