research
Cell identity is a dynamic property that can be acquired or lost as cells interact with their environment. This dynamic cell plasticity plays a crucial role in maintaining tissue homeostasis, facilitating regeneration, and driving disease progression. The Sun lab is dedicated to unraveling the intricate mechanisms underlying the shaping of cell identity and how these processes contribute to the adaptation or promotion of physiological and pathological processes. Through our research efforts, we seek to gain deeper insights into the fundamental principles governing cell identity dynamics, with the ultimate goal of developing innovative strategies for therapeutic intervention in various disease states.
Mechanisms of Liver Regeneration
The liver stands as the sole organ in our body capable of complete regeneration. This remarkable ability hinges upon precisely orchestrated processes involving injury sensing, diverse injury response mechanisms, and tightly regulated initiation and termination of regeneration. These mechanisms ensure the restoration of liver function while mitigating the risk of tumor formation.
In our laboratory, our focus lies in elucidating how the liver responds to various types of injuries and unraveling the intricate mechanisms governing liver regeneration at both spatial and single-cell levels. By delving into the molecular intricacies of liver regeneration using mouse models, we aim to uncover novel targets that hold potential for regenerative therapeutics. Our long-term objective is to contribute to the development of innovative regenerative therapies by leveraging our understanding of liver regeneration mechanisms.
Regeneration and Chronic Liver Diseases
The liver possesses unparalleled regenerative capabilities; however, these abilities are compromised in the context of chronic injuries such as Metabolic Associated Steatohepatitis (MASH) and fibrosis. The interplay between multicellular dynamics at the interface of regeneration and chronic injury presents a unique avenue for understanding these diseases. Passive and active regeneration hold promise as potential strategies against chronic liver injuries.
Our objective is to elucidate the key genes and signaling pathways involved in the regeneration-induced recovery of chronic liver diseases using organoids, single-cell multiomics techniques coupled with validation in mouse models. By comprehensively dissecting the molecular landscape underlying liver regeneration and its modulation in the context of chronic injury, we aim to identify novel therapeutic targets capable of promoting disease regression without promoting tumorigenesis. This research endeavor seeks to provide valuable insights into the pathogenesis of chronic liver diseases and offer potential avenues for therapeutic intervention.
Design Principles of Liver Zonation
Tissue zonation refers to the phenomenon wherein cells undergo changes in molecular identity based on their spatial localization within an organ, as observed in organs such as the liver, pancreas, and gut. The liver, in particular, plays a pivotal role in numerous metabolic processes essential for maintaining overall bodily homeostasis. To efficiently execute these functions, different metabolic pathways within the liver are spatially separated along the liver porto-central axis. This segregation minimizes the futile cycling of substrates or energy, ensuring optimal metabolic efficiency. This specialized functional arrangement, known as liver metabolic zonation, is integral for energy metabolism and xenobiotic detoxification.
However, disruption of this zonation is commonly observed in metabolic liver diseases and liver cancer, underscoring its significance in liver pathophysiology. By combining multiomics and genetic models, our objective is to elucidate the underlying design principles governing liver zonation and its implications in conditions such as metabolic dysfunction-associated steatohepatitis (MASH) and liver cancer. By unraveling the intricacies of liver zonation, we aim to gain valuable insights into the pathogenesis of these diseases and identify potential therapeutic targets.