Dr. Xiao-Di Tan’s Pediatric Mucosal Inflammation and Regeneration Research Program
Pediatric Mucosal Inflammation and Regeneration Research Program (PMIR2P) Heading link
Investigators within PMIR2P are dedicated to various aspects of the pathophysiology of intestinal and liver diseases. Their pioneering studies span a wide range of disciplines aimed at understanding the intricate mechanisms underlying tissue injury pathogenesis, exploring tissue wound healing responses, and shaping novel strategies for disease prevention. Their overarching goal is to rigorously investigate the pathogenesis of intestinal and liver diseases in both adults and children, thereby advancing knowledge of therapeutic targets for treating these disorders in humans. Ongoing research within PMIR2P is supported by grants from the NIH and the U.S. Department of Veterans Affairs.
Lab Highlights Heading link
Ongoing Research Projects Heading link
Novel Mechanisms in the Pathogenesis of Necrotizing Enterocolitis (NEC)
NEC is a serious intestinal disease that primarily affects preterm infants and is a leading cause of death among premature infants in the United States. In this project, we will address fundamental questions about why and how NEC occurs in a group of high-risk premature babies upon postnatal exposure to NEC-associated environmental factors in combination with activation of antimicrobial immune responses. This work will provide a novel mouse model relevant for human NEC, advance knowledge of how the interaction between NEC risk factors and activation of the neonatal immature immune system triggers NEC development and gain mechanistic insights that will inform the development of new strategies for the prevention and treatment of NEC.
Surgical Studies of Gut Epithelial Apoptosis-initiated Critical Illness
Gut epithelial injury is associated with various severe surgical conditions. In this project, we will examine the exact role and underlying mechanisms of scattered intestinal epithelial cell apoptosis in the development and progression of critical surgical illness using a novel transgenic mice model. This project will yield a novel animal model for studying molecular mechanisms and pathophysiology of gut injury-associated critical surgical illness, provide insights about how scattered IEC apoptosis contributes to development of severe surgical conditions such as NEC and sepsis, and advance our knowledge on novel strategies for prevention of gut injury-associated critical illness in future.
Mechanisms Underlying Regulation of Intestinal Epithelial Homeostasis in Sepsis
Intestinal epithelial homeostasis is dysregulated during systemic inflammation associated with sepsis and critical surgical conditions. In this project, we will address the molecular mechanisms by which septic inflammation alters intestinal stem cells and progenitor cell proliferation, an important event for maintaining intestinal epithelial homeostasis. The proliferative cells in the intestinal crypts are composed of Lgr5-expressing crypt base columnar cells and transit amplifying cells. We will delineate the mechanism by which sepsis affects the proliferation of these cells. This work will lead to the identification of novel molecular targets and will ultimately advance strategies for restoring intestinal epithelial homeostasis in patients with sepsis and critical surgical illness.
Unraveling the Cellular and Molecular Complexities of Sepsis Pathogenesis
Sepsis is a life-threatening condition characterized by a dysregulated immune response to infection. In this project, we will focus on the post-transcriptional regulation of inflammatory mediators by microRNAs, gene regulation mechanisms during systemic inflammation, and the pathogenesis of gut-injury-related sepsis in animal models. In this study, we investigate how severe intestinal inflammation facilitate bacterial translocation and induce systemic-immune responses and gain insights for therapeutic strategies targeting systemic inflammation arising from intestinal injury and infection.
Molecular Mechanisms Underlying Hepatocyte Apoptosis-Induced Liver Wound Healing Response
Liver injury-associated diseases remain a significant public health challenge in the in the United States. In this project, we will use novel research tools to investigate molecular mechanisms underlying progression of hepatocyte apoptosis-induced liver wound healing response. This project will have the potential to markedly advance our understanding of underlying pathophysiology of liver inflammation and regeneration. It will ultimately lead to the identification of novel molecular targets and the development of new potential therapeutic agents for patients with liver disease.
Lab Members Heading link
Xiao-Di Tan, MD
Director of CPTRE
Email:
Heng-Fu (Henry) Bu, DVM & PhD
Email:
Xiao Wang, MD, PhD
Email:
Hua Geng, PhD
Email:
Saravanan Subramanian, PhD
Email:
Nazeer Hussain Khan, PhD
Email:
Qianming Jiang, PhD
Email:
Grants Heading link
- R01 DK123826 – Tan (PI)
Date : 02/15/2020 – 01/31/2024
Project : Mechanisms underlying regulation of intestinal epithelial homeostasis in sepsis - R01 DK129960 – Tan (PI)
Date : 04/01/2022 – 03/31/2026
Project : Insights into a multi-hit process in the development of necrotizing enterocolitis - R01 DK116568 – Tan (Co-Investigator)
Date : 03/01/2019 – 02/28/2024
Project : Role of the intestinal microvasculature in necrotizing enterocolitis - I01BX006085 (VA/BLR&D MERIT Review Award) – Tan (PI)
Date : 10/01/2023 – 09/30/2027
Project : Milk fat globule-EGF factor 8 and hepatocyte apoptosis-induced liver wound healing response