I am Zhicong Zhao, a clinician-scientist at Renji Hospital, Shanghai Jiao Tong University School of Medicine. My research focuses on addressing the critical challenge of low long-term survival rates after liver transplantation, particularly the mechanisms of chronic graft dysfunction. I investigate the “stress-epigenetic interaction mechanisms” that contribute to transplant failure, with a goal to uncover novel insights that could lead to improved outcomes. My research is aligned with the national strategic needs for advancing organ transplantation and improving patient survival. Over the past five years, I have published 19 SCI papers, including seven as the first or corresponding author in top-tier journals such as Cell.
I am excited to apply for the 2025 Hong Kong Laureate Forum as it provides a unique opportunity to interact with world-renowned scientists and researchers in the field of transplantation and epigenetics. This forum will allow me to gain insights into the latest breakthroughs, share my own work, and engage in meaningful discussions that could shape the future of organ transplantation. I believe that participating in this forum will not only enrich my research but also foster international collaborations that are essential for addressing the complex challenges of liver transplantation.

Liver transplantation is the most effective treatment for end-stage liver disease, but the global shortage of donor livers remains a major challenge. Xenotransplantation, particularly liver xenotransplantation, offers a promising solution, yet faces significant barriers due to the liver’s complex anatomy and physiology. Unlike heart or kidney transplants, pig livers cannot fully substitute human liver function. To address this, our research focuses on generating humanized livers within xenogeneic hosts through advanced gene editing and organ reconstruction techniques. We aim to uncover the epigenetic mechanisms governing the “stress-epigenetic interaction” during xenogeneic transplantation, enabling efficient human hepatocyte engraftment and regeneration.

Using immunodeficient animal models and human primary hepatocyte transplantation, we employ single-cell transcriptomics, ATAC-seq, and CRISPR-Cas9 screening to investigate cell fate decisions, epigenetic remodeling, and microenvironmental adaptation. Our goals include: 1) decoding the stress-responsive epigenetic regulation of human hepatocytes in xenogeneic environments, 2) identifying intercellular communication between human and host cells, and 3) screening genes and small molecules to enhance engraftment and functionality. Ultimately, we aim to achieve scalable in vivo regeneration of functional humanized livers, laying a scientific foundation for future clinical translation of liver xenotransplantation.