Keisuke Kaji Research Group

Biology of reprogramming

The Kaji lab is dedicated to generating cell types that are in high demand for research and therapeutic applications. Recently, the lab has focused on expanding fully functional human hepatocytes for use in toxicology testing, disease modelling, and the development of hepatocyte-based therapies

Professor Keisuke Kaji

Group Leader

Contact details

Group members

Rebecca Granskog, Research Assistant

My Linh Huynh, Postdoctoral Research Fellow

Jakob Jeriha, Martin Lee Doctoral Scholarship Student

Research interests

The generation of induced pluripotent stem (iPS) cells in 2006 demonstrated that cellular identity can be significantly altered through the forced expression of transcription factors and specific culture conditions. However, faithfully recapitulating the full functionality of most in vivo cell types from pluripotent stem cells (PSCs) remains a major challenge.

Hepatocytes are a prime example. PSC-derived hepatocytes typically remain immature even after 30 to 60 days of culture. This limitation has made the supply of fully functional hepatocytes heavily reliant on scarce donor tissue, despite high demand from pharmaceutical companies and academic researchers for toxicology testing, drug screening, and cell therapy development.

Recently, the Kaji lab developed novel culture conditions that enable human hepatocytes to be reprogrammed into proliferative precursors named as chemically expanded hepatocytes precursors (pre-cHep). These pre-cHep cells can expand over one million-fold while retaining their ability to repopulate damaged liver tissue (patent pending). Furthermore, they can be re-differentiated in vitro into mature chemically expanded hepatocytes (cHep), enabling the large-scale production of fully functional hepatocytes.

Kaji research group infographic

The lab is currently focused on refining and advancing this technology to make pre-cHep and cHep broadly applicable in both industry and academia for toxicology testing, drug screening, and cell therapy development. In parallel, the lab is utilizing pre-cHep and cHep, combined with genetic manipulation techniques, to develop advanced liver disease models.

Key projects

Refining and advancing pre-cHep and cHep culture conditions for in vitro and in vivo applications

MASLD (Metabolic dysfunction-associated steatotic liver disease) and MASH (Metabolic dysfunction-associated steatohepatitis) modelling with pre-cHep/cHep

Hepatocellular Carcinoma modelling with pre-cHep/cHep

Selected publications

 

Collaborators

Internal

Stuart Forbes

David Hay

Prakash Ramachandran

Jonathan Fallowfield

Tim Kendall

Tom Bird

External

Hiroshi Suemizu

Stephen Tsui

Biopredic

Cytotheryx

AstraZeneca

Funders

Medical Research Council