Unlocking cellular secrets: Innovations driving research in liver disease & cancer

Liver diseases, particularly chronic liver conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic-associated steatohepatitis (MASH), as well as liver fibrosis and liver cirrhosis present serious global health challenges, causing millions of deaths. These diseases often progress silently, making early detection difficult and limiting treatment options. Additionally, liver cancer and prostate cancer are among the most common and deadly cancers in men due to late diagnosis and cancer metastasis. With the rising incidence of chronic liver diseases, lack of treatment options, and high mortality rates, there is an urgent need for:

i. Improved understanding of disease mechanisms to identify novel therapeutic targets.
ii. Discovery of biomarkers for early disease detection and identifying at-risk patients.
iii. The development of safe and effective treatment strategies.

Therefore, this thesis underscored the importance of unlocking cellular secrets in advancing disease understanding, developing early diagnostic tools, and exploring novel therapeutic strategies to tackle the growing burden of chronic liver diseases and cancer. This thesis contributed to this goal by:

i. Enhancing MASLD disease understanding by developing a method for single cell secretion analysis of HSCs;
ii. Adapting this method to evaluate macrophage subpopulations in MASH, identifying proinflammatory LAMS as potential therapeutic targets;
iii. Exploring cellular differences between male and female immune cells in MASLD;
iv. Advancing early diagnosis and prognosis of prostate cancer by identifying and isolating cCAFs as potential biomarkers for metastasis or treatment resistance;
v. Developing the Mag-Click-Release system as a novel approach for isolating EVs as early liver cancer biomarkers;
vi. Exploring the AXT-LPA pathway as a promising therapeutic target for the treatment of chronic liver diseases;
vii. Establishing the novel ATX inhibitor Cpd17 as a promising therapeutic treatment for acute liver injury and pathological MASH in mice.
The findings presented herein lay the groundwork for future research that integrates cellular biology, diagnostic innovations, and targeted therapies to improve patient outcomes in these complex conditions.