Towards understanding of cell-to-cell communication in liver pathogenesis

My long-term goal is to understand age-associated diseases for their cure. Diseases such as cancers, fibrosis, diabetes and cardiovascular diseases become more serious problems as the average life expectancy increases globally. Their occurrence is closely related to chronic inflammation, in which various cell types cooperatively contribute to their progression. To fully understand such complex phenomena, we need systematic approaches. I studied mechanism of cell death in multiple cell lines towards chemotherapy using both experimental and computational approaches during my PhD (See Biography). For my postdoc, I was determined to work on more realistic model systems of diseases, particularly in the liver, and embrace the complexity of the real organ. Chronic diseases caused by losing the control of inflammation, often initiated by necrotic cell death, are much less explored, and just as medically important as cancer research.  Both holistic and detailed understanding of different models will be important to understand the pathology development clearly.

Withdrawal of post-marketed drugs remains a challenge in pharmaceutical industries. Drug-induced liver injury (DILI) is one of the most frequent causes of such withdrawal. Mechanisms of DILI and consequent development of chronic liver pathology have been studied at both molecular and histologic levels in rodent models. However, several cell types communicate with each other to cooperatively develop a pathological state of the tissue over time, and it is still challenging to understand its complete picture of chronic liver pathology. The goal of my project is to understand the essential cell-to-cell communication in chronic liver pathology induced by multiple drugs. Emergent technology, single-cell RNA-seq developed at Harvard Medical School, will let us gain a much deeper picture, where signaling is resolved at the single cell level. I am investigating the progression of pathologies in both in vivo mouse and in vitro liver spheroid models. The progression of pathologies seen in these DILI models is reminiscent of chronic liver diseases in human.