Characterising monocytes in autoimmune hepatitis and drug induced liver injury
Project Summary: Drug-induced liver injury (DILI) is an unpredictable, serious adverse effect occurring occasionally in response to taking common medications or dietary supplements. Although rare, its severity and potential consequences such as liver failure and death makes it an important issue during drug-development as well as in clinical practice. However, DILI can be initially indistinguishable from other liver diseases and it is impossible to predict whether an individual will develop severe effects.
Using mass cytometry we have identified that monocytes provide a way of distinguishing between drug-induced liver injury and autoimmune hepatitis. These differences a) could provide a useful clinical test to distinguish these conditions when they present clinically, and b) could provide useful mechanistic insight into how drug-induced liver injury develops compared to an autoimmune condition.
The next step in this work will be using flow cytometry to characterise these monocytes in detail, using both cell surface and intracellular staining. Specifically we are interested in monocyte characteristics such as expression of chemokine receptor type 2 (CCR2), which give monocytes "tissue homing" characteristics and enables them to migrate to the liver.
Full training will be provided in developing a flow cytometry panel, staining cells and analysing the resulting data. Our lab has a wide range of frozen PBMC from different immune-mediated liver diseases already stored, enabling experimental work to start immediately. Depending on the wishes of the student the project can be tailored more towards lab-based research or towards bioinformatics analysis of mass cytometry data.
The aim of this project will be to use the above tools to begin to address the question of why monocyte function is so different in drug-induced liver injury. The student will be part of a busy, diverse translational research lab made up of clinicians, researchers and PhD students, and this work will feed in to a number of ongoing projects we are running on immune-mediated liver conditions.
Training: Full training in PBMC isolation, cell staining and flow cytometry will be provided. An introduction to R and Python can also be provided depending on the wishes of the student.