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The projects in the group all have a single common feature in that they all started as a problem in a patient. Furthermore the projects attempt to delineate a fundamental biological process derived from an observation in patients then explored in the laboratory. I am also interested in testing hypotheses in clinical situations which can be translated into laboratory projects. This is in many ways better than a model, it is an authentic, direct study of the relevant biology.
There are currently two groups of projects. The first entails the elucidation of the mechanisms underlying the development of non-cirrhotic portal hypertension, particularly in the setting of systemic diseases such as Chronic Granulomatous Disease, Sickle Cell Disease, Turner Syndrome, and Congenital Hepatic Fibrosis. Clinical databases linked to tissue and serum samples have been developed and research has focused on defining the clinical syndromes and developing mechanistic insights in the laboratory, in particular utilizing liver biopsies to do so. These projects have implications not only for the diseases themselves but also serve as a model for portal hypertension and thus have relevance for all end stage liver disease. This work could not be done without significant collaboration with the relevant clinical groups.
The second group of projects explores viral hepatitis for disease insights, especially in acute hepatitis C and hepatitis D. Here again clinical databases (related to treatment trials) have been established with related serum and liver samples. These in turn have been utilized to study problems such as the evolution of acute hepatitis C and viral breakthrough on treatment.