Jurgen Ludwig, our superb hepatopathologist, told me that “…this disease simply does not exist because I have never seen a case at autopsy”. At any rate, a serendipitous partnership with a bright and very energetic GI fellow, Russ Wiesner, led to the publication of an important

article describing the clinical, biochemical, and histologic features of patients with PSC seen at Mayo.17 With the advent of endoscopic retrograde cholangiopancreatography, which came along just at the right time for someone interested in studying PSC, and the resultant increase in its diagnosis, Russ, I, and many others at Mayo were able to generate a large series of studies that put this disease on the map,18–29 including the first randomized clinical trial in PSC.30 Thus, PSC became a well-recognized and increasingly diagnosed, Erlotinib molecular weight albeit still idiopathic, cholestatic liver disease and Mayo became a major referral center for this syndrome. I seemed to have chosen well and at the right time, clearly more a matter of luck than brilliance! While

my laboratory Ku 0059436 was still primarily focused on the pathobiology of hepatocytes, I had somewhat of an insight for reasons that, quite frankly, I don’t even remember. I hypothesized that the epithelial cells that lined the biliary tree were likely the target cells for many of the cholestatic liver diseases (PBC, PSC, cholangiocarcinoma, etc.) that were increasingly being

seen in our clinics. Indeed, I had tucked away in my “idea file” years earlier that a future area for fruitful exploration might be understanding the biology of the cells that lined the biliary tree (we subsequently coined the term “cholangiocyte” for these cells at the first American Association for the Study of Liver Diseases [AASLD] Single Topic Conference on selleck inhibitor the Pathobiology of Biliary Epithelia that I coorganized with Al Sirica in 2000). The working hypothesis was, and still is, that a group of diseases, which we termed the “cholangiopathies”,31 could be conceptually clustered despite different etiologies, because their common final pathway was alteration in the phenotype of the cells that lined the biliary tree, i.e., the cholangiocytes (Table 1). The problem at the time, however, was that there were essentially no techniques available to study cholangiocytes. So, because scientific advances require techniques to answer questions and test hypotheses (a principle that de Duve often emphasized), I devoted a substantial amount of time and effort developing methodologies to investigate cholangiocyte biology (Fig. 3A),32–40 including an animal model of immune-mediated cholangitis.