Don C. Rockey, M.D.

Professor
Department: Medicine
Programs: Cell Injury, Inflammation, Fibrosis, End Organ Disease

 

 

Research Interests:

I have been fundamentally committed to scientific discovery throughout my career.  My training has been in basic, translational, and clinical research, and I have been actively engaged in all 3 areas consistently throughout.  As a physician scientist, I have remained extremely active in the full tripartite academic mission, and as such have made a commitment to remain active in basic science, translation, and clinical research.   

My basic research has focused on discovering new pathways important in patients with liver disease, particularly focused on translating findings from the bench to the clinic.  We study two primary basic research areas including (1) basic mechanisms of liver fibrosis and (2) the molecular basis of portal hypertension. We have made a number of seminal discoveries and contributions to the fibrosis field, including the discovery that hepatic stellate cells transition to hepatic myofibroblasts during liver injury and the wound healing process, that they express abundant smooth muscle proteins and function as contractile cells in the injured liver.  Further, our laboratory has single handedly identified multiple targets in liver fibrosis that have been translated to specific clinical trials (2 large randomized clinical trials) designed to test them as novel therapeutics.  The second major focus of our work in the field of molecular portal hypertension, a field that our laboratory has helped create.  This work has centered around the postulate that portal hypertension is caused not only by fibrogenesis in the liver, associated with typical structural changes (as highlighted above), but also specifically that endothelial dysfunction (i.e. an endothelialopathy) contributes to the increased intrahepatic resistance typical of most forms of portal hypertension.  This endothelialopathy is dynamic, involving remarkable cellular and molecular changes in stellate cells and in sinusoidal endothelial cells (SECs).  The work in portal hypertension has focused on the finding that nitric oxide (NO) production by SECs in the injured liver is dysregulated as a result of a series of post-translational abnormalities involving endothelial cell nitric oxide synthase (eNOS), the enzyme that synthesizes NO. The work also has a distinct mechanistic focus, specifically in the area of intracellular signaling, including novel protein-protein interactions. In all, our laboratory’s basic research has been supported by the National Institutes of Health for over 25 years now. 

I have also been highly active in clinical investigation focused around establishing management strategies for common gastrointestinal and liver diseases.  There are three major areas of focus, including the following: (1) Gastrointestinal bleeding - particularly on the usage of endoscopy) and portal hypertensive bleeding, but also upper and lower GI bleeding, and occult and chronic gastrointestinal bleeding.  Our work has led to a number of best practices in this area, in particular establishing the standard of care approach for gastrointestinal evaluation and management of iron deficiency anemia; (2) Complications of advanced fibrosis and cirrhosis (hepatic encephalopathy, ascites, hepatic hydrothorax, variceal hemorrhage, etc…).  Our emphasis has been in particular on clinical outcomes, and more importantly, on interventions and approaches that lead to changes in clinical practice on a national level.  We have recently developed a novel staging system to assess prognosis in patients with cirrhosis, and have developed prognostication tools for patients with cirrhosis and gastrointestinal bleeding; (3) Drug induced liver injury - I have been involved with the Drug Induced Liver Injury Network (DILIN) - specifically focused on helping the network establish guidelines for DILI causality assessment.  Here we have established that the best causality assessment approach appears to be structured expert opinion - and we are now working on a novel and more effective causality assessment tool.

Publications:

PubMed Collection