Welcome! The laboratory of Jonathan Dranoff is located in the BioMed II building at UAMS. Visitors and new collaborators are always welcome. Our research goals are twofold, divided into two distinct, but interrelated projects, both funded by NIH/NIDDK external funds.
Pathogenesis of Biliary Fibrosis & Cirrhosis: Biliary cirrhosis is a distinct condition at the clinical and pathological level, and we propose that it is mediated by a distinct pathophysiological mechanism. Specifically, we propose that biliary cirrhosis occurs in response to dysregulated intercellular communication between bile duct epithelia and portal fibroblasts. Our work in this area has led us to investigate a variety of targets, including purinoceptors, ecto-nucleotidases, the cytokine IL-6, and the chemokine CCL2/MCP-1. It is our sincere hope that our work leads to novel treatments to prevent or reverse biliary cirrhosis, which is the cause of the majority of pediatric liver failure and approximately 20% of adult liver failure.
IMAGE: Co-culture of bile duct-derived cells (labeled with MCL-1) and primary rat portal fibroblasts (labeled with vimentin) visualized by confocal immunofluorescence. Nuclei are labeled with TOPRO (from Jhandier MN, J. Biol. Chem. 2005).
Purinergic Signals & Downstream Intracellular Calcium Signals in Hepatic Stellate Cells (HSC): HSC are critical mediators of scar formation in the liver and are regulated by a variety of hormones acting via intracellular calcium. We have found evidence that calcium signals have distinct effects on HSC function, depending on where in the cell the signal originates. We propose that nuclear effects of calcium in HSC are mediated by and result in physiological effects that are quite different from effects of calcium in dendrite-like cell extensions. We believe that this work may lead to new approaches to the prevention and/or treatment of cirrhosis, which are in desperate clinical need.
IMAGE: Confocal immunofluorescence to demonstrate the expression of the Type I inositol triphosphate receptor (IP3R) in myofibroblastic rat HSC. The Type I IP3R is expressed in nuclei and dendrite-like cell extensions, where it co-localizes with the ER marker calreticulin (from Kruglov EA, Am. J. Physiol. 2007).