Dr. Steven Freedman, the Chief of the Division of Translational Research and Professor of Medicine at Harvard Medical School. He is Director of The Pancreas Center and is a worldwide leading expert on pancreatic disease and Cystic Fibrosis.
Dr. Freedman's laboratory is translationally based with strong basic science and clinical research components. The two areas of focus are determination of 1) the mechanism(s) of inflammation in Cystic Fibrosis and chronic pancreatitis and 2) the mechanism and treatment of refractory visceral pain in these diseases.
Understanding the Mechanism by which Cystic Fibrosis Gene Mutations Lead to Disease
Genetic studies conducted by Dr. Freedman and his research team have shown that 50% of patients with idiopathic chronic pancreatitis have mutations in the cystic fibrosis (CFTR) gene. To understand how these mutations lead to the phenotypic expression of disease, his group has demonstrated that CFTR dysfunction leads to a defect in fatty acid metabolism in CF affected organs using transgenic mouse strategies. Correction of this abnormality reversed the pathologic changes in the pancreas, ileum, as well as Pseudomonas induced lung inflammation. The same fatty acid defect was confirmed in humans with CF, demonstrated a CFTR gene dosing effect, and has led to the first clinical trial. Current projects include defining the mechanism by which CFTR dysfunction directly alters fatty acid biosynthetic enzymes, the role of PPAR's in this process, and the identification of modifier genes.
Cortical Dysfunction as the Mechanism for Refractory Visceral Pain
The other focus of Dr. Freedman's lab is on visceral pain mechanisms and the development of novel treatment strategies. In collaboration with Alvaro Pascual-Leone MD, PhD, their groups have identified the site within the brain representing pain from chronic pancreatitis. They have hypothesized that this region, referred to as SII in the right side of the brain, is dysregulated in chronic abdominal pain syndromes such as chronic pancreatitis and results in refractory pain. They have demonstrated that inhibition of SII using Transcranial Magnetic Stimulation (TMS) reduces pain and appears to regulate the release of inflammatory mediators targeted to the pancreas. Current projects include: an NIH funded double-blind, sham controlled trial of TMS in the treatment of refractory abdominal visceral pain and its effect on modulation of cytokine and chemokine responses; identification of the neurotransmitters responsible for pain perception in SII using MR Spectroscopy and its modulation by TMS; and identification of cortical pathways leading to the regulation of the innate immune response through activation of SII.