Chronic pancreatitis and cystic fibrosis. Our group is interested in the mechanism by which Cystic Fibrosis (CF) gene mutations lead to the phenotypic expression of disease. We have discovered that this involves alterations in fatty acid metabolism. Correction by high doses of docosahexaenoic acid in a mouse knockout model of CF reverses the pathology. Studies are underway in humans in CF and CF related diseases such as Primary Sclerosing Cholangitis and Pancreatitis.
In addition, in collaboration with Alvaro Pascual-Leone MD, PhD in neurology, we have discovered that site within the brain (cortical SII) that modulates visceral pain sensation in patients with chronic pancreatitis. In an NIH funded study, we have shown that pain is attenuated in response to a 10 day course of repetitive Transcranial Magnetic Stimulation.
Sheth S, Shea J, Bishop MD, Chopra S, Regan MM, Malmberg E, Walker C, Ricci R, Tsui L-C, Durie PR, Zielenski Z, and Freedman SD. Association of Primary Sclerosing Cholangitis with Mutations of the Cystic Fibrosis Gene. Human Genetics 2003, 113:286-292.
Freedman SD, Blanco PG, Zaman MM, Shea J, Ollero M, Hopper IK, Weed DA, Gelrud A, Regan MM, Laposata M, Alvarez JG, and O?Sullivan BP. Association of Cystic Fibrosis With Abnormalities In Fatty Acid Metabolism. New Engl. J. Med, 2004; 350:560-569.121:950-957.
Freedman SD, Katz MH, Parker EM, Laposata M, Urman MY, and Alvarez JG. A membrane
lipid imbalance plays a role in the phenotypic expression of cystic fibrosis in cftr-/- mice. Proc. Natl. Acad. Sci. 1999, 96:13995-14000.
Blanco, PG, Zaman MM, Junaidi O, Sheth S, Yantiss R, Nasser I, and Freedman SD. Induction of colitis in cftr-/- mice results in bile duct injury. Am. J. Physiol. Gastrointest Liver Physiol, 2004, 287: G491-496.
Andersson C, Al-Turkmani MR, Savaille JE, Alturkmani R, Katrangi W, Cluette-Brown JE, Zaman MM, Laposata M, Freedman SD. Cell culture models demonstrate that CFTR dysfunction leads to defective fatty acid composition and metabolism. J Lipid Res. 2008; 49(8):1692-700.
External Recognition:
Recipient of the American Gastroenterological Association Industry Scholar Award
1999 North American Cystic Fibrosis Foundation Plenary Speech
Co-Director, Havard Clinical/Translational Science Center (Associate Dean for Clinical and Translational Research)
NIH grant council
Cystic Fibrosis Grant council
Canadian Cystic Fibrosis Grant council
1996 Patent granted on 7/29/97 on design and implementation of a modified secretin pancreatic function test (Patent# 5651769).
1998 Patent granted on 1/30/2001 (US patent # 6.180.671) on a novel lipid formulation for the treatment of conditions related to imbalances in Docosahexaenoic and Arachidonic Acid.
Major Collaborative Activities:
Nid Afdhal at BIDMC
Lap-Chee Tsui/Peter Durie at the Hospital for Sick Children in Toronto
Brian O'Sullivan, UMASS Medical Center
Alvaro Pascual-Leone at BIDMC
