2009 DOM Annual Report - Department of Medicine - University of ...

Department of MedicineHIGH IMPACT PUBLICATIONSDr. Ridgway and colleagues (Diabetes 56:186-196, 2007) demonstrated that treatment of nonobese diabetic (NOD) mice, an animal model ofspontaneous Type one diabetes (T1D), with an agonist anti-CD137 antibody prevented diabetes. The mechanism of protection was specificallymediated by CD4+CD25+CD137+ T regulatory cells. This research is important because candidate genes in NOD diabetes have often been foundin human diabetes.Dr. Ascherman and colleagues (Journal of Autoimmunity 29:174-186, 2007) continue to study the role of Jo-1 directed B and T cell responsesin different genetic backgrounds of animal models (C57BL/6 and NOD congenic mice). This animal model of myositis provides a uniqueopportunity for elucidating the mechanisms of this immune-mediated muscle disease.Dr. Wasko and colleagues (JAMA 298:187-193, 2007) reported from a study evaluating patients with rheumatoid arthritis the role ofhydroxychloroquine in preventing or reducing the risk of diabetes. These finding provide the framework for defining additional mechanisms ofaction of this commonly used arthritis medication.A major research focus in the Lupus Center of Excellence is the dramatic 50-fold increased risk of myocardial infarction observed in youngwomen with lupus. Research progress in this field has been hampered by the lack of an informative animal model that can be used tounderstand the mechanisms of this process and to develop effective therapies. Investigators in the Lupus Center of Excellence, in collaborationwith the McGowan Institute for Regenerative Medicine, the Center for Vascular Remodeling and Regeneration, and the Department ofBioengineering have recently reported successful development of the first experimental model for ex vivo investigation of vascular stiffness andatherosclerosis in a mouse model. This multidisciplinary team, using a laser-based perfusion system, successfully measured the progressionof vascular stiffness, an early sign of atherosclerosis, in the aortas of mice deficient in apolipoprotein E. Additional studies, performed incollaboration with the Center for Biologic Imaging, simultaneously identified pathologic inflammatory and immune responses within the vesselwall during progression of the disease. These advances can now be extended to investigate atherosclerosis in mouse models of lupus and otherhuman vascular disorders and to identify potential targets for therapeutic intervention in humans.SELECTED SCHOLARLY ACTIVITIESStudy sections (excluding ad hoc review), editorial boards, and other honorsGrant ReviewJoseph M. Ahearn NIH NIAMS Special Emphasis Panel, Chair: ZAR MLB-L 01 (K awards), 2006, Dept. of Veterans Affairs - Merit Review Board forImmunology, Wellcome Trust Scientific Reviewer, Lupus Panel; Department of Defense; Scientific Peer Advisory and Review NHLBI Study Section,Member, 200758 Better medicine through research and education.