In addition to research already being funded and previously reported, additional grant applications have been reviewed and approved by various members of AARDA's Scientific Advisory Board. Here are a few of the newer studies now in progress.

• "Epigenetics and copy number variations in monozygotic twins discordant for primary biliary cirrhosis" - Highly relevant to understanding the pathogenesis of primary biliary cirrhosis and potentially other autoimmune fibrosing conditions. Although the investigation of epigenetic factors as causative in autoimmune diseases is not novel, its application to identical twins discordant for disease adds a novel twist. - Carlo Selmi, M.D., Ph.D., University of California, Davis

• "Phase II BCG Human Clinical Trial to Reverse Type 1 Diabetes" - The specific aim of the generic drug bacillus Calmette-Guerin (BCG) Human Clinical Trial Program is to investigate whether vaccination with BCG will eliminate the pancreas-destroying autoreactive T lymphocytes in humans with advanced type 1 diabetes and bring forward a new, inexpensive, non-toxic treatment for type 1 diabetes. The Phase II study is the next step to determine the best dose of BCG and optimal timing of administration to potentially eliminate the autoreactive T cells in type 1 diabetes. - Denise Faustman, M.D., Ph.D., Massachusetts General Hospital, Boston, Massachusetts

• "Development of novel mouse model of congenital complete heart block" - Congenital complete heart block (CCHB) is autoantibody-induced injury to the heart of the fetus carried by a mother with systemic autoimmune disease (50 percent of babies affected with CCHB) will die). In the current proposal, the researchers are using new strategies and utilizing their profound experience with animal models in an effort to investigate the pathogenesis of CCHB. - Daniela Chihakova, M.D., Ph.D., Johns Hopkins University, Baltimore, Maryland

• "Immunological resetting by HSC transplantation for SLE treatment" - Hematopoietic stem cell transplantation (HSCT) aims to eradicate autoreactive immune cells by chemoablation and restore a normal immune system with newly transplanted hematopoietic stem cells (HSCs). This approach has been attempted to cure patients with severe lupus who are not responsive to conventional therapy. Disease-free remission has been achieved in some patients treated with HSCT although one third of patients relapsed shortly afterward. Results gained from this study could facilitate the development of a better HSCT treatment for lupus. - Haitao Niu, Ph.D., The Feinstein Institute for Medical Research, Manhasset, New York

• "Differential expression of microRNAs and sexual dimorphism in autoimmune diseases" - Although various genome- and sex hormone-based hypotheses have been proposed for the female prevalence of autoimmune diseases, there is so far no consensus ont he cause and mechanism of sexual differences in autoimmune diseases. Recently discovered microRNAs (miRNAs) have emerged as key regulators of homeostasis of the immune system. In this study, researchers will investigate whether the differential expression of miRNAs contributes to the female prevalence of autoimmune diseases, an aspect not studied so far. - Rujuan Dai, Ph.D., Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia

• "Role of Sex Hormones in Regulation of Interferon Genes in Autoimmunity (SLE)" - Lupus is a female-biased disease. The investigator has expressed the hypothesis that estrogen regulates interferon genes and that the regulation differs in males and females. The study results should provide the preliminary data needed to undertake a full-scale study of induction of interferon genes in males and females as well as in lupus patients and appropriate controls. - Ram P. Singh, Ph.D., University of California, Los Angeles

• "Gene Therapy of Primary Biliary Cirrhosis" - Primary biliary cirrhosis (PBC) is a model autoimmune disease of the liver characterized by well-defined tissue damage of the small bile ducts and the presence of autoiantibodies directed against specific mitochondrial proteins. It is recognized that immune response to one of the mitochondrial proteins, pyruvate dehydrogenase E2 (PDC-E2) is the culprit. The researchers believe that if they can prevent this specific immune response to PDC-E2, liver damage can be avoided. They will use a new gene therapy approach and mouse models of PBC to verify their hypothesis. This method, if successful, can also be applied to other autoimmune diseases. - Patrick S.C. Leung, Ph.D., University of California, Davis