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Research at Mass General
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Principal Investigator, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital
Associate Physician, Rheumatology Unit, Department of Medicine, Massachusetts General Hospital
Associate Professor of Medicine, Harvard Medical School
The Bloch Laboratory investigates the role of the bone morphogenetic protein signal transduction pathway in a broad spectrum of human diseases, including iron overload syndromes, anemia, inflammation, Sjogren’s syndrome, non-alcohol related fatty liver disease, calciphylaxis and atherosclerosis. In addition, members of the laboratory investigate the structure and function of human autoantigens, with the intention of determining the role of these antigens in the pathogenesis of autoimmune diseases. The laboratory also studies the functional significance of genetic polymorphisms associated with hypertension.
The current research program focuses on three areas:
The role of the bone morphogenetic protein signaling pathway on the pathogenesis of human diseases, including inflammation, anemia, vascular calcification and atherosclerosis.
Ongoing studies use mice lacking components of the BMP signaling pathway to investigate the role of the BMP signaling in iron homeostasis and the innate immune system. In addition, we are examining the effects of blocking BMP receptors, using small molecule inhibitors, on the anemia of inflammation and the development of atherosclerosis.
Identification and characterization of novel, primary biliary cirrhosis-related, human autoantigens.
We have used the antibodies in the serum from more than 700 patients with this organ specific autoimmune disease to study the structure and function of two novel cellular structures: the PML-Sp100 nuclear body and the cytoplasmic mRNA processing body. Mutations in the gene encoding one autoantigen within the PML-Sp100 nuclear body, designated Sp110, were found to cause an immunodeficiency disorder known as “VODI” (veno-occlusive disease with immunodeficiency). Ongoing studies are examining the role of Sp110 in the maturation of cells involved in host defense, including B and T lymphocytes and monocytes.
The functional analysis of genetic polymorphisms associated with hypertension.
In collaboration with Dr. Newton-Cheh in the Division of Cardiology and Emmanuel Buys in the Anesthesia Center for Critical Care Research , we are characterizing the functional significance of genetic polymorphisms associated with increased blood pressure. A rare polymorphism in the gene encoding atrial natriuretic peptide (ANP) was found to be associated with decreased blood pressure. We showed that the polymorphism was within the seed sequence of microRNA 425, making the mRNA encoding ANP relatively resistant to degradation and increasing the level of circulating ANP. Ongoing studies are examining the functional significance of polymorphisms within other component of the ANP signaling pathway.
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