My major research interest has focused on "Proteomic Dissection of SLE Pathogenesis." Systemic Lupus Eryhematosus (SLE) is a systemic autoimmune disease with substantial morbidity and mortality. Important progress has been achieved in the genetic study of this disease during the last few decades. However, the mechanism of the development of lupus remains largely unknown due to the complex nature of this disease. More detailed information regarding the contribution of different proteins to this disease needs to be uncovered in order to understand the mechanism of this disease. Criticial biochemical details relating to each disease stage is still lacking. Hence, proteomics, as a counterpart of genomics, is being rapidly evolved into a powerful platform for the identificaiton of important proteins which might be responsible for each disease stage. In particular, there is an increasing role and demand for proteomics in the dissection of SLE pathogenesis, in the following 2 areas: 1) To dissect the signaling pathways which may potentially trigger the development of lupus or lupus nephritis, in order to uncover critical nodes in disease; 2) To discover potential early biomarkers for lupus or lupus nephritis. During the last few years, we have employed multiple proteomic approaches, including 2D-gel, Immunoproteome Array, Glomerular Antigen Array, Reverse Phase Protein Array, and iTRAQ to detail the lupus related proteomes both in mice and in patients. These studies include urine/serum proteomic analysis, and the elucidation of B-cell/T-cell/DC mediated signaling pathways in autoimmunity. So far, we have uncovered and validated a couple of novel biomolecules that appear to be hyper-excreted in lupus nephritis, some of which could potentially pan out as biomarkers for early diagnosis. Also, we examine around 200 signaling molecules in order to determine which particular signaling axes become particularly activated in leukocytes as disease evolves in lupus. We have found PI3K/AKT/mTOR, MAPK,NF-eB and Bcl-2 related pathways to be activated in the diseased lupus mice compared to the normal control, and we have observed that the inhibition of some of these axes can effectively ameliorate disease in murine lupus. Collectively, these studies will further our understanding of lupus and might become potentially important for the early diagnosis and treatment of this disease.
RESEARCH INTERESTS
Signaling transduction pathways of lupus and lupus nephritis.
Discovery of early biomarkers for lupus and lupus nephritis.
Target and inhibitors of lupus and lupus nephritis
RECENT PUBLICATIONS
Wu T, Xie C, Wang HW, Zhou XJ, Schwartz N, Calixto S, Mackay M, Aranow C, Putterman C, Mohan C., "Elevated Urinary VCAM-1, P-Selectin, Soluble TNF Receptor-1, and CXC Chemokine Ligand 16 in Multiple Murine Lupus Strains and Human Lupus Nephritis." J Immunol., 179(10):7166-75., November 2007
Wu T, Qin X, Kurepa Z, Kumar KR, Liu K, Kanta H, Zhou XJ, Satterthwaite AB, Davis LS, Mohan C., "Shared signaling networks active in B cells isolated from genetically distinct mouse models of lupus." J Clin Invest., 117(8):2186-96., July 2007
Wu T, Xie C, Bhaskarabhatla M, Yan M, Leone A, Chen SS, Zhou XJ, Putterman C, Mohan C., "Excreted Urinary Mediators in Immune Nephritis with Potential Pathogenic Significance" Arthritis & Rheumatism, 56(3):949-959, 2007
Wu T, Mohan C., "Proteomics on the Diagnostic Horizon-Lessons from Rheumatology" Am. J. Med. Sci., 333(1):16-25, 2007
Wu T. Mohan C., "Three Pathogenic Determinants in Immune Nephritis -- Anti-glomerular Antibody Specificity, Innate Triggers and Host Genetics" Frontiers in Biosciences, 12:2207-2211, 2007
SIGNIFICANT PUBLICATIONS
Wu T, Qin X, Kurepa Z, Kumar KR, Liu K, Kanta H, Zhou XJ, Satterthwaite AB, Davis LS, Mohan C., "Shared signaling networks active in B cells isolated from genetically distinct mouse models of lupus." J Clin Invest. 2007 Jul 19; [Epub ahead of print], 117 July 2007
Tianfu Wu, Chun Xie, Madhavi Bhaskharabtla, Amanda Leon, Xin J. Zhou, Chaim Putterman, and Chandra Mohan, "Excreted Urinary Mediators in Immune Nephritis with Potential Pathogenic Significance" Arthritis & Rheumatism, 56(3):949-959, 2007
Tianfu Wu and Chandra Mohan, "Proteomics on the Diagnostic Horizon-Lessons from Rheumatology" Am. J. Med. Sci., 333(1):16-25, 2007
Quan Li, Chun Xie, Tianfu Wu, Meggan Mackay, Cindy Aranow, Chaim Putterman, Chandra Mohan, "Glomerular Proteome Arrays -- A Novel Approach to Uncover Autoantibody Clusters that best Predict Disease Activity in Lupus" The Journal of Clinical Investigation, 115(12):3428-3439, 2005
Ioannis Vakonakis, Jingchuan Sun, Tianfu Wu, Andreas Holzenbug, Susan S. Golden, Andy C. Liwang, "NMR Structure of the KaiC-Interacting C-terminal Domain of KaiA, a Circadian Clock Protein: Implication for KaiA-KaiC Interaction" Proc. Natl. Acad. Sci. USA, 101:1479-1484, 2004
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