Immunology
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Vicki Rubin Kelley

Department of Medicine
Brigham and Women's Hospital
Harvard Institutes of Medicine
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-525-5915
Fax: 617-525-5830
email:vkelley@rics.bwh.harvard.edu

  

My laboratory focuses on the molecular mechanisms of autoimmune disease. More specifically, we are investigating the attack mechanisms instrumental in targeted tissues for autoimmune destruction. Conversely, we probe for the barriers which protect these tissues from autodestruction. Our penultimate goal is to identify the cells and molecules instrumental in inciting and promoting autoimmune tissue damage. The final goal is to construct a therapeutic strategy to block autoimmune tissue destruction. The majority of our studies have concentrated on autoimmune disease and renal inflammation. Our initial clues to unravel the molecules pivotal in inciting tissue injury are determined by identification of the pathologic cells in the tissues and understanding the molecules which foster their survival and proliferation. Once we identify the molecule required for the pathologic cell, we determine whether it is expressed in the tissue prior to tissue injury. We then hunt for the cells secreting this candidate molecule. To establish whether this candidate molecule fosters or thwarts tissue injury we introduce the molecule into the tissue using genetic approaches. We use transgenic, gene knock-out and gene transfer strategies to test the importance of a selected molecule in the autodestructive process. Once we establish that the selected molecule is instrumental in the pathogenesis, we investigate which cells produce this molecule and determine the receptor regulation. For example, using these cellular and genetic approaches have established that macrophage growth factors and b-chemokines can target autoreactive T cells to the kidney and incite autoimmune destruction. We have identified that dual delivery of macrophage growth factors and specific cytokines can amplify the tissue destructive process.

The current projects focus on detailing the role of : 1) individual isoforms of the macrophage growth factor (CSF-1) in autoimmune lupus and renal inflammation using genetically modified mice, 2)co-stimulatory pathways as regulators of lupus, 3) macrophage biology linked to lupus and 4)chemokines as therapeutic targets for lupus. Our future goals include novel strategies identify and deliver therapeutics to halt autoimmune tissue damage and provide an enduring barrier to preserve tissue function.

 

Papers & Publications:

  1. Kinoshita K, Tesch, G, Schwarting A, Maron R, Sharpe AH, Kelley VR. Costimulation by B7-1 and B7-2 Is Required for Autoimmune Disease in MRL-Faslpr Mice. J Immunol 2000; 164:6046-6056.
  2. Shinozaki M, Hirahashi J, Lebedeva T, Liew FY, Salant DJ, Maron R, Kelley VR. IL-15, a survival factor for kidney epithelial cells , counteracts apoptosis and inflammation during nephritis. J. Clin Invest 2002; 109: 951-960
  3. Lenda DM, Kikawada E, Stanley ER, Kelley VR. CSF-1 dependent macrophage proliferation, and activation results in tubular apoptosis during renal inflammation. J Immunol 2003;170:3254-3262.
  4. Kikawada E, Lenda DM, Kelley VR. IL-12 deficiency in MRL-Faslpr mice: Delays nephritis and intrarenal IFN-g production, and reduces systemic pathology. J Immunol 2003; 170:3915-3925.
  5. Lenda DM, Stanley ER, Kelley VR. Negative Role of Colony Stimulating Factor-1 in Macrophage, T, and B Cell Mediated Autoimmune Disease in MRL-Faslpr Mice. J. Immunol 2004; 173:4744-4754.