Joshua Astern

  Pathology and Laboratory Medicine

346 MacNider Bldg, CB# 7155

Lab Phone: 966-2561x232

Lab Fax: 966-4251
3rd Year IVB Trainee
4th Year Graduate Student
 
Ph.D. Project Description:
Myeloperoxidase in Vascular Disease and Autoimmunity: Given the prominent role of neutrophils and monocytes in acute and chronic inflammation, respectively, it is critical to understand the functional link between granule proteins and vascular injury. Myeloperoxidase is an abundant granule constituent that when released into circulation is internalized by endothelial cells and interferes with normal vascular function. One of my projects regards the "hunt" for an endothelial MPO receptor; identification of this receptor may provide novel therapeutic targets for inflammatory disease as well as reveal new, non-bactericidal roles not yet associated with this protein. This first project explores the functional effects of the MPO-endothelial cell interaction. My second project explores MPO and its properties that contribute to its autoantigenicity. Being that individuals are constantly exposed to myeloid granule proteins throughout life, it is perplexing that some patients generate an autoimmune response specifically targeting MPO. We hypothesize that our published Theory of Autoantigen Complementarity will explain the pathogenesis of MPO-antineutrophil cytoplasmic autoantibody (MPO-ANCA) disease. This theory states that autoimmunity is not incited by the autoantigen, but rather a protein complementary in surface structure to the autoantigen, i.e. a protein with identity to the amino acid sequence of the translated antisense RNA from the autoantigen gene. The complementary protein incites production of antibodies that elicit a secondary anti-antibody, or anti-idiotypic response. The anti-idiotypic antibody then recognizes and reacts with the autoantigen. Previously published data from our lab provides support for each component of this theory, but does not allow us to prove causation. We expect to demonstrate induction of autoimmune disease in a mouse model by immunization with recombinant complimentary MPO (cMPO) polypeptides. Additionally, we will determine if the components of our theory apply to human MPO-ANCA disease. Overall, this work will seek to unveil novel functions of MPO in the context of inflammation and explore the properties of this protein that contribute to its autoantigenicity.
Principle Investigator:
Dr Ronald Falk, MD and Gloria Preston, PhD
 
IVB Collaborator:
Dr J. Charles Jennette
Project Description:
   mouse models for MPO-ANCA and the theory of autoantigen complementarity
   
Rotations:
   William Coleman, PhD: Early immediate gene expression following partial-hepatectomy in livers of retrorsine-treated rats
  Susan Lord, PhD: Early events of fibrinogen polymerization studied by multi-angle dynamic light scattering
 
 
Familiar Techniques:
   western blotting, ELISA, recombinant protein production and purification, subcloning
Other Techniques used in Laboratory:
  
 
Undergraduate degree:
   B.S. in Microbiology and Cell Science (1999) from University of Florida, Gainesville, Florida
Other Professional/ Graduate degree(s):
  

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