My research focuses on how metalloproteases degrade peptides in the CNS.  I use structural and molecular biology in conjunction with enzymology to understand the mechanisms of degradation for a family of metalloproteases termed cryptidases.  This family includes insulin-degrading enzyme (IDE), presequence peptidase (PreP), neprilysin and the endothelin-converting enzymes (ECE).  Cryptidases are unique because they can degrade unique or shared substrates.  For instance, IDE is classically associated with degrading insulin with high affinity.  Yet it is also capable of degrading amyloid-beta, the peptide implicated in the pathophysiology of Alzheimer's disease.  Cryptidases are also unique in that they possess an internal chamber, a unique feature of globular proteins and so suggests a potential mechanistic role. Improved understanding of the structure of these enzymes and how they function in the nervous system will facilitate better understanding of their mechanisms and provide putative therapeutic strategies.

 http://tang.bsd.uchicago.edu

Selected Publications

Hulse RE, Winterfield J, Kunkler PE, Kraig RP (2001) “Astrocytic Clasmatodendrosis in hippocampal organ culture”, Glia Feb:33(2):169-179.

Hulse RE, Kunkler PE, Kraig RP (2004) “Optimization of multiplexed bead-based cytokine immunoassays for rat serum & brain tissue”, J Neuroscience Method, Jun:136(1):87-98.

Kunkler PE, Hulse RE, Kraig RP (2004) “Multiplexed Cytokine Protein Expression Profiles from Spreading Depression in Hippocampal Organotypic Cultures”, J Cerebral Blood Flow and Metabolism, Aug:24(8):829-839.

Kunkler PE, Hulse RE, Schmitt M, Nicholson C, Kraig RP (2005) “Optical current source density analysis in hippocampal organ culture shows spreading depression occurs with uniquely reversing currents” J Neuroscience Apr 13(15):3952-3961.