Jason M. Wooden, PhD
I am using newly developed quantitative proteomic methodology to better understand the pathophysiology of a class of red blood cell (RBC) genetic disorders know as hereditary hemolytic anemia.  A normal healthy RBC has a biconcave shape that gives it the strength and flexibility to survive shear stress during circulation and traverse the narrowest of capillaries.  This unique shape arises from a structure known as the RBC membrane skeleton that supports the plasma membrane.  It consists of a network of proteins organized around a hexagonal array of spectrin tetramers crosslinked by actin filaments:

Defects in the RBC membrane skeleton can cause hereditary hemolytic anemia.  The result is an abnormally shaped RBC which is fragile and prematurely lost from circulation.  Mutations in adducin, ankyrin, band 3, protein 4.2, and spectrin have all been reported to result in abnormal RBCs.  I am studying the protein profiles of normal and hereditary hemolytic anemia RBCs to address several outstanding issues.  First, not all clinical cases are accounted for by the currently known membrane skeleton defects.  Secondly, fundamental questions remain unanswered surrounding the clinical variability and non-erythroid effects of known RBC membrane skeleton mutations. 

Past RBC analysis has been hampered by the complexity of the system and limitations in detecting low abundance proteins.  High throughput tandem mass spectrometry offers a less biased approach to globally profile RBC protein interactions.  These analyses will help define a core set of proteins for the normal RBC that can be compared with the profile for diseased RBCs.  Our hypothesis is that alterations in the structure and or abundance of specific proteins will represent candidates that may be involved in disease severity and pathophysiology in non-erythroid cells.  The hope is that a deeper understanding of protein-protein interactions within the RBC can provide new insights into inherited hemolytic anemia.