Research

Research Focus

We cloned and characterized two important human erythrocyte membrane skeletal proteins, namely protein 4.2 and E-tropomodulin. We discovered that protein 4.2 is a transglutaminase-like molecule without the cross-linking capability and proposed a hypothesis for protein 4.2 and transglutaminase to regulate the mechanical properties of erythrocyte membranes. We also identified two specific isoforms of tropomyosin (TM) in erythrocyte membranes and revealed that E-tropomodulin binds to the N-terminus of tropomyosin.

We further mapped the binding sites involved in the TM/E-tropomodulin interaction. The complex formed by TM5/5b and E-tropomodulin may function as a molecular ruler in determining the length of the actin protofilaments and thus the geometry of erythrocyte membrane skeleton.

More recently we created a E-tropomodulin-null mutation in mouse embryonic stem cells and mice. This allows us to investigate the role of E-tropomodulin in the mechanical properties of both erythroid and non-erythoid cells (e.g., cardiomyocytes and skeletal muscles) that express E-tropomodulin at a significant level. The knockout mice die embryonically with arrests in cardiac morphogenesis, yolk sac vasculogenesis, and embryo proper hematopoiesis.

Figures

3-D Nanomechanics of an Erythrocyte Junctional Complex in Equibiaxial and Anisotropic Deformations The influence of fluid shear stress on the remodeling of the embryonic primary capillary plexus E-Tmod capping of actin filaments at the slow-growing end is required to establish mouse embryonic circulation Protofilament and hexagon: A three-dimensional mechanical model for the junctional complex in the erythrocyte membrane skeleton Genomic organization of mouse and human erythrocyte tropomodulin genes encoding the pointed end capping protein for the actin filaments Tropomodulin-Binding Site Mapped to Residues 7±14 at the N-Terminal Heptad Repeats of Tropomyosin Isoform 5 Tropomyosin isoform 5b is expressed in human erythrocytes: implications of tropomodulin-TM5 or tropomodulin-TM5b complexes in the protofilament and hexagonal organization of membrane skeletons E-Tmod capping of actin filaments at the slow-growing end is required to establish mouse embryonic circulationE-Tmod capping of actin filaments at the slow-growing end is required to establish mouse embryonic circulation

Other Interests

  • Creation of mouse models with targeted disruption of specific genes.
  • Theory on the molecular ruler and geometry of erythrocyte membrane skeletons.
  • Mapping protein binding sites with recombinant proteins.
  • cDNA and genomic characterization of genes important for cell and membrane mechanics.
  • Mechanical properties of genetically engineered cells and tissues.
  • Molecular and mechanical defects in diseases (e.g., of heart, vessels, blood, and muscle).