Immune Disease Institute

The Shimaoka lab is interested in the underlying mechanism by which the activity of cell adhesion molecule integrins on leukocytes is regulated in health and diseases.

The affinity of leukocyte integrins for their ligands is dynamically regulated through an incompletely characterized process that is essential for maintaining an appropriate level of adhesion during immune surveillance and activation. Deregulation of integrin activation is thought to either perturb host defense (as seen in a genetic disorder, leukocyte adhesion deficiency) or induce tissue destruction through autoimmunity (as in psoriasis and inflammatory bowel diseases). Shimoaka and collegues study the posttranscriptional mechanisms (e.g. miRNA) that control integrin activation as well as the structural basis of how small-molecule chemicals such as volatile anesthetics modify integrin activation.

A prototypic leukocyte integrin-targeted therapy is designed to interfere with the adhesive interactions of immune cells, primarily focusing on anti-inflammation only. We explore the utility of leukocyte integrin-targeting across a broad range of hematologic cell-related diseases (e.g., blood cancer: myeloma/leukemia; inflammation: colitis/psoriasis; and viral infection). Shimoaka and colleagues have developed a novel strategy to comprehensively manipulate leukocyte functionalities, the integrin-targeted stabilized nanoparticles (I-tsNP) for delivering siRNAs to hematologic cells in vivo.

Motomu Shimaoka received his M.D. (1989) and Ph.D. (1997) from Osaka University in Suita, Japan. After serving as a staff physician at an intensive care unit in Osaka University Hospital, he joined Tim Springer's laboratory at IDI, where he studied the structures of integrin LFA-1 and Mac-1. He received an ASH-Stratton-Jaffé Fund Scholar Award from the American Society of Hematology in 2004 and NIH grants including the Challenge Grant in 2009.