Welcome to the Huang Laboratory in the Departments of Pathology and Microbiology and Immunology at the Geisel School of Medicine at Dartmouth, located at the Dartmouth Hitchcock Medical Center in Lebanon, New Hampshire.
T lymphocytes are a critical component of the adaptive immune system and provide specific protection against pathogens and cancer cells. Defects in T cell activation or migration lead to primary immunodeficiency diseases, characterized by increased susceptibility to viral and bacterial infections. However, T cell hyperactivity can result in autoimmune attack of one’s own tissue. The quality and magnitude of a T cell response are controlled by positive and negative cues from the T cell microenvironment. We investigate how T cells appropriately and inappropriately translate activation and migration cues.
To identify critical genes that regulate T cell activity, we first performed a forward genetics screen to identify mutations that result in reduced T cell numbers. Using this approach, we identified Itk and Mst1 protein kinases as important regulators of T cell activation and migration, respectively. Mutations in Itk or Mst1 in both mice and human patients result in immunodeficiency disease. Our current focus is on elucidating how differences in the magnitude and kinetics of Itk and Mst1 activity determine the quality of the T cell response. Better understanding of Itk and Mst1 regulation is expected to provide new therapeutic strategies for the treatment of T cell-dependent diseases.