Center for Comparative Medicine
SOM: Medical Microbiology and Immunology
University of California, Davis
Research Interest: Innate immune responses to viral infection and malignancy, Development and function of natural killer cells in humans and animal models, Non-human primate model of viral infection.
We study innate immune cell responses to infectious disease and malignancy, with a particular focus on natural killer (NK) cells, the third major population of lymphocytes. Our current research is aimed at understanding how NK cells mount effective immune responses against viral infections (e.g., herpesviruses, retroviruses and influenza virus). We have recently discovered a novel subset of human NK cells that displays very potent anti-viral responsiveness. This subset is characterized by deficient expression of the signaling adaptor FcRy, which normally associates with the IgG Fc receptor (CD16) as a homo-dimer or a hetero-dimer with CD3ç, a second CD16-associated adaptor, as observed in conventional NK cells (cartoon below). However, FcRy-deficient NK cells, termed 'g-NK cells', express CD3ç at normal levels. Importantly, we have found that g-NK cells exhibit greatly enhanced functional and proliferative responses toward target cells infected with a variety of viruses in the presence of virus-specific antibodies (Ab).
We have detected g-NK cells in approximately 40% of the healthy donors tested, and the presence of these cells is associated with prior infection by cytomegalovirus (CMV), a common herpesvirus that infects billions of people worldwide.
Our research aims to understand 1) how g-NK cells function better than conventional NK cells, 2) how g-NK cells are generated and maintained, and 3) what role g-NK cells play in immune responses to viral infections.
We are also pursuing a better understanding of NK cell functional and proliferative responses during hematopoiesis following bone marrow transplantion in humans, and during viral infection in rhesus macaques. In particular, we are working to identify molecular and biochemical mechanisms by which NK cells are activated in response to infection with CMV or SIV. We are also investigating the role that g-NK cells play in anti-tumor responses.