My laboratory is interested in the biology of human natural killer (NK) cells and how they contribute to disease processes. NK cells are critical participants in innate immunity and have the ability to recognize and kill virally infected cells and tumor cells. Based on their ability to recognize immune molecules termed human leukocyte antigens (HLA), NK are able to discriminate between cells that are “self” from foreign or damaged cells. One family of receptors that recognize these HLA molecules are termed killer Ig-like receptors (KIR) and are found on the surface of NK cells. Interaction of the NK cell and its potential target cells through engagement of KIR and HLA molecules leads to one set of NK actions; importantly, non-engagement of KIR and HLA molecules leads to another set of NK actions. Genes encoding KIR and HLA can therefore be used to predict these actions and therefore NK behavior in certain disease states.
One focus of the laboratory is the role of NK cells in controlling leukemia relapse in bone marrow transplants. We have shown that specific combinations of KIR and HLA genes can be predictive of improved outcomes in transplant patients. Translating these findings back to the bedside, we are using this information to select donors for bone marrow transplants and are also exploring ways to select donors for NK infusion to treat patients whose disease has relapsed.
Transferring the information that we have learned from transplants for leukemia, we are investigating the role of NK cells in controlling other diseases treated with transplants, specifically the pediatric tumor neuroblastoma. These studies have led to a new treatment protocol combining the use of monoclonal antibodies with NK cells for the treatment of high-risk neuroblastoma patients.
Improved understanding how NK cells behave is critical to advancing our ability to harness their innate capacity for tumor recognition and eradication. Therefore, an important component of the laboratory focuses on the basic biology of the NK cell, identifying the molecules involved in controlling NK action, and determining the laboratory and clinical conditions under which NK actions can be modified.
Our research bridges both basic biology research and clinical research. Because of the translational nature of the research, laboratory members include both basic scientists and clinicians. Fundamental to our work is the generous contribution of the transplant and neuroblastoma services: the patients, physicians and the clinical staff, without whom this work could not be possible.