As a physician-scientist, my laboratory focuses on basic, translational, and clinical studies in the field of innate immunity, primarily focused on natural killer (NK) cells. Basic research questions focus on the molecular mechanisms that control NK cell development and function, utilizing both model organisms and primary human NK cells. As a fundamental post-transcriptional regulatory mechanism in hematopoietic cells, we have elucidated the expression and functional impact of microRNAs in controlling NK cell biology. Additional studies have established the critical importance of the lipid phosphatase PTEN in regulating the PI3K pathway and thereby impacting NK cell trafficking and functionality in vivo. Translational research questions focus on how cytokine receptor based signaling augments NK cell proliferation, survival, and anti-tumor functionality. These studies have revealed innate memory-like responses in human NK cells following combined cytokine pre-activation, which results in long-lived enhanced functional capacity against cancer cells. These findings have been translated into a first-in-human immunotherapy clinical trial of adoptive memory-like NK cells in leukemia patients, which includes an in depth study of human memory-like NK cell biology in vivo. Additional studies focus on how signals through the IL-15 receptor sustain and prime NK cell responses to cancers. In a more recent direction, my laboratory also investigates the pathogenic and clinical impact of somatic genomic alterations in malignant lymphocytes, specifically lymphoma.
Todd A. Fehniger, MD, PhD