Current Research and Scholarly Interests
We study the biology of immune cells and their roles in the pathogenesis of cancers and other life-threatening diseases. By applying new and more precise analytical tools for assessing this system in mice and humans, we have been successful at identifying disease-promoting immune abnormalities. By targeting the cells responsible for or affected by these abnormalities, we have succeeded in reversing the abnormalities and ameliorating the diseases they cause. These advances would not have been possible without a collaborative research environment in which individuals are encouraged to pursue their own high-risk/high-reward ideas.
We have been particularly interested in the biology and functions of dendritic cells (DC), which are potent antigen presenting cells that can either induce or suppress immunity. Our first generation methods for isolating and arming human DC with tumor antigens provided the basis for the Sipuleucel-T vaccine that was approved by the FDA in 2010 for the treatment of metastatic prostate cancer. More recently, my lab developed a novel immunotherapeutic strategy that targets tumoral DC in vivo. In addition, we have been using newer technologies, including high dimensional single cell proteomic technology (CyTOF) and deep gene sequencing to investigate the immune system in cancer. Our goal is to identify and understand the key cellular and molecular mechanisms required for tumor elimination. Although we study human tissues in all of our projects, we also make extensive use of mouse models for in depth mechanistic studies.
In addition to cancer, we have been studying the role of immune cells in autoimmune diseases, metabolic diseases, graft versus host disease and transplantation tolerance. Recently, our group has developed novel tools for studying microglia and macrophages in the brain and we have begun to use these tools to analyze the role of these rare immune cells in chronic neurodegenerative disorders such as Alzheimer?s Disease, Parkinson?s Disease and amyotrophic lateral sclerosis (ALS). Our preliminary findings in mouse models suggest that abnormal metabolism affecting these cells may contribute to the development of these disorders.