Primary AppointmentMicrobiology, Immunology, and Cancer Biology
Contact InformationTelephone: 434.982.3227
Macrophage effector functions in inflammation and immunotherapy
The focus of our research is to understand, at a mechanistic level, the function of tissue-resident macrophages as effectors of innate immunity in acute and chronic inflammation, infection, and cancer. Macrophages are a phenotypically diverse, multifunctional population of immune cells found in every tissue in the body that play key roles in maintaining normal tissue function and immune defense against pathogens. Our work focuses on defining the molecular pathways that regulate macrophage motility, phagocytosis and inflammatory responses related to their roles in the clearance of dying cells and cancer cells. We use a wide range of basic and advanced genetic, biochemical, and imaging techniques to address these questions. Through ongoing collaborations with multiple basic and clinical labs, we ultimately seek to translate our research efforts into new disease therapies that harness the powerful immune-regulating properties of macrophages. Project Area 1: Macrophage Phagocytosis in Cancer. Macrophages are now established as a key cell type in the regulation of cellular transformation, tumorigenesis, and anti-tumor immune therapies. As such, there is increasing interest in translating our understanding of macrophages into effective anti-cancer therapies. Through collaborations with multiple clinicians, my lab has established two distinct projects that leverage our expertise in myeloid and macrophage biology to investigate novel roles for macrophages in hematologic malignancies: 1)Mechanisms of mAb-mediated malignant cell clearance by macrophage phagocytosis, and 2) Role of bone marrow macrophages in hematologic malignancies. Project Area 2: Role of Macrophages in the Resolution of Tissue Inflammation. Macrophages are central regulators of inflammation and tissue repair. We have discovered a novel role for the anti-inflammatory ecto-enzyme CD73 on macrophages in regulating the resolution and repair of tissues following inflammation. We have two projects related to the role of CD73 in resolving tissue inflammation: 1) Immunoregulatory role of CD73 in acute inflammation, and 2) Contribution of CD73 on inflammaging and hematopoietic dysfunction. Project Area 3: Bone Marrow Macrophage Regulation of Erythropoiesis. Anemia is a massive worldwide source of disability, afflicting one third of the world?s population. Erythroid-associated macrophages (EA-Macs) provide a fundamental phagocytic function in hematopoietic organs by the clearance of extruded nuclei from reticulocytes in the terminal stages of erythropoiesis. In collaboration with the Palis Lab (U. Rochester), our overall goal is to define the specific functions of marrow-resident macrophages in the regulation red blood cell production.