Michael R. Elliott, PhD
Biography
Michael R. Elliott, PhD joined the Department of Microbiology and Immunology at the Whiddon College of Medicine as an associate professor. He received his Baccalaureate degree from Wake Forest University and his Ph.D. from the Wake Forest University School of Medicine. Dr. Elliott's research focuses on innate immunity, macrophage biology, and cancer immunotherapy. His laboratory is in the 猫咪社区APP Health Mitchell Cancer Institute (MCI).
Lab Mission
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. The goal of our work is to understand, at a mechanistic level, the function of tissue-resident macrophages and other myeloid populations as effectors of innate immunity in cancer immunotherapy, acute and chronic inflammation, aging, and microbial infection.
Our work focuses on several fundamental macrophage effector mechanisms, including motility, phagocytosis, and cytokine/chemokine responses to PAMPs and DAMPs. We study these processes using mouse genetic models, primary mouse and human leukocyte cultures, and a range of basic and advanced genetic, biochemical, and imaging techniques. Through our ongoing collaborations with multiple basic and clinical research labs, we ultimately seek to translate our research efforts into new disease therapies that harness the powerful immune-regulating properties of macrophages.
Macrophage Phagocytosis in Cancer
Macrophages are a key cell type in the regulation of cellular transformation, tumorigenesis, and anti-tumor immunotherapies. As such, there is increasing interest in translating our understanding of macrophages into effective anti-cancer therapies. In collaboration with clinical labs we have established two distinct projects that leverage our expertise in myeloid and macrophage biology to investigate novel roles for macrophages in hematologic malignancies:
1) Understand the mechanisms that regulate the rate and capacity of macrophages to engulf and kill malignant cells targeted by therapeutic monoclonal antibodies (mAbs). mAbs can be highly effective at reducing tumor burden, and one of the main mechanisms by which mAbs kill tumor cells is via antibody-dependent cellular phagocytosis (ADCP) mediated by tissue macrophages. While mAbs can be very effective, as monotherapies these mAbs are not curative, but the reasons for this are poorly understood. Recently, we discovered that macrophages have a finite capacity to engulf mAb-opsonized tumor cells and that this limitation could be a novel factor in therapeutic resistance to mAb therapies for many types of cancers. Our efforts to understand the mechanisms that regulate macrophage phagocytic capacity will lead to improved therapeutic application of mAbs in many diseases.
2) In a second project, we are carrying out detailed phenotyping and functional analyses of macrophage populations in the bone marrow and using this information to understand the specific roles of these macrophages in controlling inflammation that contributes to age-related marrow failure diseases and hematologic malignancies in preclinical mouse models.
Role of Macrophages in the Resolution of Tissue Inflammation
Macrophages are central regulators of inflammation and tissue repair. We recently discovered a novel role for the anti-inflammatory ecto-enzyme CD73 on macrophages in regulating the resolution and repair of tissues following inflammation. CD73 is the rate-limiting enzyme involved in the generation of extracellular adenosine 鈥� a powerful anti-inflammatory mediator that suppresses the function of numerous innate and adaptive immune cell populations.
The current focus of our work on CD73 is centered on understanding the role of CD73 in regulating macrophage-mediated inflammation in the contexts of aging (or 鈥渋nflammaging鈥�) in the lung, marrow, and peritoneum and in hematopoietic cell dysfunction. There is growing interest in CD73 as a therapeutic target for the treatment of numerous types of cancer. As such, our work will provide novel insights into the specific role of CD73 on macrophages in regulating tissue inflammation homeostatically and in disease settings, including cancer.