Michael R. Elliott

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Primary Appointment

Associate Professor, Microbiology, Immunology, and Cancer Biology

Education

  • BS, Biology, Wake Forest University
  • PhD, Microbiology and Immunology, Wake Forest University School of Medicine

Research Disciplines

Cancer Biology, Cell and Developmental Biology, Immunology, Molecular Biology, Neuroimmunology

Research Interests

Macrophage effector functions in inflammation and immunotherapy

Research Description

The research focus in the Elliott Lab is to understand the function of tissue-resident macrophages as effectors of innate immunity in acute and chronic inflammation, 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 advanced genetic, biochemical, transcriptomics, and imaging techniques to address these questions. Through 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.
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) 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 (Pinney et al. 2020. Blood). 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 (Frisch et al. 2019. JCI Insights).
Project Area 2: 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 (Murphy et al. 2017. Cell Death Diff.). CD73 is the rate-limiting enzyme involved in the generation of extracellular adenosine â 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 âinflammagingâ) 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.
Project Area 3: Bone Marrow Macrophage Regulation of Erythropoiesis.
Anemia is a massive worldwide source of disability, afflicting one third of the worldâs population. Erythroid-associated macrophages (EA-Macs) provide a fundamental phagocytic function in hematopoietic organs through the clearance of extruded nuclei (called âpyrenocytesâ) 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 of red blood cell production. Currently, we are investigating the molecular mechanisms that enable EA-Macs to selectively engulf pyrenocytes at a tremendously high rate while maintaining appropriate support for developing erythroid cells. To address these questions, we are using automated high-dimensional flow cytometry analysis in combination with single cell transcriptomics in mouse models of erythropoiesis and anemia.

Training

  • Cancer Research Training in Molecular Biology
  • Interdisciplinary Training Program in Immunology

Selected Publications

2022

Pinney, J. J., Blick-Nitko, S. K., Baran, A. M., Peterson, D. R., Whitehead, H. E., Izumi, R., . . . Chu, C. C. (2022). The highly selective Bruton tyrosine kinase inhibitor acalabrutinib leaves macrophage phagocytosis intact. HAEMATOLOGICA, 107(6), 1460-1465. doi:10.3324/haematol.2021.279560

Owlett, L. D., Karaahmet, B., Le, L., Belcher, E. K., Dionisio-Santos, D., Olschowka, J. A., . . . O'Banion, M. K. (2022). Gas6 induces inflammation and reduces plaque burden but worsens behavior in a sex-dependent manner in the APP/PS1 model of Alzheimer's disease. JOURNAL OF NEUROINFLAMMATION, 19(1). doi:10.1186/s12974-022-02397-y

2021

Medina, C. B., Chiu, Y. -H., Stremska, M. E., Lucas, C. D., Poon, I., Tung, K. S., . . . Ravichandran, K. S. (2021). Pannexin 1 channels facilitate communication between T cells to restrict the severity of airway inflammation. IMMUNITY, 54(8), 1715-+. doi:10.1016/j.immuni.2021.06.014

2020

Zent, C. S., Pinney, J. J., Chu, C. C., & Elliott, M. R. (2020). Complement Activation in the Treatment of B-Cell Malignancies. ANTIBODIES, 9(4). doi:10.3390/antib9040068

Chu, C. C., Pinney, J. J., Whitehead, H. E., Rivera-Escalera, F., VanDerMeid, K. R., Zent, C. S., & Elliott, M. R. (2020). High-resolution quantification of discrete phagocytic events by live cell time-lapse high-content microscopy imaging. JOURNAL OF CELL SCIENCE, 133(5). doi:10.1242/jcs.237883

2019

Arandjelovic, S., Perry, J. S. A., Lucas, C. D., Penberthy, K. K., Kim, T. -H., Zhou, M., . . . Ravichandran, K. S. (2019). A noncanonical role for the engulfment gene ELMO1 in neutrophils that promotes inflammatory arthritis. NATURE IMMUNOLOGY, 20(2), 141-+. doi:10.1038/s41590-018-0293-x

Hilt, Z. T., Pariser, D. N., Ture, S. K., Mohan, A., Quijada, P., Asante, A. A., . . . Morrell, C. N. (2019). Platelet-derived β2M regulates monocyte inflammatory responses. JCI INSIGHT, 4(5). doi:10.1172/jci.insight.122943

Frisch, B. J., Hoffman, C. M., Latchney, S. E., LaMere, M. W., Myers, J., Ashton, J., . . . Calvi, L. M. (2019). Aged marrow macrophages expand platelet-biased hematopoietic stem cells via interleukin-1B. JCI INSIGHT, 4(10). doi:10.1172/jci.insight.124213

2018

Safronova, A., Araujo, A., Camanzo, E. T., Moon, T. J., Elliott, M. R., Beiting, D. P., & Yarovinsky, F. (2019). Alarmin S100A11 initiates a chemokine response to the human pathogen Toxoplasma gondii. NATURE IMMUNOLOGY, 20(1), 64-+. doi:10.1038/s41590-018-0250-8

VanDerMeid, K. R., Elliott, M. R., Baran, A. M., Barr, P. M., Chu, C. C., & Zent, C. S. (2018). Cellular Cytotoxicity of Next-Generation CD20 Monoclonal Antibodies. CANCER IMMUNOLOGY RESEARCH, 6(10), 1150-1160. doi:10.1158/2326-6066.CIR-18-0319

Bhagwat, S. P., Gigliotti, F., Wang, J., Wang, Z., Notter, R. H., Murphy, P. S., . . . Wright, T. W. (2018). Intrinsic Programming of Alveolar Macrophages for Protective Antifungal Innate Immunity Against Pneumocystis Infection. FRONTIERS IN IMMUNOLOGY, 9. doi:10.3389/fimmu.2018.02131

2017

Elliott, M. R., Koster, K. M., & Murphy, P. S. (2017). Efferocytosis Signaling in the Regulation of Macrophage Inflammatory Responses. JOURNAL OF IMMUNOLOGY, 198(4), 1387-1394. doi:10.4049/jimmunol.1601520

Murphy, P. S., Wang, J., Bhagwat, S. P., Munger, J. C., Janssen, W. J., Wright, T. W., & Elliott, M. R. (2017). CD73 regulates anti-inflammatory signaling between apoptotic cells and endotoxin-conditioned tissue macrophages. CELL DEATH AND DIFFERENTIATION, 24(3), 559-570. doi:10.1038/cdd.2016.159

2016

Zent, C. S., & Elliott, M. R. (2017). Maxed out macs: physiologic cell clearance as a function of macrophage phagocytic capacity. FEBS JOURNAL, 284(7), 1021-1039. doi:10.1111/febs.13961

Elliott, M. R., & Ravichandran, K. S. (2016). The Dynamics of Apoptotic Cell Clearance. DEVELOPMENTAL CELL, 38(2), 147-160. doi:10.1016/j.devcel.2016.06.029

2015

Das, S., Sarkar, A., Choudhury, S. S., Owen, K. A., Derr-Castillo, V. L., Fox, S., . . . Ernst, P. B. (2015). Engulfment and Cell Motility Protein 1 (ELMO1) Has an Essential Role in the Internalization of Salmonella Typhimurium Into Enteric Macrophages That Impact Disease Outcome. CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY, 1(3), 311-324. doi:10.1016/j.jcmgh.2015.02.003

2014

Stevenson, C., de la Rosa, G., Anderson, C. S., Murphy, P. S., Capece, T., Kim, M., & Elliott, M. R. (2014). Essential Role of Elmo1 in Dock2-Dependent Lymphocyte Migration. JOURNAL OF IMMUNOLOGY, 192(12), 6062-6070. doi:10.4049/jimmunol.1303348

2011

Park, D., Han, C. Z., Elliott, M. R., Kinchen, J. M., Trampont, P. C., Das, S., . . . Ravichandran, K. S. (2011). Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein. NATURE, 477(7363), 220-U126. doi:10.1038/nature10340

Lu, Z., Elliott, M. R., Chen, Y., Walsh, J. T., Klibanov, A. L., Ravichandran, K. S., & Kipnis, J. (2011). Phagocytic activity of neuronal progenitors regulates adult neurogenesis. NATURE CELL BIOLOGY, 13(9), 1076-1U99. doi:10.1038/ncb2299

Sandilos, J. K., Chekeni, F. B., Elliott, M. R., Walk, S. F., Kinchen, J. M., Lazarowski, E. R., . . . Bayliss, D. A. (2011). Caspases Mediate Pannexin 1 Channel Activation in Apoptotic Cells. Biophysical Journal, 100(3), 101a. doi:10.1016/j.bpj.2010.12.759

Rao, J., Elliott, M. R., Leitinger, N., Jensen, R. V., Goldberg, J. B., & Amin, A. R. (2011). RahU: An inducible and functionally pleiotropic protein in Pseudomonas aeruginosa modulates innate immunity and inflammation in host cells. CELLULAR IMMUNOLOGY, 270(2), 103-113. doi:10.1016/j.cellimm.2011.05.012

2010

Chekeni, F. B., Elliott, M. R., Sandilos, J. K., Walk, S. F., Kinchen, J. M., Lazarowski, E. R., . . . Ravichandran, K. S. (2010). Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. NATURE, 467(7317), 863-U136. doi:10.1038/nature09413

Elliott, M. R., & Ravichandran, K. S. (2010). ELMO1 signaling in apoptotic germ cell clearance and spermatogenesis. CLEARANCE OF DYING CELLS IN HEALTHY AND DISEASED IMMUNE SYSTEMS, 1209, 30-36. doi:10.1111/j.1749-6632.2010.05764.x

Elliott, M. R., Zheng, S., Park, D., Woodson, R. I., Reardon, M. A., Juncadella, I. J., . . . Ravichandran, K. S. (2010). Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo. NATURE, 467(7313), 333-U114. doi:10.1038/nature09356

Kadl, A., Meher, A. K., Sharma, P. R., Lee, M. Y., Doran, A. C., Johnstone, S. R., . . . Leitinger, N. (2010). Identification of a Novel Macrophage Phenotype That Develops in Response to Atherogenic Phospholipids via Nrf2. CIRCULATION RESEARCH, 107(6), 737-U155. doi:10.1161/CIRCRESAHA.109.215715

Elliott, M. R., & Ravichandran, K. S. (2010). Clearance of apoptotic cells: implications in health and disease. JOURNAL OF CELL BIOLOGY, 189(7), 1059-1070. doi:10.1083/jcb.201004096

2009

Elliott, M. R., Chekeni, F. B., Trampont, P. C., Lazarowski, E. R., Kadl, A., Walk, S. F., . . . Ravichandran, K. S. (2009). Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. NATURE, 461(7261), 282-U165. doi:10.1038/nature08296

2008

Elliott, M. R., & Ravichandran, K. S. (2008). Pallbearer and friends: lending a hand in apoptotic cell clearance. TRENDS IN CELL BIOLOGY, 18(3), 95-97. doi:10.1016/j.tcb.2007.12.005

Elliott, M. R., & Ravichandran, K. S. (2008). Death in the CNS: Six-microns-under. CELL, 133(3), 393-395. doi:10.1016/j.cell.2008.04.014

2007

Park, D., Tosello-Trampont, A. -C., Elliott, M. R., Lu, M., Haney, L. B., Ma, Z., . . . Ravichandran, K. S. (2007). BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. NATURE, 450(7168), 430-U10. doi:10.1038/nature06329

2006

Kiss, R. S., Elliott, M. R., Ma, Z., Marcel, Y. L., & Ravichandran, K. S. (2006). Apoptotic cells induce a phosphatidyiserine-dependent homeostatic response from phagocytes. CURRENT BIOLOGY, 16(22), 2252-2258. doi:10.1016/j.cub.2006.09.043