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Elliott, Michael

Michael Elliott

Primary Appointment

Microbiology, Immunology, and Cancer Biology

Contact Information

Telephone: 434.982.3227
Email: mre4n@virginia.edu

Research Interests

Macrophage effector functions in inflammation and immunotherapy

Research Description

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.

Selected Publications

Arandjelovic S, Perry JSA, Lucas CD, Penberthy KK, Kim TH, Zhou M, Rosen DA, Chuang TY, Bettina AM, Shankman LS, Cohen AH, Gaultier A, Conrads TP, Kim M, Elliott MR, Ravichandran KS, A noncanonical role for the engulfment gene ELMO1 in neutrophils that promotes inflammatory arthritis., 2019; Nature immunology. 20(2) 141-151 PMID: 30643265 | PMCID: PMC6402828

Moon TJ, Elliott MR, Measuring Leukocyte Migration to Nucleotides., 2019; Methods in molecular biology (Clifton, N.J.). 2041() 345-349 PMID: 31646502 |

Frisch BJ, Hoffman CM, Latchney SE, LaMere MW, Myers J, Ashton J, Li AJ, Saunders J, Palis J, Perkins AS, McCabe A, Smith JN, McGrath KE, Rivera-Escalera F, McDavid A, Liesveld JL, Korshunov VA, Elliott MR, MacNamara KC, Becker MW, Calvi LM, Aged marrow macrophages expand platelet-biased hematopoietic stem cells via Interleukin1B., 2019; JCI insight. 5() PMID: 30998506 | PMCID: PMC6542605

Hilt ZT, Pariser DN, Ture SK, Mohan A, Quijada P, Asante AA, Cameron SJ, Sterling JA, Merkel AR, Johanson AL, Jenkins JL, Small EM, McGrath KE, Palis J, Elliott MR, Morrell CN, Platelet-derived ?2M regulates monocyte inflammatory responses., 2019; JCI insight. 4(5) PMID: 30702442 | PMCID: PMC6483513

Safronova A, Araujo A, Camanzo ET, Moon TJ, Elliott MR, Beiting DP, Yarovinsky F, Alarmin S100A11 initiates a chemokine response to the human pathogen Toxoplasma gondii., 2018; Nature immunology. 20(1) 64-72 PMID: 30455460 | PMCID: PMC6291348

Bhagwat SP, Gigliotti F, Wang J, Wang Z, Notter RH, Murphy PS, Rivera-Escalera F, Malone J, Jordan MB, Elliott MR, Wright TW, Intrinsic Programming of Alveolar Macrophages for Protective Antifungal Innate Immunity Against Pneumocystis Infection., 2018; Frontiers in immunology. 9() 2131 PMID: 30283457 | PMCID: PMC6156154

VanDerMeid KR, Elliott MR, Baran AM, Barr PM, Chu CC, Zent CS, Cellular Cytotoxicity of Next-Generation CD20 Monoclonal Antibodies., 2018; Cancer immunology research. 6(10) 1150-1160 PMID: 30089638 |

Murphy PS, Wang J, Bhagwat SP, Munger JC, Janssen WJ, Wright TW, Elliott MR, CD73 regulates anti-inflammatory signaling between apoptotic cells and endotoxin-conditioned tissue macrophages., 2017; Cell death and differentiation. 24(3) 559-570 PMID: 28060378 | PMCID: PMC5344214

Zent CS, Elliott MR, Maxed out macs: physiologic cell clearance as a function of macrophage phagocytic capacity., 2016; The FEBS journal. 284(7) 1021-1039 PMID: 27863012 | PMCID: PMC5378628

Stevenson C, de la Rosa G, Anderson CS, Murphy PS, Capece T, Kim M, Elliott MR, Essential role of Elmo1 in Dock2-dependent lymphocyte migration., 2014; Journal of immunology (Baltimore, Md. : 1950). 192(12) 6062-70 PMID: 24821968 | PMCID: PMC4127066

Lu Z, Elliott MR, Chen Y, Walsh JT, Klibanov AL, Ravichandran KS, Kipnis J, Phagocytic activity of neuronal progenitors regulates adult neurogenesis., 2011; Nature cell biology. 13(9) 1076-83 PMID: 21804544 | PMCID: PMC3374401

Park D, Han CZ, Elliott MR, Kinchen JM, Trampont PC, Das S, Collins S, Lysiak JJ, Hoehn KL, Ravichandran KS, Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein., 2011; Nature. 477(7363) 220-4 PMID: 21857682 | PMCID: PMC3513690

Chekeni FB, Elliott MR, Sandilos JK, Walk SF, Kinchen JM, Lazarowski ER, Armstrong AJ, Penuela S, Laird DW, Salvesen GS, Isakson BE, Bayliss DA, Ravichandran KS, Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis., 2010; Nature. 467(7317) 863-7 PMID: 20944749 | PMCID: PMC3006164

Elliott MR, Zheng S, Park D, Woodson RI, Reardon MA, Juncadella IJ, Kinchen JM, Zhang J, Lysiak JJ, Ravichandran KS, Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo., 2010; Nature. 467(7313) 333-7 PMID: 20844538 | PMCID: PMC3773546

Kadl A, Meher AK, Sharma PR, Lee MY, Doran AC, Johnstone SR, Elliott MR, Gruber F, Han J, Chen W, Kensler T, Ravichandran KS, Isakson BE, Wamhoff BR, Leitinger N, Identification of a novel macrophage phenotype that develops in response to atherogenic phospholipids via Nrf2., 2010; Circulation research. 107(6) 737-46 PMID: 20651288 | PMCID: PMC2941538

Elliott MR, Ravichandran KS, Clearance of apoptotic cells: implications in health and disease., 2010; The Journal of cell biology. 189(7) 1059-70 PMID: 20584912 | PMCID: PMC2894449

Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF, Park D, Woodson RI, Ostankovich M, Sharma P, Lysiak JJ, Harden TK, Leitinger N, Ravichandran KS, Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance., 2009; Nature. 461(7261) 282-6 PMID: 19741708 | PMCID: PMC2851546

Park D, Tosello-Trampont AC, Elliott MR, Lu M, Haney LB, Ma Z, Klibanov AL, Mandell JW, Ravichandran KS, BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module., 2007; Nature. 450(7168) 430-4 PMID: 17960134 |