Collaborators

Unit:  Medicine
Department:  Biological Chemistry
Title:  Vincent Massey Collegiate Professor and Associate Head of Biological Chemistry
Phone:  (734) 615-5238
Email:  [email protected]
Expertise:  redox, sulfur, cell signaling, antioxidants, cell stress resistance, inflammation

Unit:  Medicine
Department:  Microbiology and Immunology
Title:  Professor of Microbiology and Immunology
Phone:  (734) 647-6339
Email:  [email protected]
Keywords:  macrophage, cell biology, phagocytosis, lysosomes, endocytosis

Short bio:
Dr. Swanson received his PhD from Princeton University in 1982 following his training in the laboratories of John T. Bonner and D. Lansing Taylor. He conducted postdoctoral research at the Rockefeller University and Columbia College of Physicians and Surgeons in the laboratory of Samuel Silverstein. He joined the Harvard Medical School faculty in 1986 as an Assistant Professor of Anatomy and Cellular Biology. His lab moved to the University of Michigan Medical School in 1996, first in the Department of Anatomy and Cell Biology and later in the Department of Microbiology and Immunology. He has been a Professor of Microbiology and Immunology since 2001.

Research summary:
Dr. Swanson has examined many areas of cell biology related to macrophages, endocytosis and lysosomes. He developed novel experimental methods for analyzing molecular dynamics and physiology inside living cells and applied them to investigate a wide range of questions in cell biology and innate immunity. His research group has concentrated on lysosome biology, the organization of cytoplasm during phagocytosis and the mechanisms of macrophage killing of Listeria. His lab developed novel microscopic methods to measure pH, reactive oxygen intermediates, lysosomal calcium concentrations, lysosome damage, protein-protein interactions by FRET microscopy, the dynamics of small GTPase activities and the magnitude of signals in forming phagosomes. He has published papers on phagocytosis and phagosome trafficking in macrophages.

Recent publications:
Zhang, Y., A. D. Hoppe and J. A. Swanson. 2010. Coordination of Fc receptor signaling regulates cellular commitment to phagocytosis. Proc. Natl. Acad. Sci. U.S.A. 107(45): 19332-19337. PMCID: PMC2984174.

Sander, L.E., M.J. Davis, M.V. Boekschoten, D. Amsen, C.C. Dascher, B. Ryffel, J.A. Swanson, M. Muller and J.M. Blander. 2011. Detection of prokaryotic mRNA signifies microbial viability and promotes immunity. Nature 474: 385-389. PMCID: 3289942.

Feliciano, W. D., S. Yoshida, S. W. Straight and J. A. Swanson. 2011. Coordination of the Rab5 cycle on macropinosomes. Traffic 12, 1911-1922. PMCID: 3213305.

Welliver, T. P., S. L. Chang, J. J. Linderman and J. A. Swanson. 2011. Ruffles limit diffusion in the plasma membrane during macropinosome formation. J. Cell Sci. 124, 4106-4114. PMCID: 3244989.

Welliver, T. P. and J. A. Swanson. 2012. A growth factor signaling cascade confined to circular ruffles in macrophages. Biol. Open 1(8): 754-760. PMCID: in process.

Davis, M. J., B. Gregorka, J. E. Gestwicki and J. A. Swanson. 2012. Inducible renitence limits Listeria monocytogenes escape from vacuoles in macrophages. J. Immunol. 189: 4489-4495. PMCID: in process

Unit:  Medicine
Department:  Internal Medicine
Title: Professor and Interim Chief Division of Pulmonary and Critical Care Medicine University of Michigan Medical Center
Phone:  (734) 764-4554
Email:  [email protected]
Expertise:  Innate immunity, acute lung injury, sepsis

Short bio:
Dr. Standiford is a Professor of Medicine and Interim Chief of the Division of Pulmonary and Critical Care Medicine at the University of Michigan. He recieved his M.D. from Wayne State University in 1984, performed a Internal Medicine Residency and Chief Residency at the University of Minnesota, then completed a Pulmonary and Critical Care Fellowship at the University of Michigan. Dr. Standiford joined the faculty at Michigan in 2001 as an Assistant Professor, rising to the the rank of Professor in 2000. He was named Interim Chief of the Division in 2011 and Director of the Pulmonary T32 Training Grant that same year. Dr. Standiford has had continuous NIH grant funding as Principal Investigator for the past 22 years and served as the Program Director of the University of Michigan SCOR in Acute Lung Injury (2000-2002) and University of Michigan SCCOR in Acute Lung Injury (2003-2009). Dr. Standiford has served as a permanent member of both the NIH Lung Biology and Pathology (LBPA) and Lung Cell and Molecular Immunology (LCMI) Study Sections. He served as a member of the American Lung Association Research Fellowship and Career Investigator Award Committee from 2000-2004, and Chair of this committee from 2004-2009. He is an elected member of the American Society for Clinical Investigation (ASCI) and the Association of American Physicians (AAP). Dr. Standiford’s bibliography lists >200 peer-reviewed publications, of which over 90 manuscripts have been published in the past 10 years.

Research Summary:
The central thrust of studies performed in Dr. Standiford’s laboratory have focused on exploring the role of specific cells, cytokines, antimicrobial peptides and toll like receptors (TLRs) in the generation of protective innate immune responses of the lung. Mouse models of bacterial and viral pneumonia have been developed to discern basic mechanisms of protective pulmonary innate immunity. Gene deletion/transgenic techniques, passive immunization, and gene knockdown approaches have been applied to identify relevant mediators and novel therapeutic approaches. Studies are ongoing to define the effects of viral infection or systemic sepsis on subsequent lung innate antibacterial immune responses, and determine the contribution of inhibitors of TLR signaling cascades to regulation of innate responses. The epigenetic regulation of innate macrophage responses in sepsis and acute lung injury is a focus of both animal and human based translational research. Studies to address mechanisms by which toll like receptors contribute to disease pathogenesis in non-infectious lung injury, including hyperoxic lung injury and bleomycin-induced lung injury, is a new a promising direction of research within the laboratory. In human trials, Dr. Standiford has investigated mechanisms of lung injury in ARDS, which has included the use of discovery based platforms such as metabolomics, gene expresssion array, and genomics. He has led clinical trials assessing the effect of growth factor administration on outcome in ARDS patients and in patients at risk for the development of ARDS.

Recent publications:
Deng JC, Cheng G, Newstead MW, Zeng X, Kobayashi K, Flavell RA, Standiford TJ. Sepsis-induced suppression of lung innate immunity is mediated by IRAK-M. J Clin Invest 2006; 116:2532-42. PMC1550278

Bhan U, Lukacs NW, Osterholzer JJ, Newstead MW, Zeng X, Moore TA, McMillan TR, Krieg AM, Akira S, Standiford TJ. TLR9 is required for protective innate immunity in gram-negative bacterial pneumonia: role of dendritic cells. J Immunol 2007; 179:3937-46.

Reddy RC, Narala VR, Keshamouni VG, Milam JE, Newstead MW, Standiford TJ. Sepsis-induced inhibition of neutrophil chemotaxis is mediated by activation of peroxisome proliferators-activated receptor-g. Blood 2008; 112:4250-4258. PMC2582007

Keshamouni VG, Jagtap P, Michailidis G, Strahler JR, Kuick R, Panagiotis P, Krishnapuram R, Srirangam A, Standiford TJ, Andrews PC, Omenn GS. Temporal quantitative proteomics by iTRAQ 2D-LC-MS/MS and corresponding mRNA expression analysis identify post-transcriptional modulation of actin-cytoskeleton regulators during TGF-b-induced epithelial-mesenchymal transition. J Proteome Res 8:35-47, 2009. PMID: 19118450

Ito T, Schaller M, Hogaboam CM, Standiford TJ, Sandor M, Lukacs NW, Chensue SW, Kunkel SL. TLR9 regulates the mycobacteria-elicited pulmonary granulomatous immune response in mice through DC-derived Notch ligand delta-like 4. J Clin Invest 119:33-46, 2009. PMC2613456

Seki M, Kohno S, Newstead M, Zeng X, Bhan U, Lukacs NW, Kunkel SL, Standiford TJ. Critical role of IRAK-M in regulating chemokine-dependent deleterious inflammation in murine influenza pneumonia. J Immunol 2010; 184:1410-8. PMC2995366

Yu F, Cornicelli MD, Kovach MA, Newstead MW, Zeng X, Kumar A, Gao N, Yoon S, Gallo RL, Standiford TJ. Flagellin stimulates protective lung mucosal immunity: role of cathelicidin related antimicrobial peptide. J. Immunol 185:1142-1149, 2010. PMC3038689

Lyn-Kew K, Rich E, Zeng X, Wen H, Kunkel SL, Newstead MW, Bhan U, Standiford TJ. IRAK-M regulates chromatin remodeling in lung macrophages during experimental sepsis. PLoS One 5: e11145, 2010. PMC2886833

Bhan U, Newstead MJ, Zeng X, Ballinger MN, Standiford LR, Standiford TJ. Stachybotrys chartarum-induced hypersensitivity pneumonitis is TLR9 dependent. Am J Pathol 179:2779-87, 2011. PMCID: PMC3260863

Standiford TJ, Kuick R, Bhan U, Chen J, Newstead M, Keshamouni VG. TGF-b-induced IRAK-M expression in tumor-associated macrophages regulates lung tumor growth.Oncogene 30:2475-84, 2011. PMC3102782

Stringer KA, Serkova NJ, Karnovsky A, Guire K, Paine R 3rd, Standiford TJ. Metabolic consequences of sepsis-induced acute lung injury revealed by plasma 1H-nuclear magnetic resonance quantitative metabolomics and computational analysis. Am J Physiol Lung Cell Mol Physiol 300:L4-L11, 2011. PMC3023293

Paine III R, Standiford TJ, Dechert RE, Moss M, Martin GS, Rosenberg AL, Thannickal VJ, Burnham EL, Brown MB, Hyzy RC. A randomized trial of recombinant human GM-CSF for patients with acute lung injury. Crit Care Med 40:90-70, 2012. PMC3242850

Kovach MA, Ballinger MN, Newstead MW, Zeng X, Bhan U, Yu F, Moore BB, O’Riordan M, Gallo R, Standiford TJ. Cathelicidin related antimicrobial peptide is required for effective lung mucosal immunity in Gram-negative bacterial pneumonia. J Immunol189:304-311, 2012. PMID: 22634613; PubMed in process

Ballinger MN, Newstead MW, Zeng X, Bhan U, Horowitz JC, Moore BB, Pinsky DJ,Standiford TJ. TLR signaling prevents hyperoxia induced lung injury by protecting the alveolar epithelium from oxidant mediated death. J Immunol 189:356-364, 2012. PMID: 22661086 PubMed – in process

Burnham EL; Hyzy RC, Coley C; Kelly AM; Quint LE, Janssen WJ, Moss M, Standiford TJ. Chest high resolution CT features are associated with physical impairment in ALI survivors. CritCare Med (in press).