Edward Miao, M.D./Ph.D.

I have extensive experience studying the interaction of macrophages and bacterial pathogens, having performed research in these fields since 1996, with particular focus on S. typhimurium virulence factors and the innate immune response to these virulence factors.  I showed that flagellin and type III secretion system rod proteins are detected by macrophages in the cytosolic compartment.  My understanding of both macrophage biology as well as the microbial factors required for pathogenesis makes me ideally suited to examine the interaction between these two fields with application to S. typhimurium.  I have participated in co-mentoring a graduate student and an infectious disease fellow with Dr. Aderem, resulting in 5 co-senior author papers, and have experience supervising technicians in Dr. Aderem’s lab.  In addition, I also have medical training that will help me place the results of these studies in a biological context.  I started my independent lab as an Assistant Professor in the Department of Microbiology and Immunology in the University of North Carolina at Chapel Hill in September 1, 2011.  Since then, I have extablished a vibrant laboratory with three post docs and three graduate students.  The first manuscript from my independent group was published in February 2013 in Science.

Assistant Professor
 

Positions and Employment

2004-2011  Postdoctoral Fellow / Research Scientist,

with Alan Aderem, PhD
Institute for Systems Biology, Seattle, WA

 

2011-present Assistant Professor,

Department of Microbiology and Immunology,
University of North Carolina at Chapel Hill, Chapel Hill, NC

 

2012-present Associate Member, Lineberger Comprehensive Cancer Center
University of North Carolina at Chapel Hill, Chapel Hill, NC

Academic and Professional Honors

1993  Howard Hughes Summer Honors Advanced Research Program
1997-2000  Poncin Scholarship
2000  Helen Riaboff Whitely Endowed Fellowship Award
2000-2002  Paul Allen Foundation Fellowship Award

Graduate work.  My interest in the host-pathogen interaction is long standing, beginning in my Ph.D. thesis where I focused on pathogen virulence factors.  Working with Sam Miller at the University of Washington, I identified and characterized a group of seven T3SS effector proteins in Salmonella typhimurium and characterized the interaction of one of these effectors with host cytoskeletal proteins. 


Medical training.  At the University of Washington, I was enrolled in a joint M.D./Ph.D. degree program, and finished the last two years of the M.D. training after my Ph.D.  I focused my elective studies learning about infectious disease, allergy, rheumatology and autoimmunity. At the end of my training I decided to focus on research, and thus, rather than entering residency training, I returned to the lab.


Postdoctoral research.  My interests shifted towards the innate immune side of the host pathogen interaction in my post-doctoral work with Alan Aderem at the Institute for Systems Biology.  I began to study the mechanisms whereby macrophages detect bacterial virulence factors, including the aforementioned T3SS, and the responses that this detection evokes through caspase 1 signaling, detailed below. 


Mentoring and supervisory experience.  I recent years I have had the opportunity to serve as co-mentor to a graduate student in the lab, Sarah Warren, as she investigates caspase 1 detection of Listeria. I also began co-mentoring an infectious disease fellow in the lab, Dr. Jayant Rajan, who is investigating viral detection via caspase 1. This co-mentorship is formally acknowledged by a co-senior authorship with Dr. Alan Aderem on their published and submitted manuscripts (see CV).  I also supervise two technicians.  This experience of managing a semi-independent group with four members within the Aderem Lab will serve me well when starting up a group de novo. 

PUBLICATIONS

  1. Aachoui, Y., I.A. Leaf, J.A.Hagar, M.F. Fontana, C.G. Campos, D.E. Zak, M.H. Tan, P.A. Cotter, R.E. Vance, A. Aderem, and E.A. Miao,  Caspase-11 protects against bacteria that escape the vacuole. Science.  339, pp. 975-978, 2013. 
  2. Rayamajhi, M., and E.A. Miao, Just say NO to NLRP3. Nat Immunology, 14: p. 12-14, 2013. Invited News and Views.
  3. Jørgensen, I., and E.A. Miao, YopM puts Caspase-1 on ice.  Cell Host and Microbe, 14: p. 12-14, 2012. Invited Preview.
  4. Rayamajhi, M., H. Zhang and E.A. Miao, Methods to examine pyroptotic cell death. The Inflammasome Protocols Book.  2012.  Invited methods paper.  In press.
  5. Inoue, M., K.L. Williams, T. Oliver, P. Vandenabeele, J.V. Rajan, E.A. Miao, and M.L. Shinohara, Interferon-beta Therapy Against EAE Is Effective Only When Development of the Disease Depends on the NLRP3 Inflammasome. Sci Signal, 5(225): p. ra38, 2012.
  6. Miao, E.A., J.V. Rajan, and A. Aderem, Caspase-1 induced pyroptotic cell death. Immunol Rev. 243: p. 206-214, 2011. Invited review 
  7. Miao, E.A. and J.V. Rajan, Salmonella and Caspase-1: a complex interplay of detection and evasion. Front Micro, 2 acticle 85: p. 1-6, 2011. Invited Review
  8. Warren, S.E., H. Duong, D.P. Mao, A. Armstrong, J. Rajan, E.A. Miao†, and A. Aderem†, Generation of a Listeria vaccine strain by enhanced caspase-1 activation. Eur J Immunol, 41(7): p. 1934-40, 2011. †  Miao and Aderem share senior authorship.
  9. Rajan, J.V., D. Rodriguez, E.A. Miao†, and A. Aderem†, The NLRP3 Inflammasome Detects Encephalomyocarditis Virus and Vesicular Stomatitis Virus Infection. J Virol, 85(9): p. 4167-72, 2011.†  Miao and Aderem share senior authorship.
  10. Lightfield, K.L., J. Persson, N.J. Trinidad, S.W. Brubaker, E.M. Kofoed, J.D. Sauer, E.A. Dunipace, S.E. Warren, E.A. Miao, and R.E. Vance, Differential requirements for NAIP5 in activation of the NLRC4 inflammasome. Infect Immun, 79(4): p. 1606-14, 2011.
  11. Miao, E.A., I.A. Leaf, P.M. Treuting, D.P. Mao, M. Dors, A. Sarkar, S.E. Warren, M.D. Wewers, and A. Aderem, Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Nat Immunol, 2010. 11(12): p. 1136-42. [*  This article was selected for the journal cover illustration. #  This article was selected by the Faculty of 1000 as one of the Top 7 papers in Immunolgoy in the January 2011 issue of The Scientist. §  Also see commentary: Brodsky, I.E. and R. Medzhitov, Pyroptosis: macrophage suicide exposes hidden invaders. Curr Biol, 21(2): p. R72-5, 2011.]
  12. Miao, E.A., D.P. Mao, N. Yudkovsky, R. Bonneau, C.G. Lorang, S.E. Warren, I.A. Leaf, and A. Aderem, Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. Proc Natl Acad Sci U S A, 107(7): p. 3076-80, 2010. 
  13. Miao, E.A. and S.E. Warren, Innate immune detection of bacterial virulence factors via the NLRC4 inflammasome. J Clin Immunol, 30(4): p. 502-6, 2010. Invited review 
  14. Warren, S.E., A. Armstrong, M.K. Hamilton, D.P. Mao, I.A. Leaf, E.A. Miao†, and A. Aderem†, Cutting edge: Cytosolic bacterial DNA activates the inflammasome via Aim2. J Immunol, 185(2): p. 818-21, 2010. †  Miao and Aderem share senior authorship.
  15. Rajan, J.V., S.E. Warren, E.A. Miao†, and A. Aderem†, Activation of the NLRP3 inflammasome by intracellular poly I:C. FEBS Lett, 584(22): p. 4627-32, 2010.†  Miao and Aderem share senior authorship.
  16. Shimada, T., B.G. Park, A.J. Wolf, C. Brikos, H.S. Goodridge, C.A. Becker, C.N. Reyes, E.A. Miao, A. Aderem, F. Gotz, G.Y. Liu, and D.M. Underhill, Staphylococcus aureus evades lysozyme-based peptidoglycan digestion that links phagocytosis, inflammasome activation, and IL-1beta secretion. Cell Host Microbe, 7(1): p. 38-49, 2010.
  17. Di Paolo, N.C., E.A. Miao, Y. Iwakura, K. Murali-Krishna, A. Aderem, R.A. Flavell, T. Papayannopoulou, and D.M. Shayakhmetov, Virus binding to a plasma membrane receptor triggers interleukin-1 alpha-mediated proinflammatory macrophage response in vivo. Immunity, 31(1): p. 110-21, 2009.
  18. Warren, S.E., D.P. Mao, A.E. Rodriguez, E.A. Miao†, and A. Aderem†, Multiple Nod-like receptors activate caspase 1 during Listeria monocytogenes infection. J Immunol, 180(11): p. 7558-64, 2008. †  Miao and Aderem share senior authorship.
  19. Miao, E.A., R.K. Ernst, M. Dors, D.P. Mao, and A. Aderem, Pseudomonas aeruginosa activates caspase 1 through Ipaf. Proc Natl Acad Sci U S A, 105(7): p. 2562-7, 2008.
  20. Miao, E.A., E. Andersen-Nissen, S.E. Warren, and A. Aderem, TLR5 and Ipaf: dual sensors of bacterial flagellin in the innate immune system. Semin Immunopathol, 29(3): p. 275-88, 2007. Invited review 
  21. Miao, E.A., C.M. Alpuche-Aranda, M. Dors, A.E. Clark, M.W. Bader, S.I. Miller, and A. Aderem, Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf. Nat Immunol, 7(6): p. 569-75, 2006. § Also see accompanying News and Views: Roy, C.R. and D.S. Zamboni, Cytosolic detection of flagellin: a deadly twist. Nat Immunol, 7(6): p. 549-51, 2006..