Mark James Miller, Ph.D.

Associate Professor
Internal Medicine
Infectious Diseases

Immunology Program
Molecular Microbiology and Microbial Pathogenesis Program

  • 314-362-3044

  • 314-362-3176

  • 314-362-4096

  • Room 3710 West Bldg.


  • imaging, inflammation, pathogenesis, mathematical modeling, multi-photon microscopy

  • Lymphoid tissue dynamics and antigen-presentation during infection, cancer and autoimmunity

Research Abstract:

My group is using multi-photon microscopy (MPM) in combination with histological and genetic approaches to study the immune response to bacterial infection in the spleen. The spleen plays a crucial role in host defense by trapping and destroying blood-borne pathogens and triggering the adaptive immune response. However, few details are known regarding how early host-pathogen interactions lead to antigen presentation and immunity. Preliminary results from my lab indicate that bacterial challenge in mice induces the rapid redistribution of splenic macrophages and dendritic cells in a bacteria-specific fashion. Our hypothesis is that tissue remodeling serves an “antigen transport” function that delivers pathogen-derived antigens to distinct microenvironments for presentation. Because both the antigen presenting cell type and the local environment impact the immune response, this could provide a mechanism to tailor immune responses to a wide-range of pathogens. We are focusing our investigations on three key stages of infection: 1) the initial capture and fate of bacteria in marginal zone macrophages and dendritic cells, 2) the migration of these cells in response to infection, and 3) bacterial-antigen presentation in tissue microenvironments and its influence on the subsequent adaptive immune response. Moreover, the multi-dimensional cell tracking data from these studies is being used to create in silico models of infection and immunity in the hope of providing fresh mechanistic insight into microbial pathogenesis and guide vaccine development.

Selected Publications:

Okada T, Miller MJ, Parker I, Krummel MF, Neighbors M, Hartley SB, O'Garra A, Cahalan MD, Cyster JG. Antigen-engaged B cells undergo chemotaxis toward the T zone and form motile conjugates with helper T cells. PLoS Biol 2005 3:e150 (Epub 2005 May 3).

Miller MJ, Safrina O, Parker I, Cahalan MD. Imaging the single cell dynamics of CD4+ T cell activation by dendritic cells in lymph nodes. J Exp Med 2004 200:847-856.

Miller MJ, Hejazi AS, Wei SH, Cahalan MD, Parker I. T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph node. Proc Natl Acad Sci USA 2004 101:998-1003 (Epub 2004 Jan 13).

Miller MJ, Wei SH, Cahalan MD, Parker I. Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy. Proc Natl Acad Sci USA 2003 100:2604-2609 (Epub 2003 Feb 24).

Miller MJ, Wei SH, Parker I, Cahalan MD. Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 2002 7:296:1869-1873 (Epub 2002 May 16).

Last Updated: 8/4/2011 11:01:06 AM

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