Mark M. Davis

Administrative Appointments

• The Burt and Marion Avery Family Professor of Immunology, Stanford University School of Medicine (2007 - present)
• Director, Stanford Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine (2004 - present)
• Chair, Stanford University School of Medicine - Microbiology & Immunology (2002 - 2004)

Honors and Awards

• Milton and Francis Clauser Doctoral Prize, Caltech (1981)
• Passano Young Scientist Award, Passano Foundation (1985)
• Eli Lilly Award in Microbiology and Immunology, American Society of Microbiology (1986)
• Howard Taylor Ricketts Award, University of Chicago (1988)
• Gairdner Prize, Gairdner Foundation (1989)

Professional Education

Postdoctoral Advisees

Klas Erik Petter Brodin,  David Furman,  Ofir Goldberger,  Arnold Han,  Huang Huang,  Jun Huang,  William O'Gorman,  Fleur Tynan,  Feng Wang,  Fei Wen

Graduate & Fellowship Program Affiliations

• Biophysics
• Immunology
• Microbiology and Immunology

Internet Links

• My lab site

Current Research Interests

We are interested in the molecular basis of T and B lymphocyte recognition, as well as the control of differentiation and functional responses in these cells. In particular, we have studied the biochemical basis of T cell receptor binding to antigen/MHC complexes and find that the strength of the interactions is a very good predictor of what the resulting T cell response will be. We also find that T cell receptor-peptide/ MHC complexes have an inherent ability to form oligomers and that this could be part of the ‘trigger’ for T cell activation. One spin-off of these biochemical studies has been the development of tetrameric peptide/MHC reagents which have proven to be generally useful for staining and characterizing antigen-specific T cells in complex mixtures of lymphocytes (i.e. McMichael and Callaghan, J. Exp. Med., 187:1367-1371, 1998). Among other things, we have used these tetramers to follow tumor specific T cells in patients with Melanoma and other cancers. In one patient where we see a substantial number of CD8+ T cells specific for a tumor antigen, the cells have no cytolytic activity and thus seem to have been ‘anergized’ by the tumor. We are now working with a number of groups that have developed different vaccination strategies to determine which strategies are best able to produce a useful response.

Another important aspect of T cell recognition that is something of a ‘black box’ is the mystery of what actually happens on the surface of T cell while it is surveying an antigen presenting cell. To investigate this we have made a large series of green fluorescent protein tagged cell surface molecules, expressed them in B or T lymphocytes and followed their movements using multi-color video microscopy. Thus far we find that many key molecules (ICAM-1, CD48, class II, MHC) on the B cell cluster to the interface with a T cell within seconds after the first rise in internal calcium (in the T cell) and the corresponding movement of complimentary membrane molecules on the T cell may be a key factor in the phenomenon of co-stimulation. That is, the augmentation of T cell responses that is characteristic of responses triggered in T cells when B cells, dendritic cells, or macrophages are the antigen presenting cells. Some of these videos can be seen at http://cmgm.stanford.edu/hhmi/mdavis.

Another area of interest is the structural basis of T cell receptor or antibody binding to their respective antigen/MHC or antigenic ligands. For some years we have noted the extreme sequence diversity in the V(D)-J regions of T cell receptors (the CDR3 loops) and proposed that these sequences are primarily responsible for peptide recognition. Recent X-ray structural analysis and other studies support this contention and suggest that the equivalent diverse CDR3 loops in immunoglobulins also play a key role in specificity determination.

Clinical Trials

• Responses to Influenza Vaccine in Patients with Mitochondrial Disorders (MELAS) Recruiting
• Study of Age-Related Immune Responses to the Shingles Vaccine and Varicella Zoster Virus Recruiting
• B-cell Immunity to Influenza Active, not recruiting
• Comparison of Clonal B-cell Responses to Influenza Vaccine Completed
• Comparison of Immune Responses to Influenza Vaccine In Adults of Different Ages No longer recruiting

Publications

• Cytometry by Time-of-Flight Shows Combinatorial Cytokine Expression and Virus-Specific Cell Niches within a Continuum of CD8(+) T Cell Phenotypes. Newell EW, Sigal N, Bendall SC, Nolan GP, Davis MM. Immunity. 2012
• High-throughput, high-fidelity HLA genotyping with deep sequencing. Wang C, Krishnakumar S, Wilhelmy J, Babrzadeh F, Stepanyan L, Su LF, Levinson D, Fernandez-Viña MA, Davis RW, Davis MM, Mindrinos M. Proc Natl Acad Sci U S A. 2012
• Immunology taught by humans. Davis MM, Sci Transl Med. 2012; 4 (117): 117fs2
• Significance analysis of xMap cytokine bead arrays. Won JH, Goldberger O, Shen-Orr SS, Davis MM, Olshen RA. Proc Natl Acad Sci U S A. 2012
• CD4+ T-cell synapses involve multiple distinct stages. Ueda H, Morphew MK, McIntosh JR, Davis MM. Proc Natl Acad Sci U S A. 2011; 108 (41): 17099-104