David B. Lewis

Clinical Focus

• Infectious Diseases, Pediatric
• Pediatric Infectious Disease

Administrative Appointments

• Director of the Jeffrey Modell Primary Immunodeficiency Center at Stanford, Supported by the Jeffrey Modell Foundation and the Lucile Packard Fund of Children's Health (2002 - present)

Honors and Awards

• Henry J. Kaiser Award for Excellence in Preclinical Teaching (Immunology), Kaiser Foundation (2005)
• Henry J. Kaiser Award for Excellence in Preclinical Teaching (Immunology), Kaiser Foundation (2001)

Professional Education

Postdoctoral Advisees

Crystal Botham , Minna Koskenvuo

Graduate & Fellowship Program Affiliations

• Immunology
• Infectious Diseases
• Pediatrics
• Neonatology and Developmental Biology

Web Site Links

• Lewis Lab Website

Industry Relationships

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Current Research Interests

A long-standing interest is to understand the cellular and molecular basis for this vulnerability of the human neonate to infection with intracellular pathogens that require T helper 1 (Th1) cells [CD4 T cell producing interferon-gamma (IFN-gamma)] for effective immune control. We have previously shown that CD4 T cells of the newborn have a unique limitation in the ability to produce certain effector molecules, such as CD40-ligand (CD154) and IFN-gamma compared to these cells in adults due to both reduced gene transcriptional and impaired signals that lead to gene transcription. Recently, we have shown that these limitations apply to physiological T-cell activation, e.g., using allogeneic dendritic cells. Defining the molecular mechanisms for decreased IFN-gamma production by neonatal CD4 T cells is a current focus.
We have also found that recent thymic emigrants, which predominate in the newborn and young infant, are less able to differentiate into T helper 1 cells, which produce IFN-gamma. These studies required the development of a novel marker for recent thymic emigrants (RTEs) of the CD4 T-cell lineage in humans. Using a combination of approaches, we have identified protein tyrosine kinase 7 (PTK7) as such a marker. In progress are to studies to define the role of PTK7, an orphan member (no known ligand) of the receptor tyrosine kinase family, in T-cell development and immunity, and to determine how this marker can be used to follow the output of recent thymic emigrants in health and disease. We are also interesed in determining the molecular mechanisms for the reduced RTE function and to what extent these mechanisms are shared by neonatal CD4 T cells and CD4+CD8-CD3+ thymocytes, the immediate precursors of antigenically naive CD4 T cells.
We have also found that limitations in T-cell immunogenicity to viruses and viral vaccines extend beyond the neonatal period to childhood. These studies highlight a need to develop more potent vaccines to overcome developmental...

Publications

• Cationic lipid/DNA complexes (JVRS-100) combined with influenza vaccine (Fluzone) increases antibody response, cellular immunity, and antigenically drifted protection. Lay M, Callejo B, Chang S, Hong DK, Lewis DB, Carroll TD, Matzinger S, Fritts L, Miller CJ, Warner JF, Liang L, Fairman J. Vaccine. 2009; 27 (29): 3811-20
• Human CD4+ T cell recent thymic emigrants are identified by protein tyrosine kinase 7 and have reduced immune function. Haines CJ, Giffon TD, Lu LS, Lu X, Tessier-Lavigne M, Ross DT, Lewis DB. J Exp Med. 2009; 206 (2): 275-85
• A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity. Matute JD, Arias AA, Wright NA, Wrobel I, Waterhouse CC, Li XJ, Marchal CC, Stull ND, Lewis DB, Steele M, Kellner JD, Yu W, Meroueh SO, Nauseef WM, Dinauer MC. Blood. 2009; 114 (15): 3309-15
• Efficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells. Zheng J, Liu Y, Qin G, Chan PL, Mao H, Lam KT, Lewis DB, Lau YL, Tu W. J Immunol. 2009; 183 (6): 3742-50
• Asymmetric dimethylarginine and cardiac allograft vasculopathy progression: modulation by sirolimus. Potena L, Fearon WF, Sydow K, Holweg C, Luikart H, Chin C, Weisshaar D, Mocarski ES, Lewis DB, Valantine HA, Cooke JP. Transplantation. 2008; 85 (6): 827-33