Peter Newburger, M.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Cancer Biology
   Pediatrics

Other Affiliation(s):
   Center for AIDS Research
   Interdisciplinary Graduate Program
   Program in Immunology and Virology

Molecular basis of phagocyte function and selenoprotein biosynthesis

Neutrophils provide the first line of host defense against microbial infections and play a major role in inflammation and tissue damage.  Previous studies of RNA expression in neutrophils have revealed a remarkably vigorous transcriptional response to activation by various stimuli, including changes in expression of a large number of transcription factors.  We are now pursuing a coordinated and comprehensive investigation of the transcribed regions and the regulators of transcriptional activity in developing and mature neutrophils. Studies include the identification of “novel” transcripts using tiling arrays, investigation of transcription factors and their promoter sequence targets, testing the roles of Chromatin structure and remodeling proteins in neutrophil activation and differentiation, and exploring changes in the sites of cytosine methylation in activated neutrophils. Identification of novel neutrophil-specific genes and regulatory networks could provide new targets for augmentation of host defense in cancer patients and for attenuation of inflammatory disorders.

1. Another group in our laboratory studies the molecular biology of selenium, an anti-carcinogenic micronutrient. Selenoproteins incorporate the unusual amino acid selenocysteine at a UGA codon.  Our studies of selenoprotein translation examine the RNA-binding proteins that direct selenocysteine incorporation rather than termination at this “stop” codon.   The results should provide new insight into the molecular mechanisms by which selenium nutrition controls the synthesis of these unusual but important proteins and help provide a molecular basis for the anti-carcinogenic effects of dietary selenium.

Recent Publications

Kluger Y, Tuck DP, Chang JT, Nakayama Y, Poddar R, Kohya N, Lian Z, Ben Nasr A, Halaban HR, Krause DS, Zhang X, Newburger PE, Weissman SM.  Lineage specificity of gene expression patterns. Proc Natl Acad Sci U S A. 2004;101:6508-13.

Zhang X, Kluger Y, Nakayama Y, Poddar R, Whitney C, DeTora A, Weissman SM, Newburger PE. Gene expression in mature neutrophils: early responses to inflammatory stimuli. J Leukoc Biol. 2004;75:358-72.

Lian Z, Kluger Y, Greenbaum DS, Tuck D, Gerstein M, Berliner N, Weissman SM, Newburger PE. Genomic and proteomic analysis of the myeloid differentiation program: global analysis of gene expression during induced differentiation in the MPRO cell line. Blood. 2002;100:3209-20.

Lian Z, Wang L, Yamaga S, Bonds W, Beazer-Barclay Y, Kluger Y, Gerstein M, Newburger PE, Berliner N, Weissman SM.  Genomic and proteomic analysis of the myeloid differentiation program. Blood. 2001;98:513-24.

Condino-Neto A, Newburger PE.  Interferon-gamma improves splicing efficiency of CYBB gene transcripts in an interferon-responsive variant of chronic granulomatous disease due to a splice site consensus region mutation. Blood. 2000;95:3548-54.

Shen Q, Wu R, Leonard JL, Newburger PE.  Identification and molecular cloning of a human selenocysteine insertion sequence-binding protein. A bifunctional role for DNA-binding protein B. J Biol Chem. 1998;273:5443-6.

Potential Rotation Projects

1. Determine the pattern and molecular mechanism for the regulated expression of a specific gene during inflammatory stimulation of neutrophils.
2. From differentially-regulated ESTs, determine the full cDNA sequence, predicted amino acid sequence, and inferred protein structure/function.
3. Identify cellular protein(s) that interact structurally and functionally with the selenocysteine translation complex.

Academic Background

M.D. (1974), Harvard Medical School

Keywords: Immunology, Gene Expression

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