Timothy D. Bigby, MD

Professor of Medicine Chief Pulmonary, and Critical Care Section VA San Diego Health Care System

RESEARCH INTERESTS:

Airway inflammation and lipid mediator pathways involved in diseases of the airway. We focus primarily on the 5-lipoxygenase pathway of arachidonic acid metabolism, the regulation of expression of the enzymes of this pathway, and how these enzymes might be over-expressed in diseases such as asthma, chronic obstructive pulmonary disease, and bronchogenic carcinoma of the lung. We have determined that lymphocyte-derived cytokines, glucocorticoids, and ligands for receptors involved in innate immunity play a major role in regulation of expression of these enzymes. We are currently exploring the molecular mechanisms of regulation of expression and determining the role of single nucleotide polymorphisms in the regulatory elements of the corresponding genes in airway disease phenotypes. A new area of investigation focuseson the role of the innate immune system in the pathogenesis of airway and interstitial lung diseases.

SELECTED PUBLICATIONS:

1. Bigby TD, Hodulik CR, Arden KC, Fu L. Molecular cloning of the human leukotriene C4 synthase gene and assignment to chromosome 5q35. Mol Med 1996;2:637-46.
2. Ring WL, Riddick CA, Baker JR, Munafo DA, Bigby TD. Lymphocytes stimulate expression of 5-lipoxygenase and its activating protein in monocytes in vitro via granulocyte-macrophage colony stimulating factor and interleukin-3. J. Clin. Invest. 97:1293-1301, 1996.
3. Riddick CA, Ring WL, Baker JR, Bigby TD. Dexamethasone enhances expression of 5-lipoxygenase and its activating protein in mononuclear phagocytes. Eur J Biochem 1997;246:112-8.
4. Riddick CA, Serio KJ, Hodulik DJ, Regan MS, Ring WL, Bigby TD. Transforming growth factor increases leukotriene C4 synthase expression in the monocyte-like cell line, THP-1. J Immunol 1999;62:1101-7.
5. Riddick CA, Serio KJ, Hodulik DJ, Regan MS, Ring WL, Bigby TD. Transforming growth factor b increases leukotriene C4 synthase expression in the monocyte-like cell line, THP-1. J. Immunol. 162:1101-1107, 1999
6. Serio KJ, Hodulik CR, Bigby TD. Sp1 and Sp3 function as key regulators of leukotriene C4 synthase gene expression in the monocyte-like cell line, THP-1. Am. J. Respir. Cell Mol. Biol. 23:234-240, 2000.
7. Serio KJ, Johns SC, Luo L, Hodulik CR, Bigby TD. Lipopolysaccharide downregulates the leukotriene C4 synthase gene in the monocyte-like cell line, THP-1. J. Immunol. 170:2121-2128, 2003
8. Reddy KV, Serio KJ, Hodulik CR, Bigby TD. 5-Lipoxygenase activating protein gene expression: key role of CCAAT/enhancer binding proteins (C/EBP) in constitutive and TNFa-induced expression in THP-1 cells. J. Biol. Chem. 278:13810-13818, 2003

PubMed

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  Internal Medicine

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