Division of Pulmonary & Critical Care Medicine

Timothy D. Bigby, M.D.

Professor of Medicine

Interim Division Director

Chief, Pulmonary and Critical Care Section

VA San Diego Health Care System

 

INVESTIGATIVE INTERESTS:

Dr. Bigby’s research laboratory has a long-standing interest in inflammatory cell biology, innate immunity in the lung and diseases of the airway.  The current focus is on two groups of receptors of the innate immune system Toll/Interleukin 1 receptor (TIR) domain and NOD proteins, as well as their signaling pathways.  How these receptors and their ligands are regulated and, in turn, modify disease susceptibility and phenotype in the airway are of particular interest.  Specific projects focus on interferon b, the TIR domain receptor T1/ST2 and NOD1 in asthma, COPD, and lung infection.

SELECTED PUBLICATIONS:

  1. Ring WL, Riddick CA, Baker JR, Munafo DA, Bigby TD.  Human monocytes lose 5-lipoxygenase and FLAP as they mature into monocyte-derived macrophages in vitro.  Am. J. Physiol. 271 (Cell Physiol. 40):  C372-C377, 1996.
  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. 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;2:637-646.
  4. Serio KJ, Baker JR, Ring WL, Riddick CA, Bigby TD.  Leukotriene B4 co-stimulates 5-lipoxygenase activity in neutrophils via increased 5-lipoxygenase translocation.  Am. J. Physiol. 272 (Cell Physiol. 41): C1329-1334, 1997.
  5. Riddick CA, Ring WL, Baker JR, Hodulik CR, Bigby TD.  Dexamethasone increases expression of 5-lipoxygenase and its activating protein in human monocytes and THP-1 cells.  Eur. J. Biochem. 246: 112-118, 1997.
  6. Ring WL, Riddick CA, Baker JR, Glass CK, Bigby TD.  Activated lymphocytes increase expression of 5-lipoxygenase and its activating protein in THP-1 cells.  Am. J. Physiol. 273 (Cell Physiol. 42): C2057-C2064, 1997.
  7. Bigby TD, Levy BD, Serhan CN.  Chapter 7.  Cell biology of the 5-lipoxygenase pathway: Amplification and generation of leukotrienes and novel eicosanoids by transcellular biosynthesis.  in Five Lipoxygenase Products in Asthma. Drazen J, Dahlen SE, Lee T eds.  Lung Biology in Health and Disease series, Vol 120. Marcel Dekker, Inc., NY, NY.  pp 125-173, 1998.
  8. 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.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.
  9. Bigby TD.  Perspective.  The leukotriene C4 synthase gene and asthma.  Am. J. Respir. Cell Mol Biol.  23:273-276, 2000.
  10. Bigby TD.  The Yin and the Yang of 5-Lipoxygenase Pathway Activation.  Mol. Pharmacol.  62:200-202, 2002.
  11. 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
  12. 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.
  13. Narsipur SS, Peterson OW, Smith RM, Bigby TD, Parthasarathy S, Gabbai FB, Wilson CB, Blantz RC.  The mechanisms of glomerular immune injury:  Effects of antioxidant treatment.   J. Am. Soc. Nephrol. 14:1748-1755, 2003.
  14. Rhee C-S, Libet L, Chisholm D, Takabayashi K, Baird S, Bigby TD, Lee CH, Horner AA, Raz E.  Allergen independent immunostimulatory sequence oligodeoxynucleotide therapy attenuates experimental allergic rhinitis.  Immunology 113:106-113, 2004.
  15. Serio KJ, Reddy KV, Bigby TD.  Lipopolysaccharide induces 5-lipoxygenase activating protein gene expression in THP-1 cells via a NF-kB and C/EBP-mediated mechanism.  Am. J. Physiol-Cell Physiol, 288: C1125-1133, 2005.
  16. Georgel P, Crozat K, Lauth X, Makrantonaki E, Seltmann H, Sovath S, Hoebe K, Du X, Rutschmann S, Jiang Z, Bigby T, Nizet V, Zouboulis CC, Beutler, B.  A toll-like receptor 2-responsive lipid effector pathway protects mammals against skin infections with gram-positive bacteria.  Infect. Immun.  73: 4512-4521, 2005.
  17. Jiang Z, Georgel P, Li C, Choe J, Crozat K, Rutschmann S, Du X, Bigby T, Mudd S, Sovath S, Wilson IA, Olson A, Beutler B.  Details of toll-like receptor:adapter interaction revealed by germ-line mutagenesis.  Proc. Natl. Acad. Sci. 103:10961-10966, 2006.
  18. White A, Bigby T, Stevenson D.  Intranasal ketorolac challenge for the diagnosis of aspirin-exacerbated respiratory disease.  Ann Allergy Asthma Immunol 97:190-195, 2006
  19. Broderick KE, Balasubramanian M, Chan A, Potluri P, Feala J, McCulloch A, Sharma VS, Pilz RB, Bigby TB, Boss GR.  The cobalamin precursor cobinamide detoxifies nitroprusside-generated cyanide. Exp Biol Med 232:789-798, 2007.
  20. Broderick KE, Alvarez L, Balasubramanian M, Belke DD, Makino A, Chan A, Woods VL, Dillmann WH, Sharma VS, Pilz RB, Bigby TD, Boss GR.  Nitrosyl-cobinamide, a new and direct nitric oxide releasing drug effective in vivo.  Exp Biol Med, 232:1432-1440, 2007.
  21. Broderick KE, Chan A, Balasubramanian M, Feala J, McCulloch A, Reed SL, Panda M, Sharma VS, Pilz RB, Bigby TB, Boss GR.  Cyanide produced by human isolates of Pseudomonas aeruginosa contributes to lethality in Drosophila melanogaster.  J. Infect. Dis., 197:457-464, 2008.
  22. Finn PW, Bigby TD.  Innate immunity and asthma.  Proceedings of the American Thoracic Society 6:260-265, 2009.
  23. Chan A, Mohammad O, Blackledge W, Balasubramanian M, Alvarez L, Boss GR, Bigby TD.  Cobinamide is superior to other treatments in a mouse model of cyanide poisoning.  Clinical Toxicology, 48:709-717, 2010.

PubMed

Board Certified:

  • Internal Medicine
  • Pulmonary Medicine

VA Medical Center

To schedule an appointment with Dr. Bigby, contact 858-642-3541

To contact Dr. Bigby:  tbigby@ucsd.edu