Jeffrey D. Laskin
Professor

Cancer research. oncogene expression and growth factor mediated signal transduction. tyrosine kinases. immunobiology of inflammation. nitric oxide

Our research is focused on understanding cellular and molecular mechanisms of growth factor mediated signal transduction in tumor cells. Of particular interest to the laboratory are the receptors for epidermal growth factor (EGF). platelet activating factor (PAF). and gamma interferon. Efforts are in progress to identify transcription factors that are tyrosine phosphorylated by these receptors. Another important area of study in the laboratory is centered on the recently discovered signalling molecule. nitric oxide. Important in cell-cell signalling in a variety of physiological processes. efforts are underway to understand the mechanisms regulating its production by mammalian cells. Growth factors have been identified as a major regulator of nitric oxide production. The role of nitric in cellular nitric oxide production are under investigation. The laboratory has discovered that the bone marrow has the capacity to produce large amounts of nitric oxide in response to inflammatory mediators and several bone marrow growth factors including macrophage colony stimulating factor. interleukin-3 and granulocyte-macrophage colony stimulating factor. These cytokines are used clinically to stimulate immune cell development in the bone marrow in cancer and transplantation patients. Nitric oxide production reduces bone marrow cell growth and antagonizes the effectiveness of these colony stimulating factors. Identifying the bone marrow cell populations producing nitric oxide and the mechanisms by which the cytokine receptors are coupled to the nitric oxide synthetic machinery within these cells are major questions currently being addressed in the laboratory.

Selected Publications

Weinberger B, Quizon C, Vetrano AM, Archer F, Laskin JD, Laskin DL. (2008) Mechanisms mediating reduced responsiveness of neonatal neutrophils to Lipoxin A4. Pediatr Res. Jun 4. [Epub ahead of print]

Chen LC, Laskin JD, Gordon MK, Laskin DL. (2008) Regulation of TREM expression in hepatic macrophages and endothelial cells during acute endotoxemia. Exp Mol Pathol. 84(2):145-55.

Fakhrzadeh L, Laskin JD, Laskin DL. (2008) Regulation of caveolin-1 expression, nitric oxide production and tissue injury by tumor necrosis factor-alpha following ozone inhalation.
Toxicol Appl Pharmacol. 227(3):380-9.

Wang Y, Gray JP, Mishin V, Heck DE, Laskin DL, Laskin JD. (2008) Role of cytochrome P450 reductase in nitrofurantoin-induced redox cycling and cytotoxicity. Free Radic Biol Med. 44(6):1169-79.

Chen LC, Gordon RE, Laskin JD, Laskin DL. (2007) Role of TLR-4 in liver macrophage and endothelial cell responsiveness during acute endotoxemia. Exp Mol Pathol. 83(3):311-26.

Black AT, Gray JP, Shakarjian MP, Laskin DL, Heck DE, Laskin JD. (2008) Distinct effects of ultraviolet B light on antioxidant expression in undifferentiated and differentiated mouse keratinocytes. Carcinogenesis. 29(1):219-25.

Sunil VR, Laumbach RJ, Patel KJ, Turpin BJ, Lim HJ, Kipen HM, Laskin JD, Laskin DL. (2007)
Pulmonary effects of inhaled limonene ozone reaction products in elderly rats. Toxicol Appl Pharmacol. 222(2):211-20.

Sunil VR, Patel KJ, Nilsen-Hamilton M, Heck DE, Laskin JD, Laskin DL. (2007) Acute endotoxemia is associated with upregulation of lipocalin 24p3/Lcn2 in lung and liver. Exp Mol Pathol. 83(2):177-87.

Weinberger B, Vetrano AM, Syed K, Murthy S, Hanna N, Laskin JD, Laskin DL. (2007) Influence of labor on neonatal neutrophil apoptosis, and inflammatory activity. Pediatr Res. 61(5 Pt 1):572-7.

Gray JP, Heck DE, Mishin V, Smith PJ, Hong JY, Thiruchelvam M, Cory-Slechta DA, Laskin DL, Laskin JD. (2007) Paraquat increases cyanide-insensitive respiration in murine lung epithelial cells by activating an NAD(P)H:paraquat oxidoreductase: identification of the enzyme as thioredoxin reductase. J Biol Chem. 282(11):7939-49.

Dambach DM. Durham SK. Laskin JD. Laskin DL. (2006) Distinct roles of NF-kappaB p50 in the regulation of acetaminophen-induced inflammatory mediator production and hepatotoxicity. Toxicol Appl Pharmacol. 211(2):157-65.

Martey CA. Vetrano AM. Whittemore MS. Mariano TM. Heck DE. Laskin DL. Heindel ND. Laskin JD. (2005) Inhibition of interferon-gamma signaling by a mercurio-substituted dihydropsoralen in murine keratinocytes. Biochem Pharmacol. 70(12):1726-34.

Vetrano AM. Heck DE. Mariano TM. Mishin V. Laskin DL. Laskin JD. (2005) Characterization of the oxidase activity in mammalian catalase. J Biol Chem. 280(42):35372-81.

Weinberger B. Hanna N. Laskin JD. Heck DE. Gardner CR. Gerecke DR. Laskin DL. (2005) Mechanisms mediating the biologic activity of synthetic proline. glycine. and hydroxyproline polypeptides in human neutrophils. Mediators Inflamm. (1):31-8.

Heck DE. Kagan VE. Shvedova AA. Laskin JD. (2005) An epigrammatic (abridged) recounting of the myriad tales of astonishing deeds and dire consequences pertaining to nitric oxide and reactive oxygen species in mitochondria with an ancillary missive concerning the origins of apoptosis. Toxicology. 208(2):259-71.

Hanna N. Vasquez P. Pham P. Heck DE. Laskin JD. Laskin DL. Weinberger B. (2005) Mechanisms underlying reduced apoptosis in neonatal neutrophils. Pediatr Res. 57(1):56-62.

Fakhrzadeh L. Laskin JD. Laskin DL. (2004) Ozone-induced production of nitric oxide and TNF-alpha and tissue injury are dependent on NF-kappaB p50. Am J Physiol Lung Cell Mol Physiol. 287(2):L279-85.

Heck DE. Gerecke DR. Vetrano AM. Laskin JD. (2004) Solar ultraviolet radiation as a trigger of cell signal transduction. Toxicol Appl Pharmacol. 195(3):288-97.

Chiu H. Gardner CR. Dambach DM. Durham SK. Brittingham JA. Laskin JD. Laskin DL. (2003) Role of tumor necrosis factor receptor 1 (p55) in hepatocyte proliferation during acetaminophen-induced toxicity in mice. Toxicol Appl Pharmacol. 193(2):218-27.

Gardner CR. Laskin JD. Dambach DM. Chiu H. Durham SK. Zhou P. Bruno M. Gerecke DR. Gordon MK. Laskin DL. (2003) Exaggerated hepatotoxicity of acetaminophen in mice lacking tumor necrosis factor receptor-1. Potential role of inflammatory mediators. Toxicol Appl Pharmacol. 192(2):119-30.

Fakhrzadeh L. Laskin JD. Gardner CR. Laskin DL. (2004) Superoxide dismutase-overexpressing mice are resistant to ozone-induced tissue injury and increases in nitric oxide and tumor necrosis factor-alpha. Am J Respir Cell Mol Biol. 30(3):280-7.

Chiu H. Gardner CR. Dambach DM. Brittingham JA. Durham SK. Laskin JD. Laskin DL. (2003) Role of p55 tumor necrosis factor receptor 1 in acetaminophen-induced antioxidant defense. Am J Physiol Gastrointest Liver Physiol. 285(5):G959-66.

Sur R. Heck DE. Mariano TM. Jin Y. Murphy WJ. Laskin JD. (2002). UVB light suppresses nitric oxide production by murine keratinocytes and macrophages. Biochem Pharmacol. 64:1469-1481.

Gardner CR. Laskin JD. Dambach DM. Sacco M. Durham SK. Bruno MK. Cohen SD,Gordon MK. Gerecke DR. Zhou P. Laskin DL. (2002). Reduced hepatotoxicity of acetaminophen in mice lacking inducible nitric oxide synthase: potential role of tumor necrosis factor-alpha and interleukin-10. Toxicol Appl Pharmacol. 184:27-36.

Xu X. Mariano TM. Laskin JD. Weisel CP. (2002). Percutaneous absorption of trihalomethanes. haloacetic acids. and haloketones. Toxicol Appl Pharmacol. 184:19-26.

Laskin JD. Heck DE. Laskin DL. (2002). The ribotoxic stress response as a potential mechanism for MAP kinase activation in xenobiotic toxicity. Toxicol Sci. 69:289-291.

Billack B. Heck DE. Mariano TM. Gardner CR. Sur R. Laskin DL. Laskin JD. (2002). Induction of cyclooxygenase-2 by heat shock protein 60 in macrophages and endothelial cells.Am J Physiol Cell Physiol. 283:C1267-1277.

Sunil VR. Connor AJ. Zhou P. Gordon MK. Laskin JD. Laskin DL. (2002). Activation of adherent vascular neutrophils in the lung during acute endotoxemia. Respir Res. 3:21-26.

Laskin DL. Fakhrzadeh L. Heck DE. Gerecke D. Laskin JD. (2002). Upregulation of phosphoinositide 3-kinase and protein kinase B in alveolar macrophages following ozone inhalation. role of NF-kB and STAT-1 in ozone-induced nitric oxide production and toxicity. Mol Cell Biochem. 234-235:91-98.

Martey CA. Vetrano AM. Whittemore MS. Mariano TM. Gentile SL. Heck DE. Laskin DL. Heindel ND. Laskin JD. (2002). Mechanisms of growth inhibition in keratinocytes by mercurio-substituted 4',5'-dihydropsoralens. Biochem Pharmacol. 63:2001-2009.

Ahmad N. Chen LC. Gordon MA. Laskin JD. Laskin DL. (2002). Regulation of cyclooxygenase-2 by nitric oxide in activated hepatic macrophages during acute endotoxemia. J Leukoc Biol. 71:1005-1011.

Weinberger B. Laskin DL. Heck DE. Laskin JD. (2002). Oxygen toxicity in premature infants. Toxicol Appl Pharmacol. 181:60-67.

Fakhrzadeh L. Laskin JD. Laskin DL. (2002). Deficiency in inducible nitric oxide synthase protects mice from ozone-induced lung inflammation and tissue injury. Am J Respir Cell Mol Biol. 26:413-419.

Sunil VR. Connor AJ. Guo Y. Laskin JD. Laskin DL. (2002). Activation of type II alveolar epithelial cells during acute endotoxemia. Am J Physiol Lung Cell Mol Physiol. 282:L872-880.

Sunil VR. Connor AJ. Lavnikova N. Gardner CR. Laskin JD. Laskin DL. (2002). Acute endotoxemia prolongs the survival of rat lung neutrophils in response to 12-O-tetradecanoyl-phorbol 13-acetate. J Cell Physiol. 190:382-389.

Mariano TM. Vetrano AM. Gentile SL. Heck DE. Whittemore MS. Guillon CD. Jabin I. Rapp RD. Heindel ND. Laskin JD. (2002). Cell-impermeant pyridinium derivatives of psoralens as inhibitors of keratinocyte growth. Biochem Pharmacol. 63:31-39.