The specific area of Dr. Sharma's research is toxicology. Current research in his laboratory deals with the molecular and biochemical mechanisms of toxic responses of environmental chemicals in biological systems, particularly those involving the immune system and the nervous system. A major project deals with the mechanism of action of fumonisin, a common mycotoxin and contaminant in corn and other cereals, in cellular signaling pathways involving cytokines.

The overall objective of this research is to define why fumonisin has selective effects in different tissues and different species of animals. Another project involves the modulation of gene expression by retinoic acid (vitamin A metabolite) in developing organisms. Effects of retinoic acid in modulating the expression of oncogenes and how it relates to differentiation and apoptosis of embryonic stem cells is being investigated.

He, Q., Kim, J-Y, and Sharma, R. P. (2005). Fumonisin B₁ hepatotoxicity in mice is attenuated by depletion of Kupffer cells by gadolinium chloride. Toxicology, 207: 137-147.

Johnson, V. J., Kim, S.-H., and Sharma R. P. (2005). Aluminum-maltolate induces apoptosis and necrosis in neuro-2a cells: potential role for p53 signaling. Toxicol. Sci., 83:329-339.

Osuchowski, M. F., Edwards, G. L., and Sharma, R. P. (2005). Fumonisin B₁-induced neurodegeneration in mice after intracerebroventricular infusion is concurrent with disruption of sphingolipid metabolism and activation of proinflammatory signaling. NeuroToxicology, 26:211-221.

Kim S.-H., and Sharma R. P. (2005). Mercury alters endotoxin-induced inflammatory cytokine expression in liver: differential roles of p38 and extracellular signal-regulated mitogen-activated protein kinases. Immunopharmacol. Immunotoxicol., 27: 123-135.

He, Q., Riley, R. T., and Sharma R. P. (2005). Myriocin prevents fumonisin B₁-induced sphingoid base accumulation in mice liver without ameliorating hepatotoxicity. Food Chem. Toxicol., 43: 969-979.

Osuchowski, M. F., He, Q. and Sharma, R. P. (2005). Endotoxin exposure alters brain and liver effects of fumonisin B₁ in Balb/c mice: Implication of blood brain barrier, Food Chem. Toxicol., 43:1389-1397.

He, Q., and Sharma, R. P. (2005). Inhibition of tumor necrosis factor a signaling by anti-tumor necrosis factor a antibodies and pentoxifylline is unable to prevent fumonisin hepatotoxicity in mice. Toxicon, 46: 404-413.

Osuchowski, M. F., and Sharma R. P. (2005). Fumonisin B₁ induces necrotic cell death in BV2 cells and murine cultured astrocytes and is antiproliferative in BV2 cells while N2A cells and primary cortical neurons are resistant. NeuroToxicology, 26: 981-992.

Sharma, R. P., He,Q., and Riley, R. T. (2005). Lupus-prone NZBWF1/J mice, defective in cytokine signaling, are resistant to fumonisin hepatotoxicity despite accumulation of liver sphinganine. Toxicology, 216:59-71.

Kim, J-Y., Kim, S-H., Johnson, V. J. and Sharma R. P. (2005). Extracellular signal-regulated kinase (ERK)-signaling-dependent G2/M arrest and cell death in murine macrophages by cadmium.. Environ. Toxicol. Chem., in press.

Kim, Jiyoung and Sharma, R. P. (2005). Cadmium-induced apoptosis in murine macrophages is antagonized by antioxidants and caspase inhibitors. J. Toxicol. Environ. Health, in press.

Sharma, N., Suzuki, H., He, Q, and Sharma, R. P. (2005). Tumor necrosis factor a-mediated activation of c-Jun NH2-terminal kinase as a mechanism for fumonisin B₁-induced apoptosis in murine primary hepatocytes. J. Biochem. Molec. Toxicol., in press.

Kim, S-H., Johnson, V. J., Shin, T-Y., and Sharma, R. P. (2004). Selenium attenuates lipopolysaccharide-induced oxidative stress responses through modulation of p38 MAPK and NF-ĸB signaling pathways. Exp. Biol. Med., 229:203-213.

Osuchowski, M. F., Johnson, V. J., He, Q., and Sharma, R. P. (2004). Myriocin, a serine palmitoyltransferase inhibitor, alters regional brain neurotransmitter levels without concurrent inhibition of the brain sphingolipid biosynthesis in mice. Toxicol. Lett., 147:87-94.

Kim, S-H. Kim, J, and Sharma, R. P. (2004). Inhibition of p38 and ERK MAP kinases blocks endotoxin-induced nitric oxide production and differentially modulates cytokine expression. Pharmacol. Res., 49:433-439.

Kim, S-H., and Sharma, R. P. (2004). Mercury-induced apoptosis and necrosis in murine macrophages: Role of calcium-induced reactive oxygen species and p38 mitogen-activated protein kinase signaling. Toxicol. Appl. Pharmacol., 196:47-57.

Gopee, N. V., Johnson, V. J. and Sharma, R. P. (2004). Sodium selenite-induced apoptosis in murine B-lymphoma cells is associated with inhibition of protein kinase C-d, nuclear factor ĸB and inhibitor of apoptosis protein. Toxicol. Sci., 78:204-214.

He, Q., Johnson, V. J., Osuchowski, M. F., and Sharma, R. P. (2004). Inhibition of serine palmitoyltransferase by myriocin, a natural mycotoxin, causes induction of c-myc in mouse liver. Mycopathologia. 157:339-347.

He, Q., Kim, J-Y., and Sharma R. P. (2004). Silymarin protects against liver damage in BALB/c mice exposed to fumonisin B₁ despite increasing accumulation of free sphingoid bases, Toxicol. Sci., 80:335-342.

Johnson, V. J., He, Q., Osuchowski, M. F. and Sharma, R. P. (2004). Disruption of sphingolipid homeostasis by myriocin, a mycotoxin, reduces thymic and splenic T-lymphocyte populations. Toxicology, 201:67-75.

Gopee, N. V., and Sharma, R. P. (2004). The mycotoxin fumonisin B₁ transiently activates nuclear factor-ĸB, tumor necrosis factor a and caspase 3 via protein kinase C¥-dependent pathway in porcine renal epithelial cells. Cell Biol. Toxicol., 20:197-212.

Sharma, N., He. Q., and Sharma, R. P. (2004). Augmented fumonisin B₁ toxicity in co-cultures: evidence for crosstalk between macrophages and nonparenchymatous liver epithelial cells involving proinflammatory cytokines. Toxicology, 203: 239-251.

Kim, J-Y., and Sharma, R. P. (2004). Calcium-mediated activation of c-jun NH2-terminal kinase (JNK) and apoptosis in response to cadmium in murine macrophages. Toxicol. Sci., 81: 518-527.

Sharma, N., He. Q., and Sharma, R. P. (2004). Sphingosine kinase activity confers resistance to apoptosis by fumonisin B₁ in human embryonic kidney (HEK-293) cells. Chem-Biol. Interactions, 151:33-42.

Sharma, R. P., McGraw R., and Dugyala, R. R. (2003). "Cloning and characterization of hamster fetal retinoic acid receptor isoforms." J. Exp. Anim. Sci., 43:125-134.

Johnson, V. J., He, Q., Osuchowski, M. F., and Sharma, R. P. (2003). "Physiological responses to a natural antioxidant flavanoid mixture, silymarin, in BALB/c mice: III. Silymarin inhibits T lymphocyte function at low doses but stimulates inflammatory process at high doses." Planta Medica, 69: 44-49.

Johnson, V. J. and Sharma, R. P. (2003). "Aluminum disrupts the proinflammatory cytokine/neurotrophin balance in primary brain rotation-mediated aggregate cultures: possible role in neurodegeneration." NeuroToxicology, 24:261-268.

Sharma, R. P., He, Q., and Johnson, V. J. (2003). "Deletion of interferon g reduces fumonisin-induced hepatotoxicity in mice via alterations in inflammatory cytokines and apoptotic factors." J. Interferon Cytokine Res., 23:13-23.

Sarkar, S. A., and Sharma, R. P. (2003). "Modulation of p53 after maternal exposure to all-trans-retinoic acid in Swiss Webster mouse fetuses." Exp. Mol. Pathol., 74: 298-308.

Johnson, V. J., He, Q., Kim, S. H., Kanti, A., and Sharma, R. P. (2003). "Increased susceptibility of renal epithelial cells to TNFa-induced apoptosis following treatment with fumonisin B1." Chem.-Biol. Interact., 145:297-309.

Gopee, N. V., and Sharma, R. P. (2003). "Sphingoid bases and their phosphates: Transient activation and delayed repression of protein kinase C isoforms and their possible involvement in fumonisin B1 cytotoxicity." Toxicology, 187:239-250.

Kim, S. H. and Sharma, R. P. (2003). "Cytotoxicity of inorganic mercury in murine T and B lymphoma cell lines: involvement of reactive oxygen species, Ca2+ homeostasis, and cytokine gene expression." Toxicol. In Vitro, 17:385-395.

Kim, S.-H, Johnson, V. J., and Sharma, R. P. "Oral exposure to inorganic mercury alters T-lymphocyte phenotypes and cytokine expression in BALB/c mice." Arch. Toxicol. In press.

Gopee, N. V., He, Q., and Sharma, R. P. "Fumonisin B1-induced apoptosis is associated with delayed inhibition of protein kinase C, nuclear factor-kB and tumor necrosis factor a in LLC-PK1 cells." Chem-Biol. Interact., 146:31-46.

Sharma, R. P., He, Q., Johnson, V. J., and Voss, K. A. (2003). "Increased expression of CD95 ligand and other apoptotic signaling factors by fumonisin B1, a hepatotoxic mycotoxin, in livers of mice lacking tumor necrosis factor a." Cytokine, 24:226-236.

Bhandari, N. and Sharma, R. P. (2002). "Fumonisin B1-induced alterations in cytokine expression and apoptosis signaling genes in mouse liver and kidney after an acute exposure." Toxicology, 172:81-92.

Bhandari, N., and Sharma, R. P. (2002). "Modulation of selected cell signaling genes in mouse liver by fumonisin B1." Chem-Biol. Interact., 139:317-331.

Bhandari, N., Enongene, E., Riley, R. T., Meredith, F. I., and Sharma, R. P. (2002). "Temporal expression of fumonisin B1-induced tumor necrosis factor alpha and interferon gamma in mice." Comp. Biochem. Physiol:C. 131:113-122.

Sarkar, S. A. and Sharma, R. P. (2002). "Modulation of c-myc, Max, and Mad gene expression during neural differentiation of embryonic stem cells by all-trans-retinoic acid." Gene Expression, 10:125-135.

He, Q., Riley, R. T. and Sharma, R. P. (2002). "Pharmacological antagonism of fumonisin B1 cytotoxicity in porcine renal epithelial cells (LLC-PK1): A model for reducing fumonisin-induced nephrotoxicity in vivo." Pharmacol. Toxicol., 90:268-277.

Bhandari, N., Brown, C. C., and Sharma (2002). "Fumonisin B1-induced localized activation of cytokine network in mouse liver." Food Chem. Toxicol. 40:23-31.

Voss, K. A., Howard, P. C., Riley, R. T., Sharma, R. P., Bucci, T. J., and Lorentzen, R. J. (2002). "Carcinogenicity and mechanism of action of fumonisin B1, a mycotoxin produced by Fusarium moniliforme (=F. verticillioides)." Cancer Detect. Prevent., 26:1-9, 2002.

Sarkar, S. A., and Sharma, R. P. (2002). "All-trans-retinoic acid-mediated modulation of p53 during neural differentiation in murine embryonic stem cells." Cell Biol. Toxicol., 18:243-257.

Enongene, E. N., Sharma, R. P., Bhandari, N., Miller, J. D., Meredith, F. I., Voss, K. A., and Riley, R. T. (2002). "Persistence and reversibility of the elevation in free sphingoid bases induced by fumonisin inhibition of ceramide synthase." Toxicol. Sci., 67:173-181.

He, Q., Osuchowski, M. F., Johnson, V. J., and Sharma, R. P. (2002). "Biological responses of a natural antioxidant flavonoid, silymarin, in BALB/c mice. I. Induction of transforming growth factor b1 and c-myc in liver with marginal effects on other genes." Planta Medica, 68:672-675.

Kim, S-H., Johnson, V. J., and Sharma, R. P. (2002). "Mercury inhibits nitric oxide production but activates pro-inflammatory cytokine expression in murine macrophage: Differential modulation of NFkB and p38 MAPK signaling pathways." Nitric Oxide, 7:67-74.

Sarkar, S. A., and Sharma, R. P. (2002). "Expression of selected apoptosis related genes, MIF, IGIF, and TNFa, during retinoic acid-induced neural differentiation in murine embryonic stem cells." Cell Struct. Funct., 27:99-107.

Sarkar, S. A., and Sharma, R. P. (2002). "Expression of c-Myc and other apoptosis-related genes in Swiss Webster mouse fetuses after maternal exposure to all-trans-retinoic acid." Reproductive Toxicology, 16:245-252.

He, Q., Bhandari, N., and Sharma, R. P. (2002). "Fumonisin B1 alters sphingolipid metabolism and tumor necrosis factor a expression in heart and lung of mice." Life Sci., 71:2015-2023.

Sharma, R. P., He, Q., Meredith, F. I., Riley, R. T., and Voss, K. A. (2002). "Paradoxical role of tumor necrosis factor a in fumonisin-induced hepatotoxicity in mice." Toxicology, 180:221-232.

Johnson, V. J., Osuchowski, M. F., He, Q., and Sharma, R. P. (2002). "Physiological responses to a natural antioxidant flavanoid mixture, silymarin, in BALB/c mice: II. Alterations in thymic differentiation correlates with changes in c-myc gene expression." Planta Medica, 68:961-965.