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Shivendra Shukla

Shivendra Shukla, Tutor

Margaret Proctor Mulligan Professor, Medical Pharmacology & Physiology
M531 Medical Science Building, Pharmacology
573-882-2740
shuklasd@missouri

Research area(s):

Epigenetic and cell signaling effects of ethanol on liver: The effect of ethanol on cell signaling in liver cells (hepatocytes) is being investigated with the goal to identify the key steps altered by ethanol in (a) MAP kinase pathway and (b) in the nuclear responses. Proteomic analysis of the kinase substrates affected by ethanol is one of the issues being addressed.  In the nuclear effects, the focus is on the chromatin histone modification(s) and the goal is to understand the molecular mechanism and transcriptional consequence of ethanol induced epigenetic histone modifications (i.e. acetylation, methylation and phosphorylation). The CHIP assay, gene and protein array technologies are being utilized to identify the ethanol affected genes and proteins relevant to alcoholic liver disease. The laboratory also uses pharmacological agents in animals/ in vivo for translational implications of these studies.

 Platelets and vascular remodelling: The role of blood platelets and its secretory products in vascular responses is another topic of focus. We have established the pharmacological properties of platelet activating factor (PAF) and its receptor associated cell signaling responses in human and rabbit platelets. Our new observations show that upon activation, human platelets secrete specific PKC isozymes (PKC α, βII and δ). This raises the question of extracellular role of these PKCs on adjacent cells (eg. endothelial or smooth muscle cells) in the vasculature or at the site of injury where platelets adhere and secrete these isozymes. Diabetic platelets, which exhibit hypersensitivity, are being used to test whether secretion of these PKC's have significance in the thromboembolic complications observed in diabetics.

Publications:

Aroor, A. & Shukla, S.D. (2004). MAP Kinase signaling in diverse effects of ethanol. Life Sciences, 74, 2339-2364. PMID: 15027449.

Aroor, A., James, T. T., Jackson, D. E. & Shukla, S. D. (2010). Differential changes in MAP Kinases, histone modifications and liver injury in rats acutely treated with ethanol. Alcoholism: Clinical & Experimental Research, 9, 1543-1551. PMID: 20586759  PMCID: PMC2929313.

Aroor, A., Lee, Y. & Shukla, S. D. (2009).Activation of MEK1/2 and p42/44 MAPK by Angiotensin II in hepatocyte nucleus and their potentiation by ethanol. Alcohol, 43, 315-322. PMID: 19560630 PMCID: PMC2743527.

Kim, J  & Shukla, S.D. (2006). Acute in vivo effect of ethanol (binge drinking) on histone H3 modifications in rat tissues. Alcohol & Alcoholism, 41, 126-132. PMID: 16314425.

Lee, Y. & Shukla, S.D. (2007). Histone H3-Serine -10 & -28 phosphorylation by ethanol and acetaldehyde in hepatocytes is mediated by p38MAPKinase. European Journal of Pharmacology, 573, 29-38. PMID: 17643407 PMCID: PMC2723821.

Lee, Y., & Shukla, S.D. (2005). Pro- & anti- apoptotic role of JNK in ethanol and acetaldehyde exposed hepatocytes. European Journal of Pharmacology, 508, 31-45. PMID: 15680252.

Park, P., Aroor, A. & Shukla, S.D. (2006). Role of Ras in ethanol modulation of Angiotensin II activated p42/44 MAP kinase in rat hepatocytes. Life Sciences, 79, 2357-2363. PMID: 16950409.

Shukla, S.D., Velazquez, J., French, S. W., Lu, S., Ticku, M. K. & Zakhari, S. (2008). Emerging role of epigenetics in the actions of alcohol. Alcoholism: Clinical & Experimental Research, 32, 1525-1534. PMID: 18616668.

Weng, Y., Aroor, A. & Shukla, S.D. (2008). Ethanol inhibition of Angiotensin II stimulated Tyr-705 and Ser-727 STAT3 phosphorylation in cultured rat hepatocytes: Relevance to activation of p42/44 MAP Kinase. Alcohol, 42, 397-406.  PMID: 18411006.

Weng, Y.I. & Shukla, S.D. (2003). Effects of chronic ethanol on the angiotensin II-mediated p42/44 MAP kinase and phosphorylase a activation in rat hepatocytes.  Alcohol, 29, 83-90. PMID: 12782249.

2009 Curators of the University of Missouri. DMCA and other copyright information. An equal opportunity/affirmative action institution.

For more information about the program, e-mail alcoholstudies@missouri.edu.