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Kansas State University

Faculty

 

 

Kristopher Silver

PhD, Environmental Toxicology, Cornell University, 2005
Postdoctoral, Michigan State University, 2005-2006
Postdoctoral, Kansas State University, 2006-2011
Postdoctoral, USDA-ARS-CGAHR-SPIRU, 2011-2013

Research Assistant Professor
Coles Hall 138
Phone: (785) 532-4864 
Email: ksilver@vet.k-state.edu

 

 

 


 

Research Interests:

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the alleviation of pain and inflammation, but their use is associated with a suite of negative side-effects, particularly in the gastrointestinal (GI) tract. As many as 50% of people taking NSAIDs daily show some symptoms of GI toxicity and 4% develop 4% of individuals develop serious problems requiring medical intervention. The mechanisms underlying GI toxicity caused by NSAIDs initially were thought to arise out of indiscriminate inhibition of prostaglandin synthesis; however, mounting evidence suggests that more diverse mechanisms are involved. Understanding how NSAID-induced toxicity occurs will allow the development of intervention strategies to alleviate symptoms and/or guide future efforts to synthesize new categories of NSAIDs that do not promote GI damage.

Our research program focuses on understanding the molecular mechanisms underlying NSAID-induced GI damage. Our primary focus is identifying the mechanism(s) through which NSAIDs disrupt intestinal restitution, the cell migration-dependent process by which defects in the intestinal epithelia are repaired. We have demonstrated that NSAID-induced loss of calpain protease expression and activity results in significant reductions in cell migration in vitro and in vivo. We have also begun to evaluate the effects of NSAIDs on gene expression in intestinal epithelia both in the rat and horse. In addition, we are uing next generation sequencing techniques to examine the effects of NSAIDs on microbial populations of the equine GI tract.

 

Selected Publications

von Stein, F, KS Silver, DM Soderlund. 2013. Indoxacarb, Metaflumizone, and Other Sodium Channel Inhibitor Insecticides: Mechanism and Site of Action on Mammalian Voltage-Gated Sodium Channels. Pesticide Biochemistry and Physiology 106: 101-112.

Goodman CL, D Stanley, JA Ringbauer Jr, RW Beeman, KS Silver, Y Park. 2012. A cell line derived from the red flour beetle Tribolium castaneum (Coleoptera: Tenebrionidae). In Vitro Cellular & Developmental BiologyAnimal 48: 426-433.

Silver, KS, A Desourmaux, LC Freeman, and JD Lillich. 2012. Expression of pleiotrophin, an important regulator of cell migration, is inhibited in intestinal epithelial cells by treatment with non-steroidal anti-inflammatory drugs.  Growth Factors 30: 258-266.

Lillich, JD, W Ray-Miller, KS Silver, E Davis, and BD Schultz. 2011.  Intra-abdominal hyaluronan concentration in peritoneal fluid of horses with sudden signs of severe abdominal pain.  American Journal of Veterinary Research.  72:  1666-1673.

Song, W, KS Silver*, Y Du, Z Liu, K Dong.  2011.  Analysis of the action of lidocaine on insect sodium channels.  Insect Biochemistry and Molecular Biology 41:  36-41.

Silver, KS, L Leloup, LC Freeman, A Wells, JD Lillich.  2010.  Non-steroidal anti-inflammatory drugs inhibit calpain activity and membrane localization of calpain 2 protease.  International Journal of Biochemistry and Cell Biology 42:  2030-2036.

Silver, KS, W Song, Y Nomura, V Salgado, K Dong.  2010. Mechanism of action of sodium channel blocker insecticides (SCBIs) on insect sodium channels.  Pesticide Biochemistry and Physiology 97:  87-92.

Silver, KS, W Song, Y Nomura, V Salgado, K Dong. 2009. Role of the sixth segment of domain IV of the cockroach sodium channel in the action of sodium channel-blocker insecticides.  Neurotoxicology 30:  613-621.

Raveendran, NN, KS Silver*, LC Freeman, D Narvaez, K Weng, S Ganta, JD Lillich.  2008.  Drug Induced Alterations to Gene and Protein Expression in IEC-6 Cells Suggest a Role for Calpains in the Gastrointestinal Toxicity of Nonsteroidal Anti-inflammatory Agents.  Journal of Pharmacology and Experimental Therapeutics 325:  389-399.

Freeman, LC, DF Narvaez, A McCoy, FB von Stein, S Young, KS Silver, S Ganta, D Koch, R Hunter, RF Gilmour, JD Lillich.  2007.  Depolarization and Decreased Surface Expression of K+ Channels Contribute to NSAID-Inhibition of Intestinal Restitution.  Biochemical Pharmacology 74:  74-85.