Department of Chemistry and Biochemistry @ Boise State University

Ken Cornell
Associate Professor of Biochemistry
kencornell@boisestate.edu
SCNC-320
(208)-426-5429

Educational Background

Portland VA Medical Center, Post-doctoral, Biochemistry/ Immunology 1997-1998
Oregon Health & Sciences University, Ph.D. Biochemistry, 1997
Wichita State University, M.S. Microbiology, 1985
Oregon State University, B.S. Microbiology, 1983

Research

An array of research projects are available for students to work on in my lab, including:

1. Antibiotic development targeting bacterial and parasite methionine salvage.
2. Farnesol metabolism in eukaryotic cells
3. Development of forensic reagentsOne of the primary investigations in my lab is the identification of new targets for antimicrobial drug development. One area of focus is “quorum sensing”, a process in which bacteria secrete small molecules that accumulate and signal population wide changes in gene expression. Quorum sensing has been shown to govern coordinated production of such things as biofilms and virulence factors by bacterial populations. We have cloned and expressed the genes for several steps in a microbial methionine salvage pathway that leads to the synthesis of a quorum sensing molecule termed autoinducer II (AI-2). Students are currently working on projects to characterize the substrate specificity, kinetic parameters, and expression profiles for these enzymes. In addition, a number of compounds are being tested as specific enzyme inhibitors and for the ability to block quorum sensing dependent events like biofilm production and colonization in bacterial cultures.

Fellowships / Grants / Awards

Recent grant support includes:

1. “DNA Safeguard” (Co-investigator) Dept. of Defense Appropriations grant 11/01/06 – 10/31/07
2.“Development of Non-polar Electrical Field Flow Fractionation for Membrane Protein Purification” (Principle investigator) Boise State University Faculty Research Grant 07/15/06 – 07/14/07
3. “A Preparative Scale Ultracentrifuge for the College of Arts and Sciences” (Principle Investigator). NSF EPSCoR Research Infrastructure Grant/ Boise State University 09/01/06
4.“Development of Novel Antimicrobial Catheters” (Principle Investigator) NIH R43AI061894. 11/01/05 – 4/30/06
5.“Methylthioribose kinase inhibitors as herbicides and anti-senescence agents in plants” (Principle Investigator). USDA (02-0047) 12/02-6/03

Recent student support for work in my lab:

1. Mountain States Tumor Institute (Jacob Jones, 2005)
2. Merck Foundation (Comfort Hines, 2004-2005; Lee Rooney, 2005; Jeremiah Hull, 2006; Maria Martinez, 2006)
3. INBRE Summer fellowships (Chelsea Isom, 2005, 2006; Andre Rudyi, 2006; Christy Mackenzie, 2005; Brad Hansen, 2006).

Selected Publications and Presentations

1. Hefeneider, SH, Bennett, RM, Pham, TQ, Cornell, KA, McCoy, SH, and Heinrich, MC. (1990) Identification of a cell surface DNA receptor association with systemic lupus erythematosus. J. Invest. Derm. 94(6):79s-84s.

2. Bennett, RM, Cornell, KA, Merritt, MJ, Bakke, AC, Hsu, PH, and Hefeneider, SH. (1991) Autoimmunity to a 28-30 kD cell membrane DNA binding protein: occurrence in selected sera from patients with SLE and Mixed Connective Tissue Disease (MCTD). Clin. Exp. Immunol. 86(3): 374-379.

3. Bennett, RM, Cornell, KA, Merritt, MJ, Bakke, AC, Mourich, D, and Hefeneider, SH. (1992) Idiotypic mimicry of a cell surface DNA receptor: evidence for anti-DNA antibodies being a subset of anti-anti-DNA receptor antibodies. Clin. Exp. Immunol. 90: 428-433.

4. Hefeneider, SH, Cornell, KA, Brown, LE, Bakke, AC, McCoy, SH and Bennett, RM. (1992) Nucleosomes and DNA bind to the same cell-surface molecules and induce cytokine production by murine spleen cells. Clin. Immunol. Immunopath. 63(3): 245-251.

5. Winter, RW, Cornell, KA, Johnson, LL, and Riscoe, MK. (1993) Synthesis and testing of substituted phenylthioribose analogs against Klebsiella pneumoniae. Bioorg. & Med. Chem. Letters 3(10): 2079-2082.

6. Hefeneider, SH, Brown, LE, McCoy, SH, Bakke, AC, Cornell, KA, and Bennett, RM. (1993) Immunization of BALB/c mice with monoclonal anti-DNA antibody induces an anti-idiotypic antibody reactive with a cell-surface DNA binding protein. Autoimmunity 15: 187-194.

7. Winter, RW, Cornell, KA, Johnson, LL, Isabelle, LM, Hinrichs, DJ, and Riscoe, MK. (1995) Hydroxy-anthraquinones as antimalarial agents. Bioorg. & Med. Chem. Letters 5(17): 1927-1932.

8. Winter, RW, Cornell, KA, Johnson, LL, Ignatushchenko, M, Hinrichs, DJ, and Riscoe, MK. (1996) Potentiation of the antimalarial agent Rufigallol. Antimicrobial Agents & Chemo. 40(6): 1408-1411.

9. Cornell, KA, Winter, RW, Tower, PA, and Riscoe, MK. (1996) Affinity purification of 5-methylthioribose kinase and 5’-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Klebsiella pneumoniae.Biochem J. 317: 285-290.

10. Cornell, KA, Swarts, WE, Barry, RA, and Riscoe, MK. (1996) Characterization of recombinant Escherichia coli 5-methylthioadenosine/S-adenosylhomocysteine nucleosidase: analysis of enzymatic activity and substrate specificity. Biochem. Biophys. Res. Commun. 228: 724-732.

11. Winter, RW, Ignatushchenko, M, Ogundahunsi, OAT, Cornell, KA, Oduola, AD, Hinrichs, DJ, and Riscoe, MK. (1997) Potentiation of an antimalarial oxidant drug. Antimicro. Agents &Chemo. 41(7): 1449-1454.

12. Cornell, KA, and Riscoe, MK (1998) Cloning and expression of Escherichia coli 5’-methylthioadenosine /S-adenosylhomocysteine nucleosidase: identification of the pfs gene product. Biochem. Biophys. Acta, 1396: 8-14.

13. Cornell, KA, Bouwer, HGA, Hinrichs, DJ, and Barry, RA (1999) Genetic immunization of mice against Listeria monocytogenes using plasmid DNA encoding listeriolysin O. J. Immunol., 163: 322-329.

14. Brown, JR, Cornell, KA, and Cook, PW (2000) Adenosine- and Adenine-nucleotide-mediated inhibition of normal and transformed keratinocyte proliferation is dependent upon dipyridamole-sensitive adenosine transport. J. Invest. Derm., 115(5) 849-859.

15. Lee, JE, Cornell, KA, Riscoe, MK, and Howell, PL (2001) The crystal structure of E. coli 5’-methylthioadenosine/S-adenosylhomocysteine nucleosidase reveals structural similarity to the purine mucleoside phosphorylases. Structure 9: 941-953.

16. Lee, JE, Cornell, KA, Riscoe, MK, and Howell, PL (2001) Expression, purification, crystallization and preliminary X-ray analysis of E. coli 5’-methylthioadenosine/S-adenosylhomocysteine nucleosidase. Acta crystallographica (D57) 150-152.

17. Winzer, K, Hardie, KR, Burgess, B, Doherty, N, Kirke, D, Holden, MTG, Linforth, R, Cornell, KA, Taylor, AJ, Hill, PJ, Williams, P (2002) LuxS: its role in central metabolism and the in vitro synthesis of 4-hydroxy-5-methyl-3(2H)-furanone. Microbiology 148: 909-922.

18. Lee, JE, Cornell, KA, Riscoe, MK, and Howell, PL (2003) Structure of E. coli 5’-methylthioadenosine/S-adenosylhomocysteine nucleosidase inhibitor complexes provide insight into conformational changes required for substrate binding and catalysis. J. Biol. Chem. 278: 8761-8770

19. Hinrichs, DJ, Cornell, KA, Bouwer, HGA, and Barry, RA (2003) Protective immunization of interferon g knockout mice following intramuscular DNA vaccination. Vaccine 21(17-18): 2131-2141

20. Simon, BE, Cornell, KA, Clark, TR, Chou, S, Rosen, HR, and Barry, RA (2003) DNA vaccination protects mice against challenge with Listeria monocytogenes expressing the hepatitis C virus NS3 protein. Infect. Immun. 71(11): 6372-80.

21. Zhao, G, Wan, W, Mansouri, S, Alfaro, JF, Bassler, BL, Cornell, KA, and Zhou, ZS (2003) Chemical synthesis of S-ribosyl-L-homocysteine and activity assay as a LuxS substrate. Biorg. and Med. Chem. Letts. 13(22): 3897-900.

22. Ku, SY, Yip, P, Cornell, KA, Riscoe, MK, Howell, PL (2004) Crystallization and preliminary X-ray analysis of 5-methylthioribose kinase from Bacillus subtilis and Arabidopsis thaliana. Acta crystallogr.D. Biol Crystallogr. 60(Pt 1):116-9.

23.Lee, JE, Settembre, EC, Cornell, KA, Riscoe, MK, Sufrin, JR, Ealick, SE, Howell, PL (2004) Structural comparison of MTA phosphorylase and MTA/SAH nucleosidase explains substrate preferences and identifies regions exploitable for inhibitor design. Biochemistry. 43: 5159-5169.

24. Cook, PW, Brown, JR, Cornell, KA, Pittelkow, MR (2004) Suprabasal expression of human amphiregulin in the epidermis of transgenic mice induces a severe, early-onset, psoriasis-like skin pathology: expression of amphiregulin in the basal epidermis is also associated with synovitis. Exp Dermatol. 13(6):347-56.

25. Sauter, M, Sára Beszteri, S, Cornell, KA, Rzewuski, G (2004) Functional analysis of methylthioribose kinase genes in plants. Plant Phys. 136: 4061-4071.

26. Lee JE, Singh V, Evans GB, Tyler PC, Furneaux RH, Cornell KA, Riscoe MK, Schramm VL, Howell PL (2005) Structural rationale for the affinity of PICO-and femtomolar transition state analogues of E. coli 5'-methylthioadenosine/s-adenosylhomocysteine nucleosidase. J. Biol Chem. 280(18):18274-82.

27. Lee JE, Smith GD, Horvatin C, Huang DJ, Cornell KA, Riscoe MK, Howell PL (2005) Structural snapshots of MTA/AdoHcy nucleosidase along the reaction coordinate provide insights into enzyme and nucleoside flexibility during catalysis. J. Mol. Biol. 352(3): 559-574.

28. Lee JE, Luong W, Huang DJ, Cornell KA, Riscoe MK (2005) Mutational analysis of a nucleosidase involved in quorum-sensing autoinducer-2 biosynthesis. Biochemistry 44(33): 11049-11057.

29. Parveen N, Cornell KA, Bono JL, Chamberland C, Rosa P, Leong JM (2006) Bgp, a secreted GAG-binding protein of B. burgdorferi strain N40, displays nucleosidase activity and is not essential for infection of immunodeficient mice. Infect. Immun. 74(5):3016-20.