Dr. Bruce Geller, Professor

geller2 Office 434 Nash Hall
Phone 541-737-1845
FAX 541-737-0496
Email gellerb@oregonstate.edu
Education Ph.D. University of Utah

Research:  Antisense antibiotics

Courses Taught:   MB 310, Bacterial Molecular Genetics; MB 312, Bacterial Physiology and Metabolism; MB 456/556, Microbial Genetics and Biotechnology

Live Press Conference at ASM ICAAC: http://www.microbeworld.org/podcasts/asm-live/asm-live-archives/1764-icaac-2014-new-antimicrobial-strategy-silences-ndm-1-resistance-gene-in-pathogens

RESEARCH

Antisense Antibiotics. In collaboration with Sarepta, Inc. and academic colleagues, we are developing antisense antibiotics for use in life-threatening diseases caused by antibiotic-resistant bacteria such as Acinetobacter baumannii, Burkholderia cepacia, Pseudomonas aeruginosa, and Escherichia coli.  Phosphorodiamidate morpholino oligomers (PMOs) are synthetic DNA mimics that inhibit expression of specific mRNA. PMOs use the same four bases as DNA, but have a modified linker between bases. The modified linker makes the antisense molecule resistant to nucleases, which is required for in vivo therapeutics. To improve entry into bacteria, we have covalently attached membrane-penetrating peptides. Peptide-PMOs (PPMO) targeted to essential genes of various pathogenic bacteria reduce viability by orders of magnitude in pure culture, tissue culture, and in animal models of infection. PPMOs are often more potent than many traditional antibiotics such as ampicillin and tetracycline.

SELECTED PUBLICATIONS

Pub Med

 

Howard, J.J., Sturge, C.R., Moustafa, D.A., Daly, S.M., Marshall-Batty, K.R., Felder, C.F., Zamora, D., Yabe-Gill, M., Labandeira-Rey, M., Bailey, S.M., Wong, M., Goldberg, J.B., Geller, B.L., and Greenberg, D.E.  2017.  Inhibition of Pseudomonas aeruginosa by Peptide-conjugated Phosphorodiamidate Morpholino Oligomers.  Antimicrob. Agents Chemother. Jan 30. pii: AAC.01938-16. doi: 10.1128/AAC.01938-16. [Epub ahead of print] PMID: 28137807

Otsuka, T., Brauer, A.L., Kirkham, C., Sully, E.K., Pettigrew, M.M., Kong, Y., Geller, B.L., and Murphy, T.F.  2017.  Antimicrobial activity of antisense peptide-peptide nucleic acid conjugates against non-typeable Haemophilus influenzae in planktonic and biofilm forms.  J. Antimicrob. Chemother.  72(1):137-144.

Sully, E.K., Geller, B.L., Li, L., Moody, C.M., Bailey, S.M., Moore, A.L., Wong, M., Nordmann, P., Daly, S.M., Sturge, C.R., Greenberg, D.E.  2016.  Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) restores carbapenem susceptibility to NDM-1-positive pathogens in vitro and in vivo.  J.  Antimicrob Chemother. pii: dkw476. doi: 10.1093/jac/dkw476. [Epub ahead of print] PMID: 27999041

Sully, E.K. and Geller, B.L. 2016.  Antisense antimicrobial therapeutics.  Curr. Opin. Microbiol. 33:47-55.

Greenberg, D.E., Sturdevant, D.E., Marshall-Batty, K.R., Chu, J., Pettinato, A.M., Virtaneva, K., Lane, J., Geller, B.L., Porcella, S.F., Gallin, J.I., Holland, S.M., and Zarember, K.A.  2015.  Simultaneous host-pathogen transcriptome analysis during Granulibacter bethesdensis infection of neutrophils from healthy subjects and patients with chronic granulomatous disease.  Infect. Immun.  83(11):4277-92.

Geller, B.L., and Greenberg, D.E.  2014.  Peptide-conjugated Phosphorodiamidate Morpholino Oligomers:  A New Strategy for Tackling Antibiotic Resistance. Ther. Deliv. 5(3): 243-5.

Geller, B.L., Marshall-Batty, K., Schnell, F.J., McKnight, M.M., Iversen, P.L., and Greenberg, D.E.  2013.  Gene-Silencing Antisense Oligomers Inhibit Acinetobacter Growth in vitro and in vivo.  J. Infect. Dis.

Reese, K.A., Lupfer, C., Johnson, R.C.Mitev, G.M., Mullen, V.M., Geller, B.L., and Pastey, M.  2013.  A Novel Lactococcal Vaccine Expressing a Peptide from the M2 Antigen of H5N2 Highly Pathogenic Avian Influenza Virus Prolongs Survival of Vaccinated Chickens.  Vet. Med. Intl. Article 316926.

Puckett, S.E., K.A. Reese, G.M. Mitev, V. Mullen, R.C. Johnson, K.R. Pomraning, B.L. Mellbye, L.D. Tilley, P.L. Iversen, M. Freitag and B.L. Geller.  2012.  Bacterial Resistance to Antisense Peptide-Phosphorodiamidate Morpholino Oligomers.  Antimicrob. Agents Chemother. 56:6147-6153.

Panchal, R.G., B.L. Geller, B. Mellbye, D. Lane, P.L. Iversen and S. Bavari.  2012.  Peptide Conjugated Phosphorodiamidate Morpholino Oligomers Increase Survival of Mice Challenged with Ames Bacillus anthracis.  Nuc. Acid Therap. 22:305-311.

Greenberg, D. E., K. R. Marshall-Batty, L. R. Brinster, K. A. Zarember, P. A. Shaw, B. L. Mellbye, P. L. Iversen, S. M. Holland, and B. L. Geller. 2010. Antisense Phosphorodiamidate Morpholino Oligomers Targeted to an Essential Gene Inhibit Burkholderia cepacia complex.  J. Infect. Dis., 201(12):1822-30.

Mellbye, B. L., D. D. Weller, J. N. Hassinger, M. D. Reeves, C. E. Lovejoy, P. L. Iversen, and B. L. Geller. 2010. Cationic Phosphorodiamidate Morpholino Oligomers Efficiently Prevent Growth of Escherichia coli in vitro and in vivo. J. Antimicrob. Chemother. 65:98-106.

Mitev, G. M., B. L. Mellbye, P. L. Iversen, and B. L. Geller. 2009. Inhibition of Intracellular Growth of Salmonella enterica serovar 1 typhimurium in Tissue. Antimicrob. Agents Chemother. 53:3700-3704.

Shen, N., J. Ko, G. Xiao, D. Wesolowski, G. Shan, B. Geller, M. Izadjoo, and S. Altman. 2009. Inactivation of Expression of Several Genes in a Variety of Bacterial Species by EGS Technology. Proc. Natl. Acad. Sci. U.S.A. 106:8163-8168.

Mellbye, B. L., S. E. Puckett, L. D. Tilley, P. L. Iversen, and B. L. Geller. 2009. Variations in Amino Acid Composition of Antisense Peptide-Phosphorodiamidate Morpholino Oligomer Affect Potency Against Escherichia coli in vitro and in vivo. Antimicrob. Agents Chemother. 53:525-530.

Tilley, L., B. Mellbye, S. E. Puckett, P. L. Iversen, and B. L. Geller. 2007. Antisense Phosphorodiamidate Morpholino Oligomer-Peptide Conjugate: Dose-Response in Mice Infected with Escherichia coli. J. Antimicrob. Chemother.  59:66-73.

Tilley, L., O.S. Hine, J.A. Kellogg, J.N. Hassinger, D. Weller, P.L. Iversen, and B.L. Geller. 2006. Gene-Specific Effects of Antisense Phosphorodiamidate Morpholino Oligomer-Peptide Conjugates on Escherichia coli and Salmonella typhimurium in Pure Culture and in Tissue Culture. Antimicrob, Agents Chemother. 50: 2789-2796.

Geller, B.L., J. Deere, L. Tilley, and P.L. Iversen. 2005. Antisense phosphorodiamidate morpholino oligomer inhibits viability of Escherichia coli in pure culture and in mouse peritonitis. J. Antimicrob. Chemother. 55:983-988.

Deere, J., P. Iversen, and B.L. Geller. 2005 Antisense phosphorodiamidate morpholino oligomer length and target position effect on gene-specific inhibition in Escherichia coli. Antimicrob. Agents Chemother. 49:249-255.

Geller, B.L., J.D. Deere, D.A. Stein, A.D. Kroeker, H.M. Moulton, and P.L. Iversen. 2003. Inhibition of gene expression in Escherichia coli by antisense phosphorodiamidate morpholino oligomers. Antimicrob. Agents Chemother. 47:3233-3239.