James McNamara, PhD

Portrait
Associate Professor of Internal Medicine - Hematology, Oncology and Blood and Marrow Transplantation

Contact Information

Lab: 3256 CBRB
Iowa City, IA 52242
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Office: 3270C CBRB
Iowa City, IA 52242
319-335-8491

Education

BS, Chemical Engineering, The University of Virginia, Charlottesville, VA
PhD, Neurobiology, Duke University, Durham, NC

Postdoctoral Fellow, Duke University Medical Center

Education/Training Program Affiliations

Interdisciplinary Graduate Program in Molecular Medicine, Interdisciplinary Graduate Program in Neuroscience

Research Summary


My research is primarily focused on nucleic acid-based diagnostic technologies for infectious diseases. With a simple quenched fluorescent oligonucleotide probe format (see Figure), my research group can rapidly and selectively detect the presence of a variety of bacterial pathogens via the unique properties of their nucleases. By identifying an appropriate oligonucleotide sequence and chemical composition, we tailor each probe to be specifically activated by a target nuclease. Chemically modified nucleotides are used to facilitate resistance to non-target nucleases. For instance, oligonucleotides composed of 2'-O-methyl or 2'-fluoro modified nucleotides are known to be resistant to degradation by mammalian serum nucleases, but we found that some bacterial nucleases can efficiently digest them. We have engineered chemically modified oligonucleotide probes to be specifically activated by nucleases of Mycoplasma fermentans (see Hernandez et al., Nucleic Acid Therapeutics, 2012), Staphylococcus aureus (see Hernandez et al., Nature Medicine, 2014) and Escherichia coli (unpublished). Due to their simplicity of use, and high sensitivity and specificity, these probes may be used to address a variety of unmet clinical needs. With the S. aureus-specific probe, we developed a proof-of-concept study in which we demonstrated the rapid, non-invasive imaging of focal S. aureus infections in mice (see Hernandez et al., Nature Medicine, 2014). Ongoing projects include efforts to translate the probe-based S. aureus detection to clinical practice and to evaluate the potential of E. coli specific probes for various clinical diagnostic endpoints.

Publications

Burghardt, E. L., Flenker, K. S., Clark, K. C., Miguel, J., Ince, D., Winokur, P., Ford, B. & McNamara, 2nd, J. O. (2016). Rapid, Culture-Free Detection of Staphylococcus aureus Bacteremia. PloS one, 11(6), e0157234. PMID: 27305148.

Thiel, W. H., Thiel, K. W., Flenker, K. S., Bair, T., Dupuy, A. J., McNamara, 2nd, J. O., Miller, F. J. & Giangrande, P. H. (2015). Cell-internalization SELEX: method for identifying cell-internalizing RNA aptamers for delivering siRNAs to target cells. Methods in molecular biology (Clifton, N.J.), 1218, 187-99. PMID: 25319652.

Kiedrowski, M. R., Crosby, H. A., Hernandez, F. J., Malone, C. L., McNamara, J. O. & Horswill, A. R. (2014). Staphylococcus aureus Nuc2 Is a Functional, Surface-Attached Extracellular Nuclease. (Vols. 9). (4), pp. e95574. PLoS One.

Hernandez, F. J., Huang, L., Olson, M. E., Powers, K. M., Hernandez, L. I., Meyerholz, D. K., Thedens, D. R., Behlke, M. A., Horswill, A. R. & McNamara, J. O. (2014). Non-invasive Imaging of Staphylococcus aureus Infections with a Nuclease-Activated Probe. Nature Medicine, 20(3), 301-306.

Hernandez, L. I., Flenker, K. S., Hernandez, F. J., Klingelhutz, A. J., McNamara, 2nd, J. O. & Giangrande, P. H. (2013). Methods for Evaluating Cell-Specific, Cell-Internalizing RNA Aptamers. Pharmaceuticals (Basel, Switzerland), 6(3), 295-319. PMID: 23894227.

Gilboa, E., McNamara, 2nd, J. & Pastor, F. (2013). Use of oligonucleotide aptamer ligands to modulate the function of immune receptors. Clinical cancer research : an official journal of the American Association for Cancer Research, 19(5), 1054-62. PMID: 23460536.

Huang, Y. Z., Hernandez, F. J., Gu, B., Stockdale, K. R., Nanapaneni, K., Scheetz, T. E., Behlke, M. A., Peek, A. S., Bair, T., Giangrande, P. H. & McNamara, J. O. (2012). RNA aptamer-based functional ligands of the neurotrophin receptor, TrkB. Molecular pharmacology, 82(4), 623-35. PMID: 22752556.

Hernandez, F. J., Stockdale, K. R., Huang, L., Horswill, A. R., Behlke, M. A. & McNamara, J. O. (2012). Degradation of nuclease-stabilized RNA oligonucleotides in Mycoplasma-contaminated cell culture media. Nucleic acid therapeutics, 22(1), 58-68. PMID: 22229275.

Dassie, J. P., Liu, X. Y., Thomas, G. S., Whitaker, R. M., Thiel, K. W., Stockdale, K. R., Meyerholz, D. K., McCaffrey, A. P., McNamara, J. O. & Giangrande, P. H. (2009). Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors. Nature biotechnology, 27(9), 839-49. PMID: 19701187.

McNamara, J. O., Kolonias, D., Pastor, F., Mittler, R. S., Chen, L., Giangrande, P. H., Sullenger, B. & Gilboa, E. (2008). Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice. The Journal of clinical investigation, 118(1), 376-86. PMID: 18060045.

McNamara, J. O., Andrechek, E. R., Wang, Y., Viles, K. D., Rempel, R. E., Gilboa, E., Sullenger, B. A. & Giangrande, P. H. (2006). Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nature biotechnology, 24(8), 1005-15. PMID: 16823371.

McNamara, J. O. (2003). Transport and function of TGN38. United States – North Carolina: Duke University.