Biosciences Graduate Program

James McNamara, PhD

Portrait

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

Contact Information

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

Lab: 3256 CBRB
Iowa City, IA 52242

Email: james-mcnamara@uiowa.edu

Education

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

Post Doctoral, Duke University Medical Center

Education/Training Program Affiliations

Biosciences Graduate Program
Interdisciplinary Graduate Program in Molecular and Cellular Biology
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Acid Therapeutics, 2012), Staphylococcus aureus (see Hernandez et al., Nature Medicine, 2014) and Escherichia coli (unpublished).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.

Selected Publications

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

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

Huang Y, Hernandez F, Gu B, Stockdale K, Nanapaneni K, Scheetz T, Behlke M, Peek A, Bair T, Giangrande P, McNamara J.  RNA aptamer-based functional ligands of the neurotrophin receptor, TrkB..  Molecular pharmacology.  2012 October. 82(4):623-35.
[PubMed]

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

Dassie J, Liu X, Thomas G, Whitaker R, Thiel K, Stockdale K, Meyerholz D, McCaffrey A, McNamara J, Giangrande P.  Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors..  Nature biotechnology.  2009 September. 27(9):839-49.
[PubMed]

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

McNamara J, Andrechek E, Wang Y, Viles K, Rempel R, Gilboa E, Sullenger B, Giangrande P.  Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras..  Nature biotechnology.  2006 August. 24(8):1005-15.
[PubMed]

Date Last Modified: 10/16/2014 - 11:10:40