Dr. Aaron Joseph Lucero Villaraza
Position: Associate Professor
Education: Ph.D. (Chemisty), Manchester University (UK), 2008
Radioimmune and Inorganic Chemistry Section
Radiation Oncology Branch, National Cancer Institute
National Institutes of Health, USA
Development of fluorescent polymer-antibody conjugates for cancer imaging
My research interests revolve around the development of molecular probes (small molecule to macromolecular) as tools for in vitro assays and contrast agents for in vivo medical imaging (MRI, optical, PET, SPECT). In particular, I have designed strategies for the synthesis of polyheterometallic lanthanide chelates as potential contrast agents for multi-modal (MRI/optical) imaging protocols. Some lanthanides, such as Eu3+, Tb3+ and Yb3+, exhibit large Stokes shift and sharp, atom-like emission spectra with emission lifetimes ranging from the us to ms timescale, spectral characteristics which are an advantage in in vitro optical imaging. Gd3+ is a highly paramagnetic ion which dramatically enhances the NMR relaxation rate of 1H-nuclei of water molecules bound to it, making it the best choice among the lanthanides for MRI applications. I have also worked on the synthesis of fluorescent polymer-antibody bioconjugates for optical detection of cancer cells over-expressing the epidermal growth factor receptor HER1. At present, I am interested in extending these concepts to the labeling and bioconjugation of small molecule natural products with known molecular targets to the synthesis of large, synthetic polymers or polymer-biomolecular hybrids for applications in cancer diagnosis, microbiology, and neuroscience.
1.) “Synthesis and Spectroscopic Studies on Azo-Dye Derivatives of Polymetallic Lanthanide Complexes: Using Diazotization to Link Metal Complexes Together” Placidi, M.P.; Villaraza, A.J.L.; Natrajan, L.S.; Sykes, D.; Kenwright, A.M.; Faulkner, S. J. Am. Chem. Soc. 2009, 131, 9916-9917.
2.) “Controlled Preparation of a Heterometallic Lanthanide Complex Containing Different Lanthanides in Symmetrical Binding Pockets” Natrajan, L.S.; Villaraza, A.J.L.; Kenwright, A.M.; Faulkner, S. Chem. Commun. 2009, 40, 6020-6022.
3.) “Macromolecules, Dendrimers and Nanomaterials in Magnetic Resonance Imaging: The Interplay Between Size, Function and Pharmacokinetics” Villaraza, A.J.L.; Bumb, A.; Brechbiel, M.W. Chem. Rev. 2010, 110, 2921-2959.
4.) “Improved Speciation Characteristics of PEGylated Indocyanine Green-Labeled Panitumumab: Revisiting the Solution and Spectroscopic Properties of a Near-Infrared Emitting anti-HER1 Antibody for Optical Imaging of Cancer” Villaraza, A.J.L.; Milenic, D. E.; Brechbiel, M.W. Bioconjugate Chem. 2010, 21, 2305-2312.
5.) “A Bacterial Source for Mollusk Pyrone Polyketides” Lin, Z.; Torres, J.P.; Ammon, M.A.; Marret, L.; Teickert, R.W.; Reilly, C.A.; Kwan, J.C.; Tianero, M.D.; Peraud, O.; Cox, J.E.; Light, A.R.; Villaraza, A.J.L.; Haygood, M.G.; Concepcion, G.P.; Olivera, B.M.; Schmidt, E.W. Chem. Biol. 2013, 20, 73-81.
6.) “Ion Charge Density Governs Selectivity in the Formation of Metal-Xylenol Orange (M-XO) Complexes” Belleza, O.V.; Villaraza, A.J.L. Inorg. Chem. Commun. 2014, 47, 87-92.
7.) “Synthesis and Bioactivity of Nobilamide B” Jacinto, M.P.V.; Flores, M.S.; Lin, Z.; Concepcion, G.P.; Schmidt, E.W.; Faulkner, S.; Villaraza, A.J.L. RSC Adv. 2014, 4, 37609-37612.
8.) “Gd-XO: a colourimetric probe for the complexation of Gd3+ with DO3A-type ligands” Suazo, K.F.G.; Villaraza, A.J.L. Anal. Methods 2015, 7, 8967-8969.