The Lippert Research Group

The Lippert lab is a highly collaborative and interdisciplinary group that applies innovative organic chemistry to address key challenges in molecular imaging, focusing on the development of biocompatible imaging agents. These newly developed probes will provide unique tools and clinical diagnostics to study cellular chemistry important in aging, cancer, cardiovascular disease, and neuronal signaling, with a particular emphasis on the roles and interactions of reactive sulfur, oxygen, nitrogen, and carbon species.

Illuminating Cellular Chemistry with Fluorescence Imaging

The living cell is a magnificently orchestrated molecular system that uses precisely controlled chemistry to interact with its environment and control its inner workings. The details of this chemistry are exquisitely challenging to study in a test tube, and understanding these processes in living cells requires methods for real time visualization. We design highly chemoselective transformations that are operative inside of living organisms and use streamlined synthetic protocols for the preparation of fluorescence microscopy imaging probes. Our particular interest lies in developing methods to detect and image reactive small molecule species derived from sulfur, oxygen, nitrogen, and carbon. Organic synthesis and reaction methodology are core technologies utilized in our lab, which we use both to develop new types of imaging agents as well as optimize and characterize existing agents. Untangling the details of cellular chemistry will require a combination of imaging agents and techniques and students in my lab learn a diverse set of skills ranging from organic synthesis to cellular biology.

Collaborators:
Prof. Peng Tao, Department of Chemistry, SMU
Prof. Thomas Ritz, Department of Clinical Psychology, SMU
Prof. Johannes Bauer, Department of Biology, SMU

Bruemmer, K. J.; Merrikhihaghi, S.; Lollar, C. T.; Morris, S. N. S.; Bauer, J. H.; Lippert, A. R. "19F Magnetic Resonance Probes for Detecting Peroxynitrite in Living Cells Using an Oxidative Decarbonylation Reaction." Chem. Commun. 2014 , 50, 12311. doi: 10.1039/C4CC04292A
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Lollar, C. T.; Krenek, K. M.; Bruemmer, K.J.; Lippert, A. R. "Ylide Mediated Carbonyl Homologations for the Preparation of Isatin Derivatives." Org. Biomol. Chem. 2014 , 12, 406. doi: 10.1039/C3OB42024H.
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Lin, V. S.; Lippert, A. R.; Chang, C. J. "Cell-trappable fluorescent probes for endogenous hydrogen sulfide signaling and imaging H2O2-dependent H2S production." Proc. Natl. Acad. Sci. USA 2013 , 110, 7131. doi: 10.1073/pnas.1302193110 (Highlighted in the April 22 issue of Chemical & Engineering News)
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Triggered Energy Transfer Chemiluminescence for In Vivo Imaging

Chemiluminescence, the generation of light from a chemical reaction, does not require an excitation source and eliminates autofluorescence and light scattering that is endemic to fluorescence imaging. Indeed, bioluminescence, one type of chemiluminescence that uses an enzymatic reaction to produce light, has become a powerful pre-clinical imaging technique, but requires genetically modified animals that express bioluminescent enzymes. In order to circumvent this key obstacle and open up the possibility of preclinical imaging of wild-type animals and ultimately clinical chemiluminescent imaging, our lab is developing innovative triggered energy transfer chemiluminescence agents for imaging a range of molecular markers. We are also using triggered chemiluminescence for low cost detection platforms that interface with widely available smart-phone technology.

Collaborators:
Prof. Ralph Mason, Department of Radiology, UTSW
Prof. Thomas Ritz, Department of Clinical Psychology, SMU
Prof. David Son, Department of Chemistry, SMU
Prof. Ali Beskok, Department of Mechanical Engineering, SMU

Cao, J.; Lopez, R.; Thacker J. M.; Moon, J. Y.; Jiang, C.; Morris, S. N. S.; Bauer, J. H.; Tao, P.; Mason, R. P.; Lippert, A. R.* "Chemiluminescent Probes for Imaging H2S in Living Animals." Chem. Sci. 2015 in press. doi: 10.1039/C4SC03516J.
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Quimar, M.; Krenek, K. M.; Lippert, A. R. "Multiplexed point-of-care chemiluminescent imaging of reactive species using a smartphone camera" in preparation.
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