Research

The work in this laboratory is multidisciplinary and encompasses organic synthesis, molecular design, biophysical methods, fluorescence microscopy, and animal imaging. As a result, the students receive broad training and the individual research topics are quite varied. Shown below is a sampling of some recent projects:


  • Small Molecule Probes for Molecular Imaging
  • Fluorescence Imaging of Cancer
    • We have developed near-IR fluorescent probes that can localize to a variety of tumors allowing for their detection in living mice.

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  • Fluorescence Imaging of Bacterial Infection Models
    • Bacterial Infection Imaging Using a Fluorescent Probe
      • Optical images of a mouse with a S. aureus infection in the left rear thigh muscle. Images were acquired before (A), and immediately following (B), intravenous injection of fluorescent probe, and at 6 h (C), 12 h (D), 18 h (E), and 21 h (F).

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  • Bacterial Infection Imaging Using Quantum Dot Probe
    • A Near-IR quantum dot probe that is coated with zinc DPA ligands can target bacteria and be observed in a living mouse.

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  • Squaraine-Rotaxanes as Novel Near-IR Dyes
    • Progress in the field of in vivo optical imaging will be greatly accelerated by the invention of new Near-IR fluorophores with improved performance in biological media. We have recently developed a series of novel squaraine-rotaxanes that are completely stable in serum. The utility of these Near-IR dyes will be demonstrated by conjugating them to cancer targeting ligands and employing the conjugates in optical imaging protocols.

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  • Fluorescence microscopy images of live CHO cells treated with Hochest 33342 (A), Squaraine Rotaxane (B), and FM1-43 (C). Panel D is the resulting overlay from A, B, and C.


  • Sensors of Cell Apoptosis
    • We have recently discovered a series of small molecules that can sense the presence of phosphatidylserine on the surface of cells. These compounds can be used to detect cell apoptosis. The sensors can be employed in a wide range of cell biology reserach projects and also help with the discovery of anticancer drugs. Also we plan to develop the sensors into in vivo imaging agents of dying tissue.
      • Cells stained and imaged with contrast agents (A,B,C) and (D) bright-field image show apoptotic cells in the circled regions

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  • Cell Penetrating Peptides
    • A zinc coordinated oligotyrosine acts as a cell penetrating peptide and delivers dyes and protein cargo into cells.

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Videos of Fluorescent Imaging using Squaraine Rotaxanes

  • Eukaryotic Cells
    • Live eukaryotic mammalian cells are treated with Squaraine Rotaxaes. This particular dye labels internal compartments of the cell known as endosomes. The stability and brightness of this dye allows one to readily examine these events in real time for extended periods of time.

http://www.youtube.com/v/xDIEMYagU3E?fs=1&hl=en_US&rel=0&border=1


  • Vesicle Tracking Along the Tubulin Network in a Living Cell
    • Short video of endosomes labeled with a water soluble squaraine rotaxane dye tracking along the tubulin network of a living eukaryotic cell. The tubulin network is labeled via expression of GFP alpha tubulin. The nucleus of the cell is labeled with H33342. This video was made on a Nikon TE-2000U epifluorescence microscope. The acquired video was then processed and prepared using ImageJ. This video is in real time.

http://www.youtube-nocookie.com/v/CDWoOOd_VHo?fs=1&hl=en_US&rel=0&border=1


  • Eukaryotic Endoplasmic Reticulum
    • This video shows a brief, real time stream of a treated live Chinese hamster ovary (CHO) cells. The movements of the cellular structures in this video are suddle so you may have to view it several times to catch their dynamics. This particular version of the dye specifically partitions into the membranes of these CHO cells, allowing for detailed imaging of this cellular structure.

http://www.youtube-nocookie.com/v/mrMCAF2_ywg?fs=1&hl=en_US&rel=0&border=1


  • Bacterial Binary Fission
    • Live gram negative bacterial cells are treated with Squaraine Rotaxanes. This particular dye labels the membrane of bacterial cells. The stability and brightness of this dye allows one to readily examine bacterial binary fission in real time for extended periods of time.

http://www.youtube-nocookie.com/v/SLpFJ1JeRYs?fs=1&hl=en_US&rel=0