Revealing hidden signatures in biological systems

2.1 Single-cell cancer metabolism

By label-free spectroscopic imaging of patient specimens, my team discovered an aberrant storage of cholesteryl ester (CE) in aggressive human prostate cancer (Cell Metabolism 2014). This study identified a novel target that can be used to treat late-stage human prostate cancer (US patent 9,164,084 B2) through a nanomedicine formulation (ACS Nano 2015). More recently, we identified lipid unsaturation as a metabolic marker of ovarian cancer stem cells (Cell Stem Cell 2017), which paves the foundation for suppression of cancer stem cells.

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Representative publications:

Shuhua Yue, Junjie Li, Seung-Young Lee, Hyeon Jeong Lee, Tian Shao, Bing Song, Liang Cheng, Timothy A. Masterson, Xiaoqi Liu, Timothy L. Ratliff, Ji-Xin Cheng*, Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metabolism, 2014 March, 18: 393-406. Highlighted by Nature & Cancer Discovery.

Seung-Young Lee, Junjie Li, Jien Nee Tai, Timothy L. Ratliff, Kinam Park, Ji-Xin Cheng*, Cholesterol esterification-blocking nanomedicine for selective cancer chemotherapy, ACS Nano, 2015, 3: 2420-32.

Junjie Li, Salvatore Condello, Jessica Thomes-Pepin, Xiaoxiao Ma, Yu Xia, Thomas D Hurley, Daniela Matei*, Ji-Xin Cheng*, Lipid Desaturation Is a Metabolic Marker and Therapeutic Target of Ovarian Cancer Stem Cells, Cell Stem Cell, 2017, 20: 303-314.

2.2 Myelin sheath de-/re-generation and functional recovery of injured spinal cord

Our laboratory was the first to show label-free CARS imaging of myelin sheath in its natural state [4](Biophys J 2005, 89: 581-591), now pursued by different groups. This work, funded by an NIH R01 grant (2005-2008), led to our recent development of a nanomedicine for functional recovery of an injured spinal cord [5] (Nature Nanotechnology 2010, 5: 80-87), and is supported by a translational research award from the Coulter Foundation.

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Representative publications:

Wei Wu, Seung-Young Lee, He Wang, Pu Wang, Delong Zhang, Zheng Ouyang, Kinam Park, Xiao-Ming Xu*, Ji-Xin Cheng*, Functional restoration of traumatically injured spinal cord by glycol chitosan nanoparticles in a clinically relevant time window. Biomaterials, 2014, 35:2355-64.

Yunzhou Shi, Sungwon Kim, Terry B. Huff, Richard Borgens, Kinam Park, Riyi Shi, Ji-Xin Cheng*, “Block copolymer micelles effectively repair traumatically injured spinal cord white matter,” Nature Nanotechnology, 2010, 5: 80-87.

Wang, Y. Fu, P. Zickmund, R. Shi, J.X. Cheng*, “Coherent anti-Stokes Raman scattering imaging of live spinal tissues,” Biophys. J., 2005, 89:581-591.

2.3 Label-free spectroscopic imaging of membrane potential in living neurons

Detecting membrane potentials is critical for understanding how neuronal networks process information. We report a vibrational spectroscopic signature of neuronal membrane potentials identified through hyperspectral stimulated Raman scattering (SRS) imaging of patched primary neurons. High-speed SRS imaging allowed direct visualization of puff-induced depolarization of multiple neurons in mouse brain slices, confirmed by simultaneous calcium imaging. The observed signature, partially dependent on voltage-gated sodium channels, is interpreted as an ion-induced uncoupling of Fermi resonance. By implementing a dual-SRS balanced detection scheme, we detected single action potentials in electrically stimulated neurons. These results collectively demonstrate the potential of sensing neuronal activities at multiple sites with a label-free vibrational microscope.

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Representative publications:

Hyeon Jeong Lee, Delong Zhang, Ying Jiang, Xiangbing Wu; Pei-Yu Shih, Chien-Sheng Liao; Brittani Bungart;  Xiao-Ming Xu; Ryan Drenan; Edward Barlett, Ji-Xin Cheng*, “Label-free vibrational spectroscopic imaging of neuronal membrane potential”, Journal of Physical Chemistry Letters, 2017, 8: 1932-1936.

2.4 Antibiotic susceptibility determination within one cell cycle at single bacterium level

The widespread use of antibiotics has significantly increased the number of resistant bacteria, which has also increased the urgency of rapid bacterial detection and profiling their antibiotics response. Current methods for antibiotic susceptibility testing (AST) require at least 16 to 24 h to conduct. Therefore, there is an urgent need for a rapid method that can test the susceptibility of bacteria in a culture-free manner. Here we demonstrate a rapid AST method by monitoring the glucose metabolic activity of live bacteria at the single cell level with hyperspectral stimulated Raman scattering imaging.

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Representative publications:

Caroline W. Karanja, Weili Hong, Waleed Younis, Hassan E. Eldesouky, Mohamed N. Seleem*, Ji-Xin Cheng*. Stimulated Raman Imaging Reveals Aberrant Lipogenesis as a Metabolic Marker for Azole-resistant Candida albicans, Analytical Chemistry, 2017