Assistant Professor of Chemistry
Ph.D. Princeton University, 2009
(Analytical, Biological, and Physical Chemistry)
Research in the Fu group focuses on developing novel optical spectroscopy and imaging techniques to investigate the spatial-temporal dynamics of living biological systems at single cell resolution. In particular, we are interested in using label-free spectroscopic imaging approaches such as stimulated Raman scattering microscopy to study the cellular mechanism of complex diseases such as cancer and metabolic disorders. We draw on expertise from multiple disciplines including analytical chemistry, ultrafast spectroscopy, imaging science, optical engineering, bioinstrumentation, cell biology, and systems biology.
Label-free optical microscopy
Optical microscopy, especially fluorescence microscopy, is instrumental in unraveling the intricate biological processes that happen inside living cells. However, most biomolecules in the cell do not fluorescence and visualizing those molecules requires fluorescent tags, which may often be unavailable or perturbative to their biological functions. We develop transient absorption microscopy and stimulated Raman scattering microscopy to directly image biomolecules based on their intrinsic electronic and vibrational contrasts, thus obviating the need for fluorescent labels.
Understanding single cell metabolism
Biological tissues are heterogeneous, made up of cells with distinct expression profiles and unique metabolic dynamics. Single cell analysis represents an emerging class of techniques that allow the study of cell-to-cell variations and how these differences influence development and diseases. Such analyses are currently carried out in isolated cells, lacking critical information about their tissue context and cell-cell or cell-microenvironment interactions. Our goal is to use quantitative optical microscopy to profile the local chemical environments and metabolic dynamics of individual cells within complex tissues such as tumors, which will provide new insights into the mechanisms of disease progression and new ways of therapeutic intervention.
Quantifying drug disposition in living cells
Targeted cancer therapy with small molecule drugs has come to the forefront of cancer treatment. A big challenge in preclinical drug development is that biochemical activity of drugs measured in vitro often do not correlate with drug activity in vivo. One major contribution to the difference between the cellular and biochemical potency of small molecule drugs is the inability to account for drug transport and drug metabolism in cells. Most small molecule drugs are non-fluorescent and thus invisible. We aim to develop the next-generation stimulated Raman scattering microscopy with improved sensitivity and spectral resolution to detect and quantify localized drug concentration in living cells.
Developing early disease diagnosis tools
Cancer at the early stage, when treatment has the highest chance of a complete cure, often eludes the detection with traditional X-ray, ultrasound or MRI imaging. Microscopic examination of H&E stained tissue biopsies has long been the gold standard for cancer diagnosis. However, the undesirability of tissue removal, the long wait time, and a high chance of missing disease tissue necessitate developing optical “virtual biopsy” technology. We will develop new optical spectroscopy and imaging tools for early cancer diagnosis. The same set of tools could also enable diagnosis of many other diseases that involve chemical modifications of tissue such as atherosclerosis.
Francis, A.; Berry, K.; Chen, Y.; Figueroa, B.; Fu, D. Label-free Pathology by Spectrally Sliced Femtosecond Stimulated Raman Scattering (SRS) Microscopy. PLoS One, 2017, 12 (5), e0178750.
Figueroa, B.; Chen, Y.; Berry, K.; Francis, A.; Fu, D. Label-free chemical imaging of latent fingerprints with stimulated Raman scattering microscopy. Anal. Chem. 2017, 89 (8), 4468–4473.
Fu, D.; Yang, W.; Xie, X. S. Label-free Imaging of Neurotransmitter Acetylcholine at Neuromuscular Junctions with Stimulated Raman Scattering. J. Am. Chem. Soc. 2017, 139 (2), 583–586.
Fu, D.; Zhou, J.; Zhu, W.S.; Manley, P.W.; Wang, Y.K.; Hood, T.; Wylie, A.; Xie, X.S. Imaging the intracellular distribution of tyrosine kinase inhibitors in living cells with quantitative hyperspectral stimulated Raman scattering. Nat. Chem. 2014, 6, 614–622.
Fu, D.; Yu, Y.; Folick, A.; Currie, E.; Farese, R.V.; Tsai, T.-H.; Xie, X.S.; Wang, M.C. In Vivo Metabolic Fingerprinting of neutral lipids with hyperspectral stimulated Raman scattering microscopy. J. Am. Chem. Soc. 2014, 136, 8820–8828.