1992 - 1996  Central China Normal University, B.S. in Chemical Education, Wuhan, China

1996 - 2000  Central China Normal University, M.S. in Organic Chemistry, Wuhan, China

2000 - 2004  Huazhong University of Science and Technology, Ph.D. in Engineering of Biomedicine, Wuhan, China

2004 - 2006  Postdoctoral Fellow, Assistant Professor,Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

2006 - 2010  Associate Professor, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

2010 - 2020  Professor, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

2020 -           Tenured Professor, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

2008  The State Natural Science Award (the second class), P.R.CHINA

2009  Lu Jiaxi Young Talent Award from Chinese Academy of Sciences

1. Super-resolution microscopy probes, methods and visualization studies of important biological processes.

Super-resolution microscopy imaging technology can break through the diffraction limit and provide nano-scale positioning and structural information of biological macromolecules. It is a research hotspot and development trend in the field of biological imaging, and provides new possibilities for solving many problems in the field of life sciences. This technology won the 2014 Nobel Prize in Chemistry.

Optical instruments, fluorescent probes and algorithms are three important directions in the field of super-resolution imaging. We are committed to the innovative research of super-resolution imaging probes and methods, and improve the spatio-temporal resolution of imaging by developing new fluorescent protein probes and imaging methods. We are the first domestic research group focused on the development of super-resolution imaging probes, and we have made systematic and internationally leading research achievements in the field of super-resolution imaging with fluorescent probes. These achievements not only provide the best imaging tools for the current super-resolution imaging technologies, but also greatly improve the temporal and spatial resolution and biological applications of these imaging methods.

Our group has developed a variety of fluorescent protein probes for the current commonly used super-resolution imaging methods. For example, we have developed the first fluorescent protein that can maintain fluorescence under traditional electron microscope sample preparation. With this protein ,we get the first high-precision Correlative Light & Electron Microscopy image of the same-layer slices while maintaining the ultrastructure of biological samples to the greatest extent. This achievement promotes the application of high-precision three-dimensional photoelectric correlation imaging in large-scale thick samples (such as brain tissue) (Nature Methods, 2020). We have developed suitable fluorescent protein probes for multiple super-resolution imaging technologies such as PALM/STORM, SOFI, NL-SIM, etc., which greatly improves the temporal and spatial resolution of imaging. Among them, mEos3.2 (Nature Methods, 2012) and Skylan-S (ACS Nano, 2015) are the gold standard probes for single-molecule localization imaging and SOFI imaging, respectively. Our Skylan-NS combined with PA NL-SIM technology, the spatial resolution of super-resolution imaging of live cells has been increased from 100 nm to 45 nm for the first time (PNAS, 2016). The super-resolution probes developed by our team are almost all the "star" probes of a variety of current super-resolution imaging technologies. The excellent properties of these probes have been unanimously recognized by international counterparts, and have been widely used in research fields such as ubiquitination degradation, telomerase function, cell division, virus resistance, and channel composition of nerve cells by more than 200 laboratories at home and abroad.We have also developed a new method for super-resolution imaging of live cells based on single-molecule localization. We have developed SIMBA (Cell Research, 2017) and Quick-SIMBA (Nano Letters, 2020) new methods, combined with the self-developed pcStar probe, to increase the temporal and spatial resolution of live cell imaging to 0.1 s and 50 nm. Therefore, super-resolution imaging based on single-molecule localization advances from fixed cells to living cells. We also developed the Hessian single-molecule localization SR imaging method (Biophysics Reports, 2018), which can effectively remove sCMOS pixel-dependent readout noise and improve the spatio-temporal resolution of single-molecule localization SR imaging. The top methodological journal Nature Methods conducted a special interview with researcher Xu Pingyong in 2018. In the interview, a large amount of space introduced our group's achievements and viewpoints in the development of fluorescent proteins to improve the spatio-temporal resolution of super-resolution imaging. This is the first special interview with a domestic scientist on Nature Methods.

In addition to developing probes that can be used for super-resolution imaging, we also develop functional probes with excellent performance. We have developed the best-performing red pH-sensitive fluorescent protein pHmScarlet so far, which has achieved simultaneous detection and super-resolution imaging of vesicle anchoring and secretion steps (Nature Communication, 2021). We have also developed a calcium function probe for subcellular organelle localization, which can simultaneously detect calcium concentration and localization.

At present, our group is mainly focused on the development of a new generation of fluorescent protein probes that can be used in live cell ultra-high resolution microscopic imaging technology, and fluorescent probes that can be applied to Correlative Light & Electron Microscopy. Moreover, based on the development of new probes, the ultra-high resolution microscopic imaging technology of living cells with higher spatial and temporal resolution is developed, and their application in cell biology is explored. In addition, in order to be able to perform imaging in deeper tissues, our research group is developing high-throughput screening equipment and methods for two-photon fluorescent proteins, to carry out the screening and evolution of two-photon fluorescent proteins.

The probes and methods we developed will eventually be used to visualize important biological processes in cells. We will focus on application research in two directions: neuronal activity detection and loop tracing, chromatin structure and expression regulation.At present, the application of ultra-high resolution methods in the field of neuroscience to study protein localization and related functions is still at an early stage, and the probes and methods for characterizing neuronal activity need to be further developed. Our group will use our advantages in fluorescent protein modification technology and methods to develop new probes and methods for characterizing neuronal activity, and conduct ultra-high-resolution imaging positioning and functional research in neurons. The dynamic changes of chromatin structure are closely related to the occurrence of diseases. Another important biological scientific issue of our group is the study of chromatin structure and gene expression regulation based on the development of super-resolution imaging probes, live-cell super-resolution imaging methods, and Correlative Light & Electron Microscopy.

2. Protein evolution, detection and activity manipulation.

The quantity/concentration and activity of the protein are essential for its function. The development of highly sensitive probes and methods is an effective means to detect the quantity/concentration of proteins and characterize their localization and activity in cells. In addition, low-cost/micro blood sample/multi-protein detection technology has extremely wide applications in clinical testing, and can be used by the majority of hospitals to detect infectious microorganisms/tumor markers/disease diagnosis and typing, etc.

We will develop high-throughput nanobody preparation technology on the basis of the previous fluorescent protein evolution technology. And we will develop high-sensitivity and micro-protein detection technology based on nano antibodies, as well as protein activity manipulation technology, to achieve the detection and activity regulation of proteins in clinical samples and living cells.

3. Study on the molecular mechanism of metabolic diseases.

Kidney disease is a common high-incidence disease in children and adults clinically. Podocytes are a kind of key cell in the glomerulus. Its structure and function are essential to the function of the glomerulus. The structure and function of the podocytes often lead to the occurrence of nephropathy. The cytoskeleton plays an important role in the function of podocytes and the hierarchical structure of the glomerulus. With positioning and functional probes, super-resolution imaging and other technologies, we will study the clinically high incidence of kidney diseases, search for and discover new diagnostic markers, and use them for the precise classification of kidney diseases with different clinical manifestations, and study the possibilities mechanism of pathogenicity.

The liver is the metabolic center of the human body and has many important functions such as detoxification, secretion, and immune regulation. Dysfunction of the liver can cause hepatitis, fatty liver, liver cancer and other diseases. In addition, the liver is closely related to many other diseases. We will establish and develop time-resolved liver secretomics detection technology to study the effects of hunger and fullness, different diets and other nutritional status, liver pathological conditions, and other diseases on liver secretion and function.

1. Fu, Z., Peng, D., Zhang, M., …& Xu, T.*, Xu, P.* (2020). mEosEM withstands osmium staining and Epon embedding for super-resolution CLEM. Nature methods, 17(1), 55-58.

2. Zhang, M., Fu, Z., Li, C., Liu, A., Peng, D., Xue, F., ... & Xu, T.*, Xu, P.* (2020). Fast super-resolution imaging technique and immediate early nanostructure capturing by a photoconvertible fluorescent protein. Nano letters, 20(4), 2197-2208. (Cover)

3. Pei X, Wang Z, He W, et al. ER-tethered RNA-binding protein controls NADPH oxidase translation for hydrogen peroxide homeostasis[J]. Redox Biology, 2024, 71: 103126.

4. Liu, A., Huang, X., He, W., Xue, F., Yang, Y., Liu, J., ...Lin Y.* & Xu P*. (2021). pHmScarlet is a pH-sensitive red fluorescent protein to monitor exocytosis docking and fusion steps. Nature communications, 12(1), 1-12.

5. Xue F, He W, Peng D, et al. SOGO-SOFI, light-modulated super-resolution optical fluctuation imaging using only 20 raw frames for high-fidelity reconstruction[J]. Fundamental Research, 2023.

6 Peng D, Li N, He W, et al. Improved fluorescent proteins for dual-colour post-embedding CLEM[J]. Cells, 2022, 11(7): 1077.

7. Pei X, Wang H, Xu P, et al. The core autophagy protein ATG5 controls the polarity of the Golgi apparatus and insulin secretion of pancreatic beta cells[J]. Biochemical and Biophysical Research Communications, 2022, 629: 26-33.

8. Yuan, L., Liu, Q., Wang, Z., Hou, J., & Xu, P*. (2019). EI24 tethers endoplasmic reticulum and mitochondria to regulate autophagy flux. Cellular and Molecular Life Sciences, 2019 Jul 22. doi: 10.1007/s00018-019-03236-9.

9. Yuan, L., Wang, H., Liu, Q., Wang, Z., Zhang, M., Zhao, Y., ... & Xu, T.*, Xu, P.* (2018). Etoposide-induced protein 2.4 functions as a regulator of the calcium ATPase and protects pancreatic β-cell survival. Journal of Biological Chemistry, 293(26), 10128-10140.

10. Xu, F., Zhang, M., He, W., Han, R., Xue, F., Liu, Z., Zhang, F.*, Lippincott-Schwartz, J.*, Xu, P.* (2017). Live cell single molecule-guided Bayesian localization super resolution microscopy. Cell research, 27(5), 713.

11. Zhang, X., Zhang, M., Li, D., He, W., Peng, J., Betzig, E.*, & Xu, P*. (2016). Highly photostable, reversibly photoswitchable fluorescent protein with high contrast ratio for live-cell superresolution microscopy. Proceedings of the National Academy of Sciences, 113(37), 10364-10369.

12. Du, W., Zhou, M., Zhao, W., Cheng, D., Wang, L., Lu, J., ... & Xue, Y.H.*, Xu, P.*, Xu, T.*(2016). HID-1 is required for homotypic fusion of immature secretory granules during maturation. Elife, 5, e18134.

13. Zhang, X., Chen, X., Zeng, Z., Zhang, M., Sun, Y., Xi, P.*, Peng, J.*, Xu, P.* (2015). Development of a reversibly switchable fluorescent protein for super-resolution optical fluctuation imaging (SOFI). ACS nano, 9(3), 2659-2667.

14. Chen, J. J., Jing, J., Chang, H., Rong, Y., Hai, Y., Tang, J., Zhang, J.*, Xu, P.* (2013). A sensitive and quantitative autolysosome probe for detecting autophagic activity in live and prestained fixed cells. Autophagy, 9(6), 894-904.

15. Jing, J., Chen, J. J., Hai, Y., Zhan, J., Xu, P.*, & Zhang, J. L.* (2012). Rational design of ZnSalen as a single and two photon activatable fluorophore in living cells. Chemical Science, 3(11), 3315-3320.

16. Zhang, M., Chang, H., Zhang, Y., Yu, J., Wu, L., Ji, W., ... & Zhang, J., Xu, P.*, Xu, T.* (2012). Rational design of true monomeric and bright photoactivatable fluorescent proteins. Nature methods, 9(7), 727.

17. Chang, H., Zhang, M., Ji, W., Chen, J., Zhang, Y., Liu, B., ... & Xu, P.*, Xu, T.* (2012). A unique series of reversibly switchable fluorescent proteins with beneficial properties for various applications. Proceedings of the National Academy of Sciences, 109(12), 4455-4460.

18. Hai, Y., Chen, J. J., Zhao, P., Lv, H., Yu, Y., Xu, P.*, Zhang, J. L.* (2011). Luminescent zinc salen complexes as single and two-photon fluorescence subcellular imaging probes. Chemical Communications, 47(8), 2435-2437.　

19. Ji, W., Xu, P., Li, Z., Lu, J., Liu, L., Zhan, Y., Hille, B.*, Xu, T.*, Chen L. *(2008). Functional stoichiometry of the unitary calcium-release-activated calcium channel. Proceedings of the National Academy of Sciences, 105(36), 13668-13673. (Pingyong Xu as co-first author)

20. Bai, L., Wang, Y., Fan, J., Chen, Y., Ji, W., Qu, A., Xu, P.*, James, D.E., Xu, T. (2007). Dissecting multiple steps of GLUT4 trafficking and identifying the sites of insulin action. Cell metabolism, 5(1), 47-57.

Patents

1. A Bayesian microscopy imaging method. (Patent No.: ZL201610282305.5)

2. A light modulated fluorescent protein. (Application number: 201910486631.1)

(From Pingyong Xu, September 14, 2024)