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Lingyan Shi is an Associate Professor in the Shu Chien-Gene Lay Department of Bioengineering in Jacobs School of Engineering, University of California, San Diego (UC San Diego).

Shi is most known for her work on optical techniques in neuroscience, aging, and cancer studies, including the discovery of the Golden Optical Window for deep brain imaging, development of A-POD & PRM enhanced multiplex DO-SRS imaging platforms for imaging metabolic activities in situ.

Shi is the recipient of the 2024 Davos Summit iCANX Young Scientist Award, 2024 BMES-CMBE Rising Star Young Faculty Award, 2023 Sloan Research Fellow Award by Alfred P. Sloan Foundation (in Chemistry), Scialog Fellow Award by CZI, the 2021 Rising Star Award from both Nature Light Science & Applications and Laser Focus World, and the 2018 Blavatnik Regional Awards for Young Scientists; she has also been featured in the 2025 Women in Optics notebook.

Career

After earning her PhD in biomedical engineering, Shi worked as a postdoctoral researcher at the Institute for Ultrafast Spectroscopy and Lasers (IUSL, CCNY) from 2014 to 2016, and then transitioned to Columbia University Chemistry Department from 2016 to 2019. In 2019, she joined the Jacobs School of Engineering at UC San Diego as an Assistant Professor of Bioengineering, Her research lab focuses on the innovation and application of laser scanning multimodal microscopy and spectroscopy technologies.

Shi holds patents for inventions, including a compact optical analyzer that detects viruses and bacteria using advanced lasers and LEDs. She developed a method for deuterium incorporation via heavy water to measure biomolecular levels with Raman spectroscopy, aiding drug efficacy evaluation. Additionally, she created a nonlinear optical process to enhance signals in SRS microscopy through Resonant Stimulated Raman Scattering, improving imaging of vibrational states in cancer tissues.

Research

Shi's research has focused on developing advanced high-resolution Optical spectrometer and imaging platforms that integrate SRS, MPF, SHG, and FLIM into a single piece of microscopy. Her 2016 study made the discovery of the "Golden Optical Window"—a band of infrared wavelengths that penetrates biological tissues more deeply than other wavelengths, increasing imaging depth in brain tissue by up to 50%. This work received media coverage and was featured in Phys.org, and the Novus Light. In 2017, she investigated label-free fluorescence spectroscopy to detect early Alzheimer's disease by comparing the emission spectral profiles of tryptophan and NADH in mouse brain samples, which revealed significant differences between AD and normal tissues and was also highlighted in Laser Focus World magazine. In related research, she used a Stimulated Raman scattering (SRS) imaging platform from her lab to uncover altered lipid metabolism in Alzheimer's disease and identify a new strategy for targeting it with existing and novel drugs, a finding covered by SciTechDaily and Lab Manager Magazine.

Through her 2018 work, Shi developed the DO-SRS microscopy platform, offering a noninvasive approach to imaging metabolic dynamics in living animals. She highlighted that the STRIDE microscopy technique effectively captured the spatial and temporal dynamics of glucose-derived macromolecules in various mouse tissues, contributing to the understanding of glucose metabolism and its anabolic utilization.

Shi introduced a high-throughput mid-infrared metabolic imaging framework using heavy water, enabling detailed metabolic profiling at the single-cell and tissue levels in 2020. This offered spectral information and characterized metabolic heterogeneity across various biological systems. She further demonstrated how this new optical imaging platform can be utilized with multiple SRS microscopy to investigate diets regulated lipid metabolism and aging in Drosophila and mouse models, revealing interactions with insulin signaling pathways and AMPK. Her group's research contributions include the development of A-PoD, a deconvolution algorithm that enhanced SRS imaging resolution, enabling the study of lipid droplets, metabolic dynamics, and differentiation of newly synthesized lipids in Drosophila brain samples across various diets.

Shi's Lab research developed SRS microscopy into a super-resolution multiplex nanoscopy by developing the Adam optimization-based Pointillism Deconvolution (A-PoD) and penalized reference matching (PRM-SRS) algorithms.

Works

Shi edited the book Deep Imaging in Tissue and Biomedical Materials: Using Linear and Nonlinear Optical Methods in 2017, which examined advanced optical imaging techniques with ultrafast lasers and nonlinear processes for safe, noninvasive deep tissue imaging in biomedical diagnostics. David L. Andrews, in his review of the book, remarked, "This impressive volume represents a landmark publication on the use of optical methods for deep biomedical imaging―a field that has been transformed by a variety of technical innovations in recent years". In 2018, she served as the editor of Neurophotonics and Biomedical Spectroscopy, which explored advanced optical techniques for non-invasive disease detection, focusing on tissue changes related to cancer and Alzheimer's while emphasizing neurophotonics in the study of nerve tissue and brain biochemistry.

Awards and honors

• 2013 – Women's Leadership Summit, New York Times and Hunter College
• 2016 – Engineering Outreach Award, 21st Century Foundation
• 2016 – "Beacon" Honorees in "Researcher/Leadership", Photonics Spectra
• 2018 – Blavatnik Regional Award for Young Scientists, New York Academy of Sciences
• 2021 – Hellman Fellow, Society of Hellman Fellows
• 2021 – Rising Stars Awards, Laser Focus World
• 2023 – Advanced Imaging Scialog Fellow, RCSA and the Chan Zuckerberg Initiative
• 2023 – Sloan Research Fellow Award in Chemistry, Alfred P. Sloan Foundation
• 2023 – David L. Williams Lecture and Scholarship Award, Kern Lipid Conference
• 2024 – Davos Summit iCANX Young Scientist Award, Davos Summit
• 2024 – Speaker of China-America Frontiers of Engineering symposium at National Academy of Engineering
• 2024 – BMES-CMBE Rising Star Young Faculty Award, Cell and Molecular Bioeng Society
• 2024 – Optics Notebook: Women in Optics, 20th-anniversary of SPIE notebook

Bibliography

Books

• Deep Imaging in Tissue and Biomedical Materials (2017) ISBN 9781351797382
• Neurophotonics and Biomedical Spectroscopy (2018) ISBN 9780323480673

Selected articles

• Shi, L., Sordillo, L. A., Rodríguez‐Contreras, A., & Alfano, R. (2016). Transmission in near‐infrared optical windows for deep brain imaging. Journal of biophotonics, 9(1-2), 38-43.
• Shi, L., Zheng, C., Shen, Y., Chen, Z., Silveira, E. S., Zhang, L., ... & Min, W. (2018). Optical imaging of metabolic dynamics in animals. Nature communications, 9(1), 2995.
• Zhang, L., Shi, L., Shen, Y., Miao, Y., Wei, M., Qian, N., ... & Min, W. (2019). Spectral tracing of deuterium for imaging glucose metabolism. Nature Biomedical Engineering, 3(5), 402-413.
• Wei, M., Shi, L., Shen, Y., Zhao, Z., Guzman, A., Kaufman, L. J., ... & Min, W. (2019). Volumetric chemical imaging by clearing-enhanced stimulated Raman scattering microscopy. Proceedings of the National Academy of Sciences, 116(14), 6608-6617.
• Shi, L., Liu, X., Shi, L., Stinson, H. T., Rowlette, J., Kahl, L. J., ... & Min, W. (2020). Mid-infrared metabolic imaging with vibrational probes. Nature Methods, 17(8), 844-851.
• Jang, H., Li, Y., Fung, A. A., Bagheri, P., Hoang, K., Skowronska-Krawczyk, D., ... & Shi, L. (2023). Super-resolution SRS microscopy with A-PoD. Nature Methods, 20(3), 448-458.
• Li, Y., Zhang, W., Fung, A. A., & Shi, L. (2022). DO‐SRS imaging of diet-regulated metabolic activities in Drosophila during aging processes. Aging Cell, 21(4), e13586.
• Li, Y., Chang, P., Sankaran, S., Jang, H., Nie, Y., Zeng, A., ... & Shi, L. (2023). Bioorthogonal stimulated Raman scattering imaging uncovers lipid metabolic dynamics in Drosophila brain during aging. GEN biotechnology, 2(3), 247-261.
• Li, Y., Munoz-Mayorga, D., Nie, Y., Kang, N., Tao, Y., Lagerwall, J., ... & Chen, X. (2024). Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK. Cell Metabolism.
• Zhang, W., Li, Y., Fung, A. A., Li, Z., Jang, H., Zha, H., ... & Shi, L. (2024). Multi-molecular hyperspectral PRM-SRS microscopy. Nature Communications, 15(1), 1599.

Selected book chapters

• Villazon, J. I., & Shi, L. (2024). Advances in Biomedical Imaging Modalities for Cancer Research and Diagnostics.
• Wei, W., Wang, X., Li, Y., Cheng, Y., Fung, A. A., Yang, X., & Shi, L. (2021). Advances in optical imaging of drug delivery across the blood-brain barrier. In Progress in Optics (Vol. 66, pp. 171-253). Elsevier.
• Li, Y., & Shi, L. (2022). Isotope-probed SRS (ip-SRS) imaging of metabolic dynamics in living organisms. In Stimulated Raman Scattering Microscopy (pp. 421-443). Elsevier.
• Rodríguez-Contreras, A., Shi, L., & Alfano, R. R. (2022). Effects of tryptophan metabolism on the brain: From early development to Alzheimer's disease. In Biophotonics, Tryptophan and Disease (pp. 107-114). Academic Press.

References

1. "Lingyan Shi - Jacobs School of Engineering".
2. "Super-resolution SRS microscopy with A-PoD".
3. ^ "iCANX Awards".
4. "Fellows Database-Alfred P. Sloan Foundation".
5. "2021 Rising Stars of Light Final Winners" (PDF).
6. ^ "Laser Focus World 2021 Rising Stars Awards: Lingyan Shi".
7. "Announcing the Winners of the 2018 Blavatnik Regional Awards for Young Scientists".
8. "2025 Women in Optics notebook".
9. "Shi Lab".
10. "Principal Investigator - Shi Lab".
11. "Peer-reviewed Journal Publications-Shi Lab".
12. "Compact optical virus detection analyzer of nano- and micro-size bioparticles using light scattering and fluorescence".
13. "System, method and computer-accessible medium for use of heavy water as a probe for imaging metabolic activities".
14. "Resonant stimulated Raman scattering microscope".
15. "Transmission in near-infrared optical windows for deep brain imaging".
16. "Researchers open 'Golden Window' in deep brain imaging".
17. ""Golden Window" in Deep Brain Imaging".
18. "Label-Free Fluorescence Spectroscopy for Detecting Key Biomolecules in Brain Tissue from a Mouse Model of Alzheimer's Disease".
19. "Spectroscopy indicates biomarkers for Alzheimer's disease".
20. "Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK".
21. "Challenging Old Theories: Innovative Microscopy Exposes New Alzheimer's Treatment Pathways".
22. "Innovative Microscopy Demystifies Metabolism of Alzheimer's".
23. "Optical imaging of metabolic dynamics in animals".
24. "Spectral tracing of deuterium for imaging glucose metabolism".
25. "Mid-infrared metabolic imaging with vibrational probes".
26. ^ "DO-SRS imaging of diet-regulated metabolic activities in Drosophila during aging processes".
27. "Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK".
28. "Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK".
29. "Super-resolution SRS microscopy with A-PoD".
30. "Deep imaging in tissue and biomedical materials: using linear and nonlinear optical methods".
31. "Neurophotonics and biomedical spectroscopy".
32. "Hellman Fellowship Recipients".
33. "Fellows Selected for New Scialog: Advancing BioImaging".
34. "Four Early Career Professors at UC San Diego Awarded Sloan Research Fellowships".

• American professors
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• New Jersey Institute of Technology alumni
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• University of California, San Diego faculty
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