Lingyan Shi, Ph.D.
Shu Chien-Gene Lay Department of Bioengineering
University of California, San Diego
Seminar Information
Every living thing runs on metabolism — the constant chemical activity that builds, powers, and repairs our cells. When that activity goes off course, the result can be aging or disease. Yet it is extremely difficult to watch the dynamics of metabolism happening inside living tissues. Most methods cannot show us where the reactions take place, cannot work in living cells, or cannot follow more than one thing at a time.
My lab has built a novel microscope to solve these problems. It combines several advanced imaging techniques into a single platform that we call multimodal metabolic nanoscopy. The idea is simple at heart: we feed cells harmless, “tagged” versions of everyday nutrients — water, carbohydrates, amino acids, and fats — that carry a subtle chemical marker. As the cells use those nutrients to construct brand-new molecules, our microscope can literally watch the new material appear, at a scale finer than a single cell, without harming the living tissue.
This allows us to see the dynamics if biology as it happens. For example, we have found that in developing, aging, and Alzheimer’s-affected brains, certain stresses cause the support cells in the brain to pile up abnormal fat droplets. By the simultaneous tagging of several nutrients at once, we can also map how different building programs work together and trace the amino-acid pathways right where they occur in cancer models, fruit-fly tissues, human kidney, lung, lymph node, and fallopian-tube, aged human neurons, and mouse livers. In each case, we can reveal how specific cell types rewire their chemistry. Together, these tools offer a precise, non-invasive way to discover how the dynamics of metabolism drive health, aging, and disease, and to uncover new biomarkers that could provide new ways to guide diagnosis and treatment.
Lingyan Shi is a tenured Associate Professor of Bioengineering at UC San Diego, where her lab invents new microscopes that reveal the chemistry of life inside living tissue. She discovered the “Golden Window” (1550–1870 nm) — a band of light that can see unusually deep into tissue. She then pioneered DO-SRS, an imaging method that uses tagged water and nutrients to watch cells build brand-new molecules in real time, and developed a family of techniques (A-PoD, PRM, and SuMMIT-SRS) that push this imaging technique to super-resolution and let it track many molecules at once.
These tools can spot newly made lipids, proteins, DNA and RNA, carbohydrates, and other metabolites inside cells — even telling brand-new molecules apart from older ones, and revealing how metabolism differs from one cell type or organ to the next. Her team has used them to make discoveries with direct medical relevance: showing, for instance, that a protein linked to Alzheimer’s disrupts fat processing in the aging brain by driving support cells to overproduce fat droplets — an effect they were able to reverse. With SuMMIT-SRS, they have mapped how individual cell types rewire their metabolism across breast cancer models, fruit-fly tissue, aged human neurons, and mouse liver, establishing this imaging as a quantitative, non-invasive way to find biomarkers for development, aging, and drug response.
Dr. Shi holds 10 awarded and 18 pending patents. Her honors include the Blavatnik Regional Award for Young Scientists (2018), the Hellman Fellowship (2021), Scialog Fellowships in Advancing Bioimaging from RCSA and the Chan Zuckerberg Initiative (2021–2023), and the Sloan Research Fellowship in Chemistry (2023). She received the Cellular and Molecular Bioengineering Rising Star Award (2024), the IUPS Young Faculty Award (2024), and the Emerging Leader in Molecular Spectroscopy Award (2025), and was elected to the National Academy of Inventors in 2025.