PIPages
Labs

Linda C Hsieh-Wilson

California Institute of Technology, CA·Chemistry

Sugars do much more than supply energy. Long sugar chains coat cells and fill the space between them.

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Fields

Chemistry

Biochemistry

Neuroscience

Topics

glycosaminoglycans

heparan sulfate

chondroitin sulfate

Grants
4 known grants, through Feb 2030

What they work on

  1. Map glycosaminoglycans (GAGs) in the hypothalamus and disrupt them in animal models to test effects on food intake, body weight and blood sugar control.
  2. Define how GAGs bind and organize leptin and GLP-1 hormone-receptor complexes, and test how this changes receptor signaling and the activity of hypothalamic neurons.
  3. Expand libraries of structurally defined heparan sulfate (HS) sugar chains and improve the lab's solution-phase automated synthesis platform to reach new HS sequences.
  4. Determine how growth factors and chemokines read, and sulfotransferase enzymes write, the HS sulfation code, using HS libraries and machine-learning analysis, and target these interactions in lung disease.
  5. Develop molecules that change chondroitin sulfate (CS) sulfation and remodel the brain ECM, and use them to control perineuronal nets that limit brain plasticity.
  6. Test how CS sulfation affects excitatory synapse formation, harmful immune cell states in brain inflammation, and maturation of the cells that remyelinate nerves.
  7. Determine how the O-GlcNAc sugar tag on disordered protein regions alters biomolecular condensates linked to Alzheimer's disease, and how the enzyme OGT is regulated at synapses.
  8. Apply the NISE chemoproteomic method to patient-derived stem cells and human Alzheimer's brain samples to find O-GlcNAc changes during disease.

More about the research

Sugar tags attached to proteins can change what those proteins do. Because these sugars are hard to make and analyze, their biological roles remain poorly understood. The lab uses organic chemistry, chemical tools, mass spectrometry and computation to read the information encoded in sugars. Its projects focus on glycosaminoglycans (GAGs), long chains with sulfate groups placed in specific patterns, in the brain, the lung and metabolism. A further project studies O-GlcNAc, a single-sugar tag on proteins, in neurodegeneration.

Why it matters

This work could reveal new treatment targets for obesity, type 2 diabetes and poor responses to GLP-1 drugs. It could also help with lung diseases such as pulmonary hypertension, acute respiratory distress syndrome and asthma. In the brain, it may point to strategies that restore plasticity, reduce inflammation and promote repair in Alzheimer's disease, related dementias and multiple sclerosis. The new sugar libraries and chemical tools could also help other researchers study sugar biology.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Decoding the Structure-Function Relationships of Glycosaminoglycans in the Lung using Heparan Sulfate Libraries

NIH · Jul 2026 – Feb 2030

NSF-ANR: Unravelling the Critical Role of the Extracellular Matrix in the Functions of the Hypothalamus

NSF · Aug 2026 – Jul 2029

Chemical approaches to understanding chondroitin sulfate glycosaminoglycans and their roles in brain plasticity and pathology

NIH · Jun 2024 – May 2029

Closest labs

Larisa Litovchick

Virginia Commonwealth University, VA·Pharmacology

Test whether high levels of chondroitin-4-sulfate (C4S), a sulfated sugar chain on tumor cells, contribute to platinum resistance in ovarian cancer, using mouse tumor models.

Xiaoyong Yang

Yale University, CT·Physiology

Determine whether O-GlcNAc signaling in ventromedial hypothalamus neurons sets the body weight setpoint, using mice with increased or deleted O-GlcNAc transferase (OGT) and comprehensive physiological measurements of weight and glucose.

Hiroshi Nakato

University of Minnesota, MN·Genetics

Determine how septate junction components, which seal neighboring gut cells together, help end regeneration in the Drosophila midgut after intestinal stem cells repair damage.

The school

California Institute of Technology: 18 labs on PI Pages, $445M a year on research, 200 research doctorates a year.

More about California Institute of Technology

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