Weiping Tang
University of Wisconsin-Madison, WI·Chemistry
Many disease-causing proteins sit outside cells or on their surface, where common drug strategies cannot reach them. One way around this is to build two-ended molecules: one end grabs the unwanted protein, and the other hooks it onto a receptor that drags it into the cell's lysosome, its recycling compartment, where it is broken down.
- Fields
Chemistry
Pharmacology
Biochemistry
- Topics
targeted protein degradation
lysosome targeting chimera
folate receptor
- Grants
- 2 known grants, through Mar 2029
What they work on
- Synthesize conjugates that link folate, a ligand for the cancer-overexpressed folate receptor, to antibodies against PD-L1, and test how well they degrade PD-L1 in cancer cells.
- Evaluate PD-L1 degradation and anti-tumor efficacy of folate-antibody conjugates in syngeneic and humanized mouse models, focusing on head and neck cancer.
- Study how folate receptor-mediated uptake leads to lysosomal degradation of PD-L1, and why this degradation improves anti-tumor responses.
- Develop predictable methods to acylate, alkylate, or sulfate a single chosen hydroxyl group on minimally protected or unprotected sugars, and to remove protecting groups at chosen sites, using transition metal catalysts and chiral organocatalysts.
- Use site-selectively installed directing groups to form specific glycosidic linkages with control over stereochemistry, and build carbohydrate ligands for lysosome targeting receptors to degrade extracellular disease proteins.
More about the research
This approach builds on carbohydrate chemistry, because many of these receptors recognize specific sugars. Making those sugars in the lab is itself a hard chemistry problem. The research pairs new methods for building carbohydrates with the design of these protein-destroying molecules, including degraders aimed at cancer.
Why it matters
Cancer patients, especially those with head and neck cancer, could benefit if folate-antibody conjugates prove able to remove PD-L1 from tumors and strengthen immune attack. A general platform for tissue-selective degraders could speed drug development against other cancer-linked surface proteins. Faster, more selective ways to make carbohydrates could help chemists prepare bioactive compounds for studying disease and developing therapeutics.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jin Xie
University of Georgia, GA·Biomedical Engineering
Test whether anti-CD205 antibody-conjugated calcium nanoparticles (αCaNPs) selectively raise cytosolic calcium in circulating cDC1 dendritic cells and increase their infiltration into tumors in murine head and neck cancer models.
Jun Wang
New York University, NY·Microbiology & Immunology
Determine whether Siglec-15, a tumor-associated immune brake, also suppresses myeloid cells such as macrophages, and identify the receptors it binds on myeloid cells and T cells.
Qiaobing Xu
Tufts University, MA·Biomedical Engineering
Covalently attach a ligand that binds the target protein onto an E3 ligase-related protein, creating a two-part degrader that avoids the PROTAC hook effect.
The school
University of Wisconsin-Madison: 91 labs on PI Pages, $1.9B a year on research, 854 research doctorates a year.
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