Dana-Farber Cancer Institute · Broad Institute of MIT and Harvard
Decoding and rewiring the cell surface for immune therapy
We study how cell surface glycan and protein interactions control immune recognition, with the goal of engineering the cell surface for better cell and immune therapies.
Biology at the interface
Despite being highly targetable, the cell surface is undermapped
The cell surface is a dynamic interaction hub governing intercellular communication, immune recognition, and pathogen entry. It is the site of action of more than half of approved drugs, including cancer immunotherapy, engineered cell therapy, and antibody-drug conjugates.
Yet we have a limited understanding of the structure, organization, and regulation of the key biomolecules in this compartment. Beyond the roughly 3,000 cell surface proteins, every cell is coated with sugars, or glycans. Glycans form a dense, lattice-like canopy that shields membrane receptors, organizes protein neighborhoods, and modulates immune activation.
Because glycans are not template-encoded and have historically been hard to measure, this layer of the cell surface has been poorly mapped and understood.
We map and decode the function of the glycans that coat the cell surface by combining complementary technologies in functional genomics, proteomics, and immunology. These studies teach us how glycans remodel the cell surface, shape intercellular signaling, and organize the immune synapse, with insights translating into the next generation of cell and immune therapies.
Where we started
A glycan shield hides leukemia from the immune system
Our recent work, using functional genomics and glycoengineering, demonstrates a key role for glycans in mediating immune evasion in acute myeloid leukemia.
We found that in leukemia cell surface O-glycosylation and sialylation, particularly of the glycoprotein CD43, is potently inhibits macrophage phagocytosis and NK- and T-cell cytotoxicity, by forming a steric shield that physically restrains immune interactions.
We are hiring
We seek highly motivated and creative post-docs, students, and computational biologists.