Our Research

Modular and efficient reprogramming of the immune system offers a long term solution to a various diseases including cancer, autoimmune disorders, chronic diseases, and beyond. Immunotherapies like checkpoint blockade have already transformed cancer treatment, but their full potential remains untapped. Over 80% of patients either cannot receive or do not respond to current immunotherapies, underscoring the need for innovative strategies to better train and activate the immune system. 

Current challenges in immunotherapy include:

•Limited immune checkpoint targets

•Lack of tumor-associated immune cell selectivity resulting in immune-related adverse events (irAEs)

•Reliance on conventional occupancy-driven mechanisms

Research in the Morimoto lab centers around chemical immunology, where we develop chemical approaches to discover and target new immune-regulating mechanisms. We focus on two key areas: Glycoimmunology - the study of glycans (sugars) exert broad-spectrum control over many immunological processes, and chemically induced proximity - altering protein-protein interactions in immune cells. 

Glycan-Inspired Small Molecule Design 

Glycans represent the next frontier in medicinal chemistry. The shallow binding pockets of lectins (glycan-binding proteins), extreme hydrophilicity/complexity of their native glycan ligands, and multivalent binding modes make the development of potent synthetic binders challenging. As such, previous approaches have often involved high molecular weight polymers and biomaterials that heterogeneously display many equivalents of a simple monosaccharide, posing challenges in both synthetic reproducibility and lectin selectivity. We seek to develop new paradigms for the design of small molecule (low molecular weight) glycomimetic inhibitors and targeting agents, which can be utilized to better harness this critical yet under-explored axis of immune control. 

Discovery of Disease-Specific Glycobiomarkers

We are developing new translational tools to characterize cancer and pre-malignant disease through the lens of glycobiology. A key focus is on endometriosis (EMS), a chronic gynecological condition that currently has no cure and lacks non-surgical diagnostic methods. Stromal and serum samples collected from EMS patients are analyzed using state-of-the-art glycan proteomics (glycoproteomics), in-house high throughput multiplexing assays, and donor-derived macrophage co-culture models to identify clinically relevant glycan markers and immune modulating pathways in EMS. 

Chemically Induced Proximity

Traditional drug development often targets a single protein of interest using small molecule or antibody binders that blocks the active site. Using the principles of chemically induced proximity, we design chimeric small molecules and biologics that modulate specific protein-protein interactions (PPIs) in immune cells to recircuit and restore their healthy function. We are particularly interested in proximity-based strategies that reprogram tumor associated macrophages (TAMs), dysfunctional macrophages that drive immunosuppression within the tumor microenvironment. These chimeric molecules are developed, not only as potential immunotherapies, but to deconvolute the precise molecular mechanisms of fundamental immunological processes such as antigen presentation.