Forschung

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are essential components of immune surveillance, responsible for eliminating tumor cells and pathogen-infected cells. To fulfill this role, these immune killer cells must navigate complex three-dimensional (3D) environments in vivo to locate and destroy their target cells. However, tumor heterogeneity remains a significant obstacle in oncology. Antigen variability between patients—and even within individual tumors—permits subsets of tumor cells to evade immune surveillance, leading to recurrence and treatment resistance.

In contrast, physical cues within the tumor microenvironment, such as stiffness, confinement, and interfacial topology, undergo consistent and predictable ways during tumor progression. Intriguingly, similar changes in physical cues are also observed in the context of infection. Recent studies, including our own, highlight the promising potential of targeting these pathologically altered physical cues to modulate immune responses in a controlled and therapeutically beneficial manner.

My lab aims to systematically investigate how physical and mechanical cues regulate the behavior and function of CTLs and NK cells, with a particular focus on diseases marked by altered tissue mechanics—such as solid tumors and obesity, aiming to translate these insights into strategies for more precise and effective therapies.

Key Research Directions

1. Biophysical Regulation of Immune Surveillance

2. Enhancing Cytotoxicity via Smart Biomaterials

3. Organ-Specific 3D Platforms for Drug Screening

Methodology

We leverage multidisciplinary techniques, including:

• High-throughput in vitro 3D extracellular matrix models to mimic in vivo environments.
• Live-cell imaging with fluorescent probes to monitor cytoskeleton dynamics, calcium influx, metabolic changes, and protein trafficking.
• Functional assays to measure immune synapse formation, cytokine release, and cytotoxic granule transport.
• Systems biology approaches, such as multi-omics and mathematical modeling, to uncover mechanistic insights.