We focus on lymphatics to improve our knowledge of cancer biology, immuno-engineering, and regenerative medicine. Four major topics are described below. In each topic, we employ 3D organs-on-chip in vitro platforms, molecular biology tools, and in vivo animal models.
1. Lymphatics for maintaining tissue fluid homeostasis:
Lymphatic vessels play a role in maintaining fluid homeostasis by draining excess interstitial fluid. A failure in lymphatic drainage abnormally accumulates interstitial fluid, causing tissue swelling (“lymphedema”). Though lymphedema is the most common lymphatic disease influencing more than 150 million individuals worldwide, therapeutic options for lymphedema treatment are limited and there is no clinically available drug. We aim to understand the mechanisms of lymphatic junction morphogenesis, sprouting, valve formation, mural cell interactions, and fluid transport in lymphedema by employing microfluidic devices and animal models.
2. Organ-specific lymphatic function and disease:
Lymphatics exist not only under the skin but in every organ, such as the small intestine, joints, eyes, and brain. We model organ-specific lymphatics on-chip and investigate lymphatic function in organ-specific diseases. We develop in vitro and in vivo models to validate our findings in each context of different organs.
3. Lymphatics in immunity, inflammation, and cancer immunotherapy:
Lymph fluid contains immune cells and antigens, so lymphatics carrying lymph fluid modulate host adaptive immunity. We focus on functional and structural changes in lymphatics in inflammation, autoimmune disease, and cancer and investigate immune cell interactions with lymphatics to develop new immunotherapies for treating chronic immune diseases and cancer.
4. Tumor spreading through lymphatics and blood vessels:
90% cancer deaths come from metastasis or tumor spreading. Lymphatics and blood vessels are major routes of tumor dissemination given tumors form new lymphatic and blood vessels in and around the tumors. Tumor cell interactions with those vasculatures are not completely understood. We develop 3D tumor-on-a-chip for various tumor types and employ physiologically relevant mouse tumor models to address the questions.
Funding
NIH R01 CA279560 (PI: Lee) 2023 – 2028
NIH R01 HL165135 (PI: Lee) 2022 – 2027
NIH R21 AI168886 (PI: Lee) 2023 – 2025 (MPI: Deok-Ho Kim)
NIH R21 CA252162 (PI: Lee) 2022 – 2024
NIH R21 AI166772 (PI: Lee) 2021 – 2023