We study lymphatic and blood vascular biology, cancer biology, immunoengineering, and regenerative medicine. To address key questions in these fields, we employ 3D organs-on-chip in vitro platforms, molecular biology tools, and in vivo animal models.
1. Mechanisms of lymphedema (LE):
Lymphatic vessels play a role in maintaining fluid homeostasis by draining excess interstitial fluid (IF). A failure in the lymphatic drainage can accumulate IF, causing tissue swelling, which is referred to as “Lymphedema (LE)”. LE is the most common lymphatic disease influencing more than 150 million individuals worldwide. Currently, therapeutic options for LE treatment are limited, as there is no clinically available drug. One of the major obstacles to better understanding and curing the disease is a lack of appropriate experimental models for easily assessing lymphatic drainage in different biological conditions. We aim to understand the mechanism of lymphatic junction remodeling and drainage in LE by employing a microfluidic device (“lymphatics-on-a-chip”) and animal models.
2. Lymphatics in host immunity:
Lymphatics modulate host immunity by interacting with antigen presenting cells like dendritic cells (DCs). The majority of lymphedema (LE) patients suffer from frequent skin infections, known as “cellulitis”, owing to the impaired immunity. Cellulitis results in chronic inflammation and irreversible fibrotic disease progression in LE. Under infection, normal lymphatics rapidly uptake DCs and transport them to draining lymph nodes (dLNs) allowing the dLN-residing T cells activated by the DCs. However, lymphatics in LE are poor at DC trafficking to lymphatics, whose mechanism is not completely understood. We focus on DC interactions to lymphatics in LE to understand LE-associated cellulitis using mouse LE & skin infection models, and 3D on-chip systems.
3. Engineered lymphatic and blood vascular implants:
Blood vascular perfusion is important for implanting large-scale tissue constructs in vivo. Lymphatic drainage is another key factor in tissue fluid homeostasis. We hypothesize that adding lymphatics to the pre-vascularized patch can improve tissue function by providing both blood vascular perfusion and lymphatic drainage. We test this novel hypothesis utilizing perfusable, pre-vascularized 3D lymphatic patch.
4. Tumor interactions to the blood and lymphatic vasculature:
Lymphatics and blood vessels are major routes of tumor dissemination. Though we acknowledge some cytokines as metastatic chemical signals, tumor interactions to these vasculatures are largely unknown under certain tumor microenvironmental conditions, such as hypoxia, stiff ECM, under chemotherapies, etc. We develop 3D tumor-on-a-chip and various mouse tumor growth and metastasis models to solve the questions.