研究特色

Chao Lien Liu, Ph.D

Immunology＆ Immunotherapy, Cell therapy, Immunomodulation, Immunosenescence, aging and age-related diseases

Academic Title:

Associate Professor,

School of Medical Laboratory Science and Biotechnology,

Taipei Medical University, Taiwan.

RESEARCH SUMMARY

Cellular therapy strategies (e.g., CAR-T cells, gamma/delta (gd)-T cells, CAR-NK cells) targeting diseases, including pancreatic adenocarcinoma (PDAC), ovarian cancer (OC), prostate cancer (PC), liver fibrosis, and age-related disorders (e.g., cardiovascular disease and metabolic disease) to assess their immunotherapeutic efficacies and molecular mechanisms.

CLINICAL INTERESTS

1. Cellular therapies including gamma/delta (gd)-T cells, CAR-T cells, Regulatory T cells, CAR-NK cells toward pancreatic adenocarcinoma (PDAC), ovarian cancers (OCs), prostate cancer (PC), and liver fibrosis treatment.
2. Immunomodulation of Aging immunity and treating aged-associated diseases (e.g., cardiovascular and metabolic diseases).

RESEARCH DESCRIPTION

Our long-term goal is to understand the molecular mechanisms of cell-cell interactions during engineered or non-engineered immune cell cytotoxicity toward different diseases and the potential for clinical translational applications. Our laboratory aims to development of immunotherapy strategies/protocols for treating different significant disorders, including solid tumors, liver fibrosis, and age-related diseases. In addition, using the tumor-xenograft humanized mouse models, we want to uncover the molecular mechanisms of immunotherapy and the in-vivo therapeutic immune responses. Several prominent immunotherapy systems have been investigated, including gamma/delta (gd) T cells, chimeric antigen receptor (CAR) T cells, CAR-NK cells, and regulatory T cells.

1. Ex-vivo expanded  gd-T cells and NK cells for treating different diseases

(I). We study the molecular mechanisms of gamma/delta T cells’ cytotoxicity activities toward ovarian cancer. We have demonstrated that ex-vivo expanded gamma/delta T cells from human PBMCs showed potent cytotoxicity towards epithelial ovarian malignancy both in-vitro and in the tumor xenograft mice. Ex-vivo expanded NK cells will be assessed to target aging and aged-associated disorders.

(II). To develop the best clinically feasible therapeutic method, we recently continue to optimize and modify different chimeric gamma/delta-T cells and CAR-NK cells as well as their derived exosomes to target various types of cancers (ex, PDAC, and PC) to achieve the most significant enhancement in therapies. Also, the effects of CAR--T and CAR-NK cells and their derived exosomes for liver fibrosis and aged-associated disorders targeting will be assessed.

2. Engineering chimeric antigen receptor (CAR) T-cells and CAR-NK cells for treating solid tumors and the targeted mechanism assessment in the tumor microenvironment (TME) 

(I). T cells engineered with chimeric antigen receptors (CARs) have been successfully applied in treating patients with malignancies. Our laboratory is using several CAR approaches to combat different solid tumors (e.g., OC, PDAC, and PC). Immune checkpoint inhibitor PD1/PD-L1 pathway plays an essential role in immune suppression in the TME and blockade of PD1/PD-L1 has been successful in treating several tumor types. Besides, Protease Activated Receptor-1 (PAR-1) showed abundant expression in the PDAC-TME as the ideal target antigen. We have developed CAR strategies targeting PD1/PD-L1 and PAR-1/MMP1 pathways for further immunotherapy investigation. More antigenic targets will be assessed further. The goal is to eliminate tumor cells and build potent immunotherapy protocols for clinical translation.

(II). Except for the therapeutic efficacies, immune responses and molecular mechanisms in the TME following CAR-T cell therapy will also be investigated. Accordingly, tumor sphere cell induction ( combined with stroma components (e.g., cancer-associated fibroblast and immune cells) in a 3- 3-dimensional (D) TME model is taken for assessment. Besides, the genetic regulation by small molecules (e.g., miRNA and ncRNA) after TME immunotherapy is under-investigated. 

RESEARCH FOCUS AREA

Ovarian cancers, Pancreatic adenocarcinoma, Prostate cancers, Liver fibrosis, Immunotherapy, Cellular therapies (e.g., gd-T cells, CAR-T cells, CAR-NK cells), Immunomodulation, Aging immunity, Aging-related diseases (e.g., cardiovascular disease, and metabolic diseases)

CONTACT US

Chao Lien Liu, Ph.D.

Mail Stop: NO. 301, Yuantong Road, Zhonghe Dist., New Taipei City 235, Taiwan

TEL: +886-2-6620-2589  ext: 11008

E-mail: chaolien@tmu.edu.tw