Tumor molecular immunology
Research Field
Dr. Yi-Ching Wang received her PhD in Genetics from Michigan State University, USA, in 1993. She returned to Taiwan to join the Institute of Biomedical Sciences at Academia Sinica for post-doctoral training. Dr. Wang became an associate professor at the Institute of Toxicology at Chung Shan Medical University in 1995. She then joined the Department of Life Science at National Taiwan Normal University and was promoted to professor in 1999. In 2006, Dr. Wang moved to the Department of Pharmacology, College of Medicine, National Cheng Kung University, where she served as Distinguished Professor until 2015, when she took up the current position as Chair Professor at the same university.
As a Principal Investigator for the last 31 years, Dr. Wang has published 147 SCI papers in journals such as Nature Communications, Science Advances, Journal of Clinical Investigation, Nucleic Acids Research, Cell Death & Differentiation, Cancer Research, Clinical Cancer Research, Theranostics, with an H-index of 52. In addition, her group has reported 427 conference papers, 4 book chapters, and obtained 4 Taiwan patents, 2 US patents, and 2 PCT patents.
Dr. Yi-Ching Wang has a longstanding research interest in unraveling the molecular mechanisms underlying tumorigenesis. Dr. Wang specifically investigates the relationship between alterations in tumor suppressor genes, oncogenes, and cancer signaling. Recently, Dr. Wang’s attention has shifted towards studying post-translational modifications of the inhibitory receptors on T cells and their therapeutic strategies. Dr. Wang’s laboratory is also involved in the development of several potential anti-cancer drugs and immunomodulation antibodies. These ongoing projects aim to translate the scientific findings into practical applications that benefit cancer patients.
Dr. Yi-Ching Wang investigates the molecular mechanisms underlying lung, esophageal, pancreatic, and colorectal cancers. Her recent work focuses on post-translational modifications of immune checkpoint molecules, stromal-cancer crosstalk, and the role of the small GTPase Rab37 in immune modulation of the tumor microenvironment and cancer progression. Her group also studies cancer-related transcription factors, including NF-κB, STAT3, Oct4, ZNF322A, and SOX17, as well as cytokines and secretory factors such as IL-2, IL-6, IL-33, CCL2, and chitinase-3-like protein 1. In parallel, her team is developing novel anticancer small-molecule therapeutics, immunomodulatory antibodies, and cytokines.
Dr. Wang’s team investigates the role of NRF2, an antioxidant transcription factor, in cancer progression and drug resistance. In parallel, her laboratory studies the function of the small GTPase Rab37 in exocytosis, the consequences of Rab37 dysregulation in tumorigenesis, and its impact on the tumor microenvironment. More recently, Dr. Wang’s research has expanded to post-translational modifications of inhibitory receptors on immune cells and their roles in immune modulation during tumorigenesis. The stromal–cancer crosstalk that shapes the tumor microenvironment and drives cancer progression is also a major focus of her laboratory. In addition, her group investigates cancer-related transcription factors, including NF-κB, STAT3, Oct4, ZNF322A, and SOX17, as well as cytokines and secretory factors such as IL-2, IL-6, IL-33, CCL2, and chitinase-3-like protein 1.
Beyond fundamental research, Dr. Wang’s laboratory is actively engaged in the development of novel anticancer small-molecule therapeutics, immunomodulatory antibodies, and cytokines. These ongoing efforts aim to translate fundamental scientific discoveries into clinically applicable strategies that ultimately benefit cancer patients.
Dr. Wang's major research fields are listed below.
- Post-translational modifications of immune checkpoints
- Vesicle trafficking and tumor microenvironment
- Stromal-cancer cross-talk in the tumor microenvironment
- Transcription deregulation in cancer
- Cancer signaling
- Anticancer drug/antibody development
- Translational medicine
2025, The 2025 Excellent Research Award of National Cheng Kung University 成大114年卓越學術研究獎
2024, NSTC Appointed Outstanding Research Award 國科會傑出特約研究員獎
2023, Tien Te Lee Biomedical Foundation for Excellent Biomedical Award, Taiwan 永信李天德醫藥基金會「卓越醫藥科技獎」
2022, The Ministry of Education’s 66th Annual Academic Award, Taiwan 第66屆教育部學術獎
2021, The Foundation for the Advancement of Outstanding Scholarship Award, Taiwan 傑出人才發展基金會 傑出人才講座
2018, K. T. Li Honorary Scholar Award, Taiwan 李國鼎科技與人文講座 榮譽學者獎
2017, Dr. Wang Min-Ning Memory Foundation for Excellent Basic Medical Research award, Taiwan 財團法人王民寧先生紀念基金會基礎醫學類 傑出貢獻獎
2017, Excellent paper award, Taiwan Cancer Medicine Journal, Taiwan 台灣癌症醫學雜誌第三屆優良論文獎
2015~Now, Chair Professor, College of Medicine, National Cheng Kung University, Taiwan 國立成功大學講座教授
2014, 2010, 2004, Outstanding research award of the National Science Council / Ministry of Science and Technology, Taiwan 國科會/科技部傑出研究獎（共三次）
2013, Dr. Tung Ta-Cheng Memorial Award for Basic Cancer Research, Chinese Oncology Society, Taiwan中華民國癌症醫學會董大成博士癌症基礎醫學研究傑出獎
2010, Outstanding research award, College of Medicine, National Cheng Kung University, Taiwan 成大醫學院最佳論文獎
2008~2026, Research award of Cheng-Shin Medical Foundation, Taiwan成杏基金會優秀論文獎
2008, Outstanding research award, Pharmacology Society, Taiwan 藥理學會傑出研究獎
2007, Distinguished alumnus of Chinese Culture University, Taiwan 中國文化大學傑出校友
Education
1983~1987 BS, Horticulture, Chinese Culture University, Taiwan
1988~1993 PhD, Genetics, Michigan State University, USA
Positions and Employment
1993~1995 Post-doctoral fellow, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
1995~1999 Associate Professor, Institute of Toxicology, Chung Shan Medical Univ., Taichung, Taiwan
1999~2006 Professor, Department of Life Science, National Taiwan Normal Univ., Taipei, Taiwan
2006~2015 Distinguished Professor, College of Medicine, National Cheng Kung University, Tainan, Taiwan
2015~now Chair Professor, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Job Description
The work items are described below.
Develop and validate next-generation IL-2-based fusion biologics that preferentially expand cytotoxic CD8⁺ T cells while minimizing Treg amplification and further overcome tumor-stroma-immune barriers to improve immunotherapy outcomes in lung and pancreatic cancer.
Specific aims
- To determine the anti-tumor efficacy and immune-reprogramming mechanism of IL-2 variant (CCL) and CCL-based bi-/tri-fusion biologics, and AI translational IL-2 in NSCLC and PDAC models.
- To evaluate the dual anti-tumor and anti-fibrosis therapeutic potential of IL-2 variant (CCL) and CCL-based bi-/tri-fusion biologics, and AI translational IL-2 in NSCLC and PDAC models.
- To establish an ex vivo platform to test the PBMCs and tumor slides derived from ICB non-responder and reverse exhaustion signatures with IL-2 variant (CCL) and CCL-based bi-/tri-fusion biologics with effective biomarkers.
We propose (Aim 1) a next-generation IL-2 platform centered on an IL-2 variant (CCL) engineered to minimize IL-2Rα binding while preserving IL-2Rβ/γ engagement, thereby preferentially potentiating cytotoxic CD8⁺ T cells over Tregs. Building on this, we will develop CCL-based fusion biologics by incorporating a disintegrin domain to disrupt tumor-ECM/stroma interactions and further integrate checkpoint blockade through antibody fusion to maximize anti-tumor efficacy and overcome adaptive resistance. To validate the therapeutic breadth of these biologics, Project 2 will systematically investigate (Aim 2) the dual anti-tumor and anti-fibrotic potential of these CCL and CCL-based bi-/tri-fusion biologics in NSCLC and PDAC models, accounting for the distinct immunosuppressive landscapes of these malignancies. Furthermore, we will establish (Aim 3) an ex vivo platform to longitudinally monitor immune responses in PBMCs derived from NSCLC patients undergoing ICB, evaluating circulating IL-2 dynamics and functional T-cell reinvigoration as predictive biomarkers for IL-2-based immunomodulation.
Expected results
Expected Work Items:
- Establish both subcutaneous and orthotopic LLC (NSCLC) and KPC (PDAC) murine models for evaluating the anti-tumor and anti-fibrotic efficacy of CCL and bi-specific CCL-Disintegrin fusion proteins.
- Perform flow cytometry to verify IL-2Rβ/γ-biased signaling and initial TME reprogramming.
- Characterize the impact of α5β1-targeting on the desmoplastic stroma of NSCLC and PDAC models.
- Patient Enrollment: Start collecting the PBMCs and tumor slides from ICB patients.
Expected Training for Personnel:
- Surgical Proficiency: Mastery of orthotopic implantation (lung and pancreas) in murine models.
- Immune Profiling: Training in flow cytometry for TIL analysis (CD8+ and Treg).
Expected Research Results:
- Evidence that CCL significantly induces Ki-67, IFN-γ, TNF-α, and Granzyme B in effector CD8+ T cells, while maintaining minimal expansion of Tregs (CD4+CD25+Foxp3+).
- Preliminary data demonstrate that CCL has a superior safety profile compared with wild-type IL-2 (C125S).
- Confirmation of the Disintegrin module's ability to reduce α-SMA+ fibroblasts and enhance CD8+ T-cells in murine models
Preferred Intern Educational Level
A student with a BS or MS degree is eligible to conduct this project.
PhD students are also very welcome.
Skill sets or Qualities
Expected Training for Personnel:
- Surgical Proficiency: Mastery of orthotopic implantation (lung and pancreas) in murine models.
- Immune Profiling: Training in flow cytometry for TIL analysis (CD8+ and Treg).
- Training in advanced IHC and IF-IHC with quantitative spatial image analysis.
- Functional Assays: Mastery of flow-based tumor killing assays and E:T ratio optimization.
- Clinical Coordination: Training in IRB compliance, patient recruitment, and standardized PBMC isolation/cryopreservation.