醣化作用（glycosylation）是細胞重要的後轉譯修飾。細胞表面醣分子可透過與醣受體及其他配體互動，調控細胞訊息傳遞、增生、分化、癌化、免疫辨識與免疫監控。腫瘤與白血病細胞常出現腫瘤相關醣類抗原（tumor-associated carbohydrate antigens, TACAs）及異常唾液酸化（hypersialylation），並可能藉由結合免疫細胞上的唾液酸結合免疫球蛋白樣凝集素（sialic acid-binding immunoglobulin-like lectins, Siglecs），削弱免疫細胞的辨識與效應功能，形成免疫逃脫。

本研究團隊以 Siglec-7 為核心，探討細胞表面醣結構、免疫受體訊號、粒線體功能與細胞代謝之間的交互作用，研究主軸包括：

1. 細胞表面醣修飾與自然殺手細胞免疫監控
   探討腫瘤及白血病細胞的醣鏈、唾液酸化與 Siglec-7 配體如何影響自然殺手細胞（natural killer cells, NK cells）的辨識、去顆粒、細胞毒性及細胞激素分泌。
2. Siglec-7 調控 NK 細胞粒線體與代謝
   研究 Siglec-7 如何連結粒線體分裂與融合、氧化磷酸化、能量代謝及代謝重編程，進而限制人類 NK 細胞的細胞毒性功能。
3. Siglec-7 與巨核細胞生成及血小板生成
   探討 Siglec-7 在巨核細胞生成（megakaryopoiesis）與血小板生成（thrombopoiesis）中的表現、功能及其與粒線體動力學的關聯，解析其在巨核細胞分化、血小板生成及血小板功能中的生理作用。
4. 造血細胞分化與血液腫瘤
   以紅血球生成、巨核細胞分化、白血病細胞及 NK 細胞為研究模型，解析醣鏈修飾、轉錄與表觀遺傳調控、粒線體代謝及免疫效應之間的分子機制。
5. 醣類標誌與轉譯應用
   發展可用於評估免疫細胞功能、腫瘤免疫逃脫、血液疾病及血小板生物學的醣類與 Siglec-7 相關分子標誌，並探索其在疾病分層、預後評估及免疫治療策略中的應用潛力。

整體研究方向聚焦於「醣化作用—Siglec-7—粒線體—免疫與造血功能」之整合性機制，期望闡明細胞表面醣訊號如何轉化為粒線體與代謝反應，進而調控免疫細胞效應及造血細胞分化。

Research Interests

Glycosylation is an important post-translational modification that regulates a wide range of cellular processes. Cell-surface glycans interact with glycan-binding receptors and other ligands to modulate intracellular signaling, cell proliferation, differentiation, oncogenic transformation, immune recognition, and immune surveillance. Tumor and leukemia cells frequently exhibit tumor-associated carbohydrate antigens (TACAs) and aberrant hypersialylation. Through interactions with sialic acid-binding immunoglobulin-like lectins (Siglecs) expressed on immune cells, these altered glycan structures may attenuate immune recognition and effector functions, thereby contributing to immune evasion.

Our research focuses on Siglec-7 and investigates the interplay among cell-surface glycan structures, immune-receptor signaling, mitochondrial function, and cellular metabolism. Major research areas include:

1. Cell-surface glycosylation and natural killer cell immune surveillance
   We investigate how glycan structures, sialylation, and Siglec-7 ligands on tumor and leukemia cells regulate natural killer (NK) cell recognition, degranulation, cytotoxicity, and cytokine production.
2. Siglec-7 regulation of mitochondrial function and metabolism in NK cells
   We study how Siglec-7 connects mitochondrial fission and fusion, oxidative phosphorylation, energy metabolism, and metabolic reprogramming to restrain the cytotoxic function of human NK cells.
3. Siglec-7 in megakaryopoiesis and thrombopoiesis
   We investigate the expression and function of Siglec-7 during megakaryopoiesis and thrombopoiesis, with particular emphasis on its relationship with mitochondrial dynamics and its physiological roles in megakaryocytic differentiation, platelet production, and platelet function.
4. Hematopoietic differentiation and hematological malignancies
   Using models of erythropoiesis, megakaryocytic differentiation, leukemia, and NK-cell biology, we examine the molecular mechanisms linking glycan remodeling, transcriptional and epigenetic regulation, mitochondrial metabolism, and immune effector functions.
5. Glycan-related biomarkers and translational applications
   We aim to identify glycan- and Siglec-7-related molecular biomarkers for evaluating immune-cell function, tumor immune evasion, hematological disorders, and platelet biology, and to explore their potential applications in disease stratification, prognostic assessment, and immunotherapeutic development.

Overall, our research centers on the integrated glycan–Siglec-7–mitochondria–immune and hematopoietic function axis. We seek to clarify how cell-surface glycan signals are translated into mitochondrial and metabolic responses that regulate immune-cell effector functions and hematopoietic-cell differentiation.