專長
腫瘤組織微環境、腫瘤免疫學、腫瘤間質治療學
EXPERTISE
Tumor Microenvironment, Oncoimmunology, Stroma-Targeting Therapeutics
研究興趣
腫瘤組織不只由增生的表皮型細胞所組成，更含有大量如纖維母細胞及巨噬細胞等具增生能力的間質細胞。許多惡性腫瘤具有組織間質增生的特徵，而呈現出腫瘤快速生長、免疫逃脫、發生轉移及抗藥性之嚴重性，因此黃博士的研究團隊長年聚焦於腫瘤形成及惡化時組織微環境改變的研究，建立了多種基因轉殖及混合細胞接種之實驗鼠模型，探討腫瘤組織中不同種細胞間的交互作用及其影響，另外，黃博士實驗室及其合作團隊亦致力於針對腫瘤組織間質增生的藥劑與策略之研發，以期對惡性腫瘤的治療有所助益。
RESEARCH INTERESTS
Solid tumor tissue is not only composed of neoplastic epithelial cells, rather, it comprises a range of proliferating stromal cells such as fibroblasts and macrophages. Dr. Huang’s research team has been focusing on the tissue microenvironment reprogramming for cancer development and progression. They have exploited several transgenic and mixed cells-transplanted mouse models to explore the cell-cell interplays in the desmoplastic tumor microenvironment. Desmoplasia is a common hallmark of many malignancies including non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, and pancreatic ductal adenocarcinoma (PDAC). In a PDAC tissue, desmoplastic stroma generally constitutes 70~90% of total tumor volume and is closely associated with rapid tumor growth, immunosuppression, metastasis, and therapeutic resistance. Dr. Huang’s laboratory is also paying much attention on the therapeutics targeting desmoplastic PDAC stroma.
研究發展介紹
“從癌組織的不正常基質細胞尋找對付胰臟癌的新治療策略”
國衛院電子報 第889期 (https://enews.nhri.org.tw/research/5525/)
“骨髓衍生的巨噬細胞及相關的分泌性熱休克蛋白90α是胰管腺癌形成的早期致病因子”
國衛院電子報 第754期 (https://enews.nhri.org.tw/research/447/)
RESEARCH ACTIVITIES & ACCOMPLISHMENT
Cancer desmoplasia results from the production of a huge amount of extracellular matrix by a remarkable number of myofibroblasts. Myofibroblasts, also known as activated fibroblasts or cancer-associated fibroblasts (CAFs), can be derived from activation of stellate cells or tissue-resident fibroblasts. Additionally, 30~40% of CAFs can arise from the endothelial-to-mesenchymal transition (EndoMT) of endothelial cells. In Dr. Huang’s recently published results, EndoMT-derived CAFs can exhibit a potent tumor-promoting effect by producing extracellular HSP90α (eHSP90α) to foster gaining-of-stemness of colorectal cancer cells. Additionally, a mix of EndoMT-derived CAFs with PDAC cell grafts significantly recruits myeloid-derived macrophages, prevents immune T cells, and promotes the growth of tumor with desmoplasia. EndoMT-derived CAFs can facilitate M2-polarization of tumor-infiltrating macrophages through CD91-TLR4 receptor and MyD88-IRAK complex-associated IKKα/β−NF-κB/IRF3 and JAK2/TYK2−STAT-3 signaling pathways. The M2-polarized macrophages do not only secrete IL-10 and TGF-β to suppress effective and cytotoxic T cells, but also produce VEGF to stimulate tumor angiogenesis. Moreover, these M2-polarized macrophages express and secrete a great amount of eHSP90α and create an eHSP90α-rich tumor microenvironment which has the advantage of cancer cell spreading and gain-of-stemness. In collaborating with the research teams at Institute of Biotechnology and Pharmaceutical Research, Dr. Huang and his colleagues have been developing novel anti-desmoplasia agents and strategies for pancreatic adenocarcinoma therapy.
