基本信息
浏览量:1
职业迁徙
个人简介
Research Interests
Molecular mechanisms of exocytic trafficking, tumor invasion, and immune suppression
1. Molecular basis of exocytosis: Exocytosis is a basic cell biological process mediated by transport, docking, and fusion of secretory vesicles carrying proteins and lipids to the plasma membrane. Through exocytosis, hormones and neurotransmitters can be released. Also, through exocytosis, membrane proteins and lipids can be incorporated into specific domains of plasma membrane for cell surface expansion, cell growth, morphogenesis, and cell migration. Our research aims to address three fundamental questions in cell biology: (1) what is the molecular basis for exocytosis; (2) how do the secretory machinery functions in concert with cytoskeleton and small-GTP-binding proteins during cell polarization and cell migration; (3) how the basic cell biological processes mentioned above are implicated in diseases such as cancer and diabetes. One of our research interests is the evolutionarily conserved multi-protein complex, named the exocyst. The exocyst consists of eight components: Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84, and plays essential roles in secretory vesicle targeting and docking at the plasma membrane during exocytosis. The exocyst is specifically localized to sites of active exocytosis and polarized cell growth, and is a downstream effector of many small GTPases including Rab, Rho, and Ral. In addition, the exocyst is a direct target of many kinases in the cell. Under the control of these signaling proteins, the exocyst coordinates with actin cytoskeleton in many pathophysiological processes such as cytokinesis, ciliogenesis, cell migration, and tumor invasion.
2. Exosomes in cancer: We are studying the molecular mechanisms that regulate the biogenesis and secretion of exosomes, which are lipid-encapsulated small vesicles secreted by a wide variety of cells. Furthermore, we aim to understanding how cancer cell-derived exosomes and other types of extracellular vesicles influence tumor microenvironment to effectively promote tumor growth, metastasis and immune evasion. We recently found that tumor-derived exosomes carry the immune checkpoint protein PD-L1, and systemically suppress the immune system. We are currently investigating how oncogenic signals regulate the biogenesis of PD-L1 exosomes and how manipulating exosome trafficking could improve the response of cancer patients to immune checkpoint-based therapies. Exosomes are considered as "treasure troves" of diagnostic biomarkers. We are developing technologies to identify exosome-based biomarkers in blood that help monitor tumor progression and patient response to immunotherapy.
Throughout our research, we take a multidisciplinary approach that combines biochemistry, biophysics, structure biology, molecular biology, genetics, cell biology, and immunology. We also integrate fundamental cell biology and clinical research, as we believe basic science and medicine can inspire and instruct each other.
Molecular mechanisms of exocytic trafficking, tumor invasion, and immune suppression
1. Molecular basis of exocytosis: Exocytosis is a basic cell biological process mediated by transport, docking, and fusion of secretory vesicles carrying proteins and lipids to the plasma membrane. Through exocytosis, hormones and neurotransmitters can be released. Also, through exocytosis, membrane proteins and lipids can be incorporated into specific domains of plasma membrane for cell surface expansion, cell growth, morphogenesis, and cell migration. Our research aims to address three fundamental questions in cell biology: (1) what is the molecular basis for exocytosis; (2) how do the secretory machinery functions in concert with cytoskeleton and small-GTP-binding proteins during cell polarization and cell migration; (3) how the basic cell biological processes mentioned above are implicated in diseases such as cancer and diabetes. One of our research interests is the evolutionarily conserved multi-protein complex, named the exocyst. The exocyst consists of eight components: Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84, and plays essential roles in secretory vesicle targeting and docking at the plasma membrane during exocytosis. The exocyst is specifically localized to sites of active exocytosis and polarized cell growth, and is a downstream effector of many small GTPases including Rab, Rho, and Ral. In addition, the exocyst is a direct target of many kinases in the cell. Under the control of these signaling proteins, the exocyst coordinates with actin cytoskeleton in many pathophysiological processes such as cytokinesis, ciliogenesis, cell migration, and tumor invasion.
2. Exosomes in cancer: We are studying the molecular mechanisms that regulate the biogenesis and secretion of exosomes, which are lipid-encapsulated small vesicles secreted by a wide variety of cells. Furthermore, we aim to understanding how cancer cell-derived exosomes and other types of extracellular vesicles influence tumor microenvironment to effectively promote tumor growth, metastasis and immune evasion. We recently found that tumor-derived exosomes carry the immune checkpoint protein PD-L1, and systemically suppress the immune system. We are currently investigating how oncogenic signals regulate the biogenesis of PD-L1 exosomes and how manipulating exosome trafficking could improve the response of cancer patients to immune checkpoint-based therapies. Exosomes are considered as "treasure troves" of diagnostic biomarkers. We are developing technologies to identify exosome-based biomarkers in blood that help monitor tumor progression and patient response to immunotherapy.
Throughout our research, we take a multidisciplinary approach that combines biochemistry, biophysics, structure biology, molecular biology, genetics, cell biology, and immunology. We also integrate fundamental cell biology and clinical research, as we believe basic science and medicine can inspire and instruct each other.
研究兴趣
论文共 191 篇作者统计合作学者相似作者
按年份排序按引用量排序主题筛选期刊级别筛选合作者筛选合作机构筛选
时间
引用量
主题
期刊级别
合作者
合作机构
Bin Wu,Di-Ao Liu,Lei Guan,Phyoe Kyawe Myint,LiKang Chin,Hien Dang, Ye Xu, Jinqi Ren,Ting Li,Ziyan Yu, Sophie Jabban,Gordon B. Mills,
Kshitiz Parihar, Seung-Hyun Ko,Ryan Bradley, Phillip Taylor, N. Ramakrishnan,Tobias Baumgart,Wei Guo,Valerie M. Weaver,Paul A. Janmey,Ravi Radhakrishnan
Mechanobiology in Medicinepp.100071, (2024)
Fan Yang, Md Naushad Akhtar,Duo Zhang,Rakan El-Mayta, Junyoung Shin,Jay F. Dorsey,Lin Zhang,Xiaowei Xu,Wei Guo, Stephen J. Bagley,Serge Y. Fuchs,Constantinos Koumenis,
SCIENCE ADVANCESno. 9 (2024): eadj4678-eadj4678
Kshitiz Parihar, Seung-Hyun Ko,Ryan Bradley, Phillip Taylor, N. Ramakrishnan,Tobias Baumgart,Wei Guo,Valerie M. Weaver,Paul A. Janmey,Ravi Radhakrishnan
Methods in Enzymology (2024)
Diagnostic pathologyno. 1 (2023): 71-12
BLOOD CANCER DISCOVERYno. 1 (2023): 5-7
crossref(2023)
crossref(2023)
crossref(2023)
加载更多
作者统计
合作学者
合作机构
D-Core
- 合作者
- 学生
- 导师
数据免责声明
页面数据均来自互联网公开来源、合作出版商和通过AI技术自动分析结果,我们不对页面数据的有效性、准确性、正确性、可靠性、完整性和及时性做出任何承诺和保证。若有疑问,可以通过电子邮件方式联系我们:report@aminer.cn