共 49 条
Caveolae-dependent Endocytosis Is Required for Class A Macrophage Scavenger Receptor-mediated Apoptosis in Macrophages
被引:102
作者:

Zhu, Xu-Dong
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Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China
Nanjing Med Univ, Inst Reprod Med, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Zhuang, Yan
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Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Ben, Jing-Jing
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Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Qian, Ling-Ling
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Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Huang, Han-Peng
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Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Bai, Hui
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h-index: 0
机构:
Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Sha, Jia-Hao
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h-index: 0
机构:
Nanjing Med Univ, Inst Reprod Med, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

He, Zhi-Gang
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h-index: 0
机构:
Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci, Boston, MA 02115 USA Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Chen, Qi
论文数: 0 引用数: 0
h-index: 0
机构:
Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China
Nanjing Med Univ, Inst Reprod Med, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China
机构:
[1] Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China
[2] Nanjing Med Univ, Inst Reprod Med, Nanjing 210029, Peoples R China
[3] Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci, Boston, MA 02115 USA
基金:
中国国家自然科学基金;
关键词:
LOW-DENSITY-LIPOPROTEIN;
FOAM CELL-FORMATION;
CYTOPLASMIC DOMAIN;
LIPID UPTAKE;
PLASMA-MEMBRANE;
CLATHRIN;
ATHEROSCLEROSIS;
INTERNALIZATION;
BINDING;
CHOLESTEROL;
D O I:
10.1074/jbc.M110.145888
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
SR-A (classAmacrophage scavenger receptor) is a transmembrane receptor that can bind many different ligands, including modified lipoproteins that are relevant to the development of vascular diseases. However, the precise endocytic pathways of SR-A/mediated ligands internalization are not fully characterized. In this study, we show that the SR-A/ligand complex can be endocytosed by both clathrin-and caveolae-dependent pathways. Internalizations of SR-A-lipoprotein (such as acLDL) complexes primarily go through clathrin-dependent endocytosis. In contrast, macrophage apoptosis triggered by SR-A-fucoidan internalization requires caveolae-dependent endocytosis. The caveolae-dependent process activates p38 kinase and JNK signaling, whereas the clathrin-mediated endocytosis elicits ERK signaling. Our results suggest that different SR-A endocytic pathways have distinct functional consequences due to the activation of different signaling cascades in macrophages.
引用
收藏
页码:8231 / 8239
页数:9
相关论文
共 49 条
[1]
Tyrosine phosphorylation of caveolin-1 in the endothelium
[J].
Aoki, T
;
Nomura, R
;
Fujimoto, T
.
EXPERIMENTAL CELL RESEARCH,
1999, 253 (02)
:629-636

Aoki, T
论文数: 0 引用数: 0
h-index: 0
机构: Nagoya Univ, Sch Med, Dept Anat & Mol Cell Biol, Showa Ku, Nagoya, Aichi 4668550, Japan

Nomura, R
论文数: 0 引用数: 0
h-index: 0
机构: Nagoya Univ, Sch Med, Dept Anat & Mol Cell Biol, Showa Ku, Nagoya, Aichi 4668550, Japan

Fujimoto, T
论文数: 0 引用数: 0
h-index: 0
机构: Nagoya Univ, Sch Med, Dept Anat & Mol Cell Biol, Showa Ku, Nagoya, Aichi 4668550, Japan
[2]
Glucose-regulated protein 78 inhibits scavenger receptor A-mediated internalization of acetylated low density lipoprotein
[J].
Ben, Jingjing
;
Gao, Song
;
Zhu, Xudong
;
Zheng, Yuan
;
Zhuang, Yan
;
Bai, Hui
;
Xu, Yong
;
Ji, Yong
;
Sha, Jiahao
;
He, Zhigang
;
Chen, Qi
.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,
2009, 47 (05)
:646-655

Ben, Jingjing
论文数: 0 引用数: 0
h-index: 0
机构:
Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China
Nanjing Med Univ, Inst Reprod Med, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Gao, Song
论文数: 0 引用数: 0
h-index: 0
机构:
Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Zhu, Xudong
论文数: 0 引用数: 0
h-index: 0
机构:
Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Zheng, Yuan
论文数: 0 引用数: 0
h-index: 0
机构:
Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Zhuang, Yan
论文数: 0 引用数: 0
h-index: 0
机构:
Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Bai, Hui
论文数: 0 引用数: 0
h-index: 0
机构:
Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Xu, Yong
论文数: 0 引用数: 0
h-index: 0
机构:
Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Ji, Yong
论文数: 0 引用数: 0
h-index: 0
机构:
Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Sha, Jiahao
论文数: 0 引用数: 0
h-index: 0
机构:
Nanjing Med Univ, Inst Reprod Med, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

He, Zhigang
论文数: 0 引用数: 0
h-index: 0
机构:
Harvard Univ, Childrens Hosp, Sch Med, Div Neurosci, Boston, MA 02115 USA Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China

Chen, Qi
论文数: 0 引用数: 0
h-index: 0
机构:
Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China
Nanjing Med Univ, Inst Reprod Med, Nanjing 210029, Peoples R China Nanjing Med Univ, Atherosclerosis Res Ctr, Key Lab Human Funct Genom, Nanjing 210029, Peoples R China
[3]
Conserved domains of the class A scavenger receptors: evolution and function
[J].
Bowdish, Dawn M. E.
;
Gordon, Siamon
.
IMMUNOLOGICAL REVIEWS,
2009, 227
:19-31

Bowdish, Dawn M. E.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

Gordon, Siamon
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
[4]
Procaspase 8 and Bax Are Up-regulated by Distinct Pathways in Streptococcal Pyrogenic Exotoxin B-induced Apoptosis
[J].
Chang, Chia-Wen
;
Tsai, Wan-Hua
;
Chuang, Woei-Jer
;
Lin, Yee-Shin
;
Wu, Jiunn-Jong
;
Liu, Ching-Chuan
;
Tsai, Pei-Jane
;
Lin, Ming T.
.
JOURNAL OF BIOLOGICAL CHEMISTRY,
2009, 284 (48)
:33195-33205

Chang, Chia-Wen
论文数: 0 引用数: 0
h-index: 0
机构:
Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci, Tainan 701, Taiwan
Natl Cheng Kung Univ, Coll Med, Dept Biochem, Tainan 701, Taiwan Tzu Chi Univ, Sch Med, Inst Med Sci, Hualien 97004, Taiwan

Tsai, Wan-Hua
论文数: 0 引用数: 0
h-index: 0
机构:
Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci, Tainan 701, Taiwan
Natl Cheng Kung Univ, Coll Med, Dept Biochem, Tainan 701, Taiwan Tzu Chi Univ, Sch Med, Inst Med Sci, Hualien 97004, Taiwan

Chuang, Woei-Jer
论文数: 0 引用数: 0
h-index: 0
机构:
Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci, Tainan 701, Taiwan
Natl Cheng Kung Univ, Coll Med, Dept Biochem, Tainan 701, Taiwan Tzu Chi Univ, Sch Med, Inst Med Sci, Hualien 97004, Taiwan

Lin, Yee-Shin
论文数: 0 引用数: 0
h-index: 0
机构:
Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci, Tainan 701, Taiwan
Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, Tainan 701, Taiwan Tzu Chi Univ, Sch Med, Inst Med Sci, Hualien 97004, Taiwan

Wu, Jiunn-Jong
论文数: 0 引用数: 0
h-index: 0
机构:
Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci, Tainan 701, Taiwan
Natl Cheng Kung Univ, Coll Med, Dept Med Lab Sci & Biotechnol, Tainan 701, Taiwan Tzu Chi Univ, Sch Med, Inst Med Sci, Hualien 97004, Taiwan

论文数: 引用数:
h-index:
机构:

论文数: 引用数:
h-index:
机构:

Lin, Ming T.
论文数: 0 引用数: 0
h-index: 0
机构:
Tzu Chi Univ, Sch Med, Inst Med Sci, Hualien 97004, Taiwan Tzu Chi Univ, Sch Med, Inst Med Sci, Hualien 97004, Taiwan
[5]
The association of epsin with ubiquitinated cargo along the endocytic pathway is negatively regulated by its interaction with clathrin
[J].
Chen, H
;
De Camilli, P
.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
2005, 102 (08)
:2766-2771

Chen, H
论文数: 0 引用数: 0
h-index: 0
机构: Yale Univ, Sch Med, Boyer Ctr Mol Med, Dept Cell Biol, New Haven, CT 06536 USA

De Camilli, P
论文数: 0 引用数: 0
h-index: 0
机构: Yale Univ, Sch Med, Boyer Ctr Mol Med, Dept Cell Biol, New Haven, CT 06536 USA
[6]
The di-leucine motif contributes to class A scavenger receptor-mediated internalization of acetylated lipoproteins
[J].
Chen, Yaoyu
;
Wang, Xiaohua
;
Ben, Jingjing
;
Yue, Shen
;
Bai, Hui
;
Guan, Xiaoxiang
;
Bai, Xiaoming
;
Jiang, Li
;
Ji, Yong
;
Fan, Leming
;
Chen, Qi
.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,
2006, 26 (06)
:1317-1322

Chen, Yaoyu
论文数: 0 引用数: 0
h-index: 0
机构: Nanjing Med Univ, Inst Reprod Med, Nanjing, Peoples R China

Wang, Xiaohua
论文数: 0 引用数: 0
h-index: 0
机构: Nanjing Med Univ, Inst Reprod Med, Nanjing, Peoples R China

Ben, Jingjing
论文数: 0 引用数: 0
h-index: 0
机构: Nanjing Med Univ, Inst Reprod Med, Nanjing, Peoples R China

Yue, Shen
论文数: 0 引用数: 0
h-index: 0
机构: Nanjing Med Univ, Inst Reprod Med, Nanjing, Peoples R China

Bai, Hui
论文数: 0 引用数: 0
h-index: 0
机构: Nanjing Med Univ, Inst Reprod Med, Nanjing, Peoples R China

Guan, Xiaoxiang
论文数: 0 引用数: 0
h-index: 0
机构: Nanjing Med Univ, Inst Reprod Med, Nanjing, Peoples R China

Bai, Xiaoming
论文数: 0 引用数: 0
h-index: 0
机构: Nanjing Med Univ, Inst Reprod Med, Nanjing, Peoples R China

Jiang, Li
论文数: 0 引用数: 0
h-index: 0
机构: Nanjing Med Univ, Inst Reprod Med, Nanjing, Peoples R China

Ji, Yong
论文数: 0 引用数: 0
h-index: 0
机构: Nanjing Med Univ, Inst Reprod Med, Nanjing, Peoples R China

Fan, Leming
论文数: 0 引用数: 0
h-index: 0
机构: Nanjing Med Univ, Inst Reprod Med, Nanjing, Peoples R China

Chen, Qi
论文数: 0 引用数: 0
h-index: 0
机构:
Nanjing Med Univ, Inst Reprod Med, Nanjing, Peoples R China Nanjing Med Univ, Inst Reprod Med, Nanjing, Peoples R China
[7]
Proliferation versus migration in platelet-derived growth factor signaling -: The key role of endocytosis
[J].
De Donatis, Alina
;
Comito, Giusy
;
Buricchi, Francesca
;
Vinci, Maria C.
;
Parenti, Astrid
;
Caselli, Anna
;
Camici, Guido
;
Manao, Giampaolo
;
Ramponi, Giampietro
;
Cirri, Paolo
.
JOURNAL OF BIOLOGICAL CHEMISTRY,
2008, 283 (29)
:19948-19956

De Donatis, Alina
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy

Comito, Giusy
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy

Buricchi, Francesca
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy

Vinci, Maria C.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Florence, Dipartimento Farmacol Preclin & Clin, I-50134 Florence, Italy Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy

Parenti, Astrid
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Florence, Dipartimento Farmacol Preclin & Clin, I-50134 Florence, Italy Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy

Caselli, Anna
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy

Camici, Guido
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy

Manao, Giampaolo
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy

Ramponi, Giampietro
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy

Cirri, Paolo
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy Univ Florence, Dipartimento Sci Biochim, I-50134 Florence, Italy
[8]
A JNK-dependent pathway is required for TNFα-induced apoptosis
[J].
Deng, YB
;
Ren, XY
;
Yang, L
;
Lin, YH
;
Wu, XW
.
CELL,
2003, 115 (01)
:61-70

Deng, YB
论文数: 0 引用数: 0
h-index: 0
机构: Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA

Ren, XY
论文数: 0 引用数: 0
h-index: 0
机构: Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA

Yang, L
论文数: 0 引用数: 0
h-index: 0
机构: Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA

Lin, YH
论文数: 0 引用数: 0
h-index: 0
机构: Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA

Wu, XW
论文数: 0 引用数: 0
h-index: 0
机构:
Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA
[9]
Cholesterol-induced macrophage apoptosis requires ER stress pathways and engagement of the type A scavenger receptor
[J].
DeVries-Seimon, T
;
Li, YK
;
Yao, PM
;
Stone, E
;
Wang, YB
;
Davis, RJ
;
Flavell, R
;
Tabas, I
.
JOURNAL OF CELL BIOLOGY,
2005, 171 (01)
:61-73

DeVries-Seimon, T
论文数: 0 引用数: 0
h-index: 0
机构: Columbia Univ, Dept Med, New York, NY 10032 USA

Li, YK
论文数: 0 引用数: 0
h-index: 0
机构: Columbia Univ, Dept Med, New York, NY 10032 USA

Yao, PM
论文数: 0 引用数: 0
h-index: 0
机构: Columbia Univ, Dept Med, New York, NY 10032 USA

Stone, E
论文数: 0 引用数: 0
h-index: 0
机构: Columbia Univ, Dept Med, New York, NY 10032 USA

Wang, YB
论文数: 0 引用数: 0
h-index: 0
机构: Columbia Univ, Dept Med, New York, NY 10032 USA

Davis, RJ
论文数: 0 引用数: 0
h-index: 0
机构: Columbia Univ, Dept Med, New York, NY 10032 USA

Flavell, R
论文数: 0 引用数: 0
h-index: 0
机构: Columbia Univ, Dept Med, New York, NY 10032 USA

Tabas, I
论文数: 0 引用数: 0
h-index: 0
机构:
Columbia Univ, Dept Med, New York, NY 10032 USA Columbia Univ, Dept Med, New York, NY 10032 USA
[10]
Distinct endocytic pathways regulate TGF-β receptor signalling and turnover
[J].
Di Guglielmo, GM
;
Le Roy, C
;
Goodfellow, AF
;
Wrana, JL
.
NATURE CELL BIOLOGY,
2003, 5 (05)
:410-421

Di Guglielmo, GM
论文数: 0 引用数: 0
h-index: 0
机构:
Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Programme Mol Biol & Canc, Toronto, ON M5G 1X5, Canada Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Programme Mol Biol & Canc, Toronto, ON M5G 1X5, Canada

Le Roy, C
论文数: 0 引用数: 0
h-index: 0
机构:
Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Programme Mol Biol & Canc, Toronto, ON M5G 1X5, Canada Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Programme Mol Biol & Canc, Toronto, ON M5G 1X5, Canada

Goodfellow, AF
论文数: 0 引用数: 0
h-index: 0
机构:
Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Programme Mol Biol & Canc, Toronto, ON M5G 1X5, Canada Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Programme Mol Biol & Canc, Toronto, ON M5G 1X5, Canada

Wrana, JL
论文数: 0 引用数: 0
h-index: 0
机构:
Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Programme Mol Biol & Canc, Toronto, ON M5G 1X5, Canada Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Programme Mol Biol & Canc, Toronto, ON M5G 1X5, Canada