NAME: Wei, Chaoliang

POSITION TITLE: Professor of Cell Biology; Vice Director for Dept. of Cell Biology and Medical Genetics, Shenzhen University School of Medicine

EDUCATION/TRAINING

A.   Personal Statement

My long-standing research interests focus on the molecular mechanisms of calcium signaling, tumor metastasis and cardiac diseases. My lab is actively exploring how calcium signals regulate tumor-cell migration, and how RNA binding proteins control tumor metastasis and maintain cardiac physiologic function. Research in my lab has been supported by the one regular National Natural Science Foundation in China (NSFC). I have published >14 papers in professional, peer-reviewed journals. I am currently mentoring one postdoctoral fellow and two MSc candidates.

B.   Positions and Honors

Positions and Employment

0 4 /2016 – present       Professor, Vice Director for Dept. of Cell Biology and Medical Genetics, Shenzhen University School of Medicine, Shenzhen, China

Organizing D omestic Meetings

1.      Co-organizer, the 1^st  Chromatin biology Conference, Apr. 14-16 , 201 7 , Shenzhen

Other Experience and Honors

1.    2017 Second prize of the State Natural Science Award ( National ,4^th)

2.    2016 First prize in the Excellent Achievement Award for Scientific Research in Universities (Ministry of Education, 4^th)

3.    2011 National 100 Top PhD Thesis

4.    2009 First Bei Shizhang Young Biophysicist Award (National)

C.   Contributions to Science (*: corresponding/co-corresponding author)

A full list of my publications (in a total of 14) is enclosed at the end of this document.

1.    Calcium flickers steer cell migration

The calcium ion is the simplest and most versatile second messenger in biology. Harboring a myriad of calcium effector proteins, migrating cells display an exquisite multi-scaled and multi-layered architecture of intracellular calcium dynamics. In 2009, I detected a “hidden” calcium signal activity called “calcium flicker” in migrating fibroblasts (Nature, 2009). Calcium flickers are most active at the leading lamella of migrating cells, displaying a front-to-rear polarization. Calcium flicker activity is dually coupled to TRPM7 channels (sense local membrane tension) and IP3 receptor 2 (transduct chemoattractant signal). When exposed to a PDGF gradient perpendicular to cell movement, asymmetric calcium flicker activity develops across the lamella and promotes the turning of migrating fibroblasts. Because of wide influence of  the above paper, My mentor Dr. Heping Cheng and I were invited to write two corresponding reviews for the Canadian Journal of Physiology and Pharmacology, 2010 and Current Opinion in Cell Biology, 2012.  

1)    Wei CL*, Wang X, Chen M, Ouyang K, Song LS, Cheng H*. Calcium Flickers Steer Cell Migration. Nature 2009 Feb; 457(7231): 901-905.(Recommended by “Faculty of 1000”)

2)    Wei CL*, Wang XH, Chen M, et al. Flickering Calcium Microdomains Signal Turning of Migrating Cells. Canadian Journal of Physiology and Pharmacology 2010 Feb; 88(2): 105-110.

3)    Wei CL, Wang XH, Zheng M, et al. Calcium Gradients Underlying Cell Migration. Current Opinion in Cell Biology 2012 Apr; 24 (2): 254-261.

2.    Pivotal Role of RBFox2 in heart failure and transcriptional regulation

The RBFox family of RNA-binding proteins has been implicated in development and disease. At the molecular level, RBFox2 has been extensively characterized as a splicing regulator that recognizes the evolutionarily conserved UGCAUG motif in pre-mRNAs and regulate alternative splicing in a position-dependent manner. Our group reported that RBFox2 functions as a key splicing regulator during postnatal heart remodeling, and tissue-specific ablation of RBFox2 in the heart causes lethal dilated cardiomyopathy (Cell Reports, 2015). RBFox2 protein is potently decreased in a heart failure model induced by transverse aortic constriction, suggesting RBFox2 is a key stress sensor in the heart.

Increasing evidence suggests that diverse RNA binding proteins (RBPs) interact with regulatory RNAs to regulate transcription. Polycomb complex 2 interacts with RNA, but it has been unclear whether this process requires additional regulators. Our group reported that RBFox2 is a global regulator of PRC2 recruitment to active genes, particularly those with bivalent histone modifications, to mediate dynamic transcriptional control (Molecular Cell, 2016). 

1)    Wei CL, Qiu JS, Zhou Y, et al. Repression of the Central Splicing Regulator RBFox2 Is Functionally Linked to Pressure Overload-Induced Heart Failure. Cell Reports 2015 Mar; (10): 1521–1533.

2)    Wei CL, Xiao R,Chen L, et al. RBFox2 Binds Nascent RNA to Globally Regulate Polycomb Complex 2 Targeting in Mammalian Genomes. Molecular Cell, 2016, 62 (6) :875-889. (Recommended by “Faculty of 1000”)

D.   Research Support

Ongoing Research Support

NSFC (China) (81770227)                                         01/01/2018 to 12/31/2021

Chaoliang Wei, PI                                                         ￥590,000 (direct cost)

The mechanisms of regulation of RNA binding protein RBFox2 in the heart disease

E.    Peer-reviewed publications (*: corresponding author)

1. Wei CL*, Wang X, Chen M, Ouyang K, Song LS, Cheng H*. Calcium Flickers Steer Cell Migration. Nature 2009 Feb;

457(7231): 901-905.

2. Wei CL, Xiao R, Ch en L , et al. RBFox2 Binds Nascent RNA to Globally Regulate Polycomb Complex 2 Targeting in Mammalian Genomes. Molecular Cell 2016 , 62(6):875-889.

3. Wei CL, Wang XH, Zheng M, et al. Calcium Gradients Underlying Cell Migration. Current

Opinion in Cell Biology 2012 Apr; 24 (2): 254-261.

4. Wei CL, Qiu JS, Zhou Y, et al. Repression of the Central Splicing Regulator RBFox2 Is Functionally Linked to Pressure Overload-Induced Heart Failure. Cell Reports 2015 Mar; (10): 1521–1533.

5. Wei CL*, Wang XH, Chen M, et al. Flickering Calcium Microdomains Signal Turning of Migrating Cells. Canadian Journal of Physiology and Pharmacology 2010 Feb; 88(2): 105-110.

6. Chen L, Liu Z, Zhou B, Wei CL, et al. CELF RNA binding proteins promote axon regeneration In C. elegans and mammals through alternative splicing of Syntaxins. Elife 2016; 5: e16072. 

7. Xue YC, Ouyang KF, Huang J, Zhou Y, Ouyang H, Li HL, Wang G, Wu QJ,  Wei CL, Fu XD, et al. Direct Conversion of Fibroblasts to Neurons by Reprogramming PTB-Regulated MicroRNA Circuits. Cell 2013 Jan; 152 (1-2): 82-96.

8. Xiong Y, Huo YQ, Chen C, Zeng HY, Lu XF,  Wei CL, et al. Vascular Endothelial Growth Factor  (VEGF)  Receptor-2  Tyrosine  1175  Signaling Controls VEGF-induced  von  Willebrand Factor  Release  from  Endothelial  Cells  via  Phospholipase  C-gamma  1-and  Protein  Kinase A-dependent Pathways. Journal of Biological Chemistry 2009 Aug; 284 (35):23217-23224.

9. Yan Y, Liu J, Wei CL, et al. Bidirectional Regulation of Ca2+ Sparks by Mitochondria-Derived Reactive Oxygen Species in Cardiac Myocytes. Cardiovasc Res 2008 Jan; (77): 432 – 441. 

10.  Feng  Z, Wei  CL,  Chen  X,  et  al.  Essential  Role  of  Ca2+   Release  Channels  in Angiotensin II-Induced Ca2+ Oscillations and Mesangial Cell Contraction. Kidney Int. 2006 Jul;70(1):130-8.

11. Yan Y, Wei CL, Zhang WR, et al. Cross-Talk Between Calcium and Reactive Oxygen Species Signaling. Acta Pharmacol Sin. 2006 Jul; 27(7):821-6.

12. Yao LJ, Wang G, Ou-Yang KF,  Wei CL, et al. Ca2+  Sparks and Ca2+  Glows in Superior Cervical Ganglion Neurons. Acta Pharmacol Sin. 2006 Jul; 27(7):848-852.

13. Wang SQ,   Wei CL, Zhao G, Cheng HP, et al. Imaging Microdomain Ca2+ in Muscle Cells. Circ Res. 2004 Apr; 94(8):1011-22.

14. Guo Y, Wei CL, Hu JS, Ding MX, Chen JG. Fibrillarin Redistributes to the Spindle Poles and Partially   Colocalizes    with    NuMA   During    Mitosis.    Chinese   Science   Bulletin    2002 47(23):1995-1998.