Lab of Cardiovascular Signaling, Centenary Institute

Lab head: Xiangjian Zheng
Location: Centenary Institute (across the new CPC biulding)

We use mouse genetics, advaince inaging and cultured human cells to investigated the molecular mechanism of cardiovascular development and diseases. The current major focus is Cerebral Cavernous malformation, a vasscular disease in CNS causing stroke. 

Lab members: Xiangjian Zheng, Ph.D, Labe Head Jeremy Wong, Ph.D, Postdoc Peter Choi, Ph.D, Postdoc
Funding: NHMRC
Research approach equipment: Mouse genetics, micro-CT, Immunohistology, molecular biology

1.   Zhou Z, RawnsleyD, Goddard L, Pan W, Cao X, Jakus Z, Zheng H, Yang J, ArthurS, 

      WhiteheadKJ, LiD, Zhou B, Garcia BA, Zheng X* and Kahn ML*.  The cerebral

      cavernous malformation pathway controls cardiac development via regulation of

      endocardial MEKK3 signaling and KLF expression. Dev Cell 32(2): 168-180 (2015)

      (* co-corresponding author).


2.   Zheng X, Riant F, Bergametti F, Myers CD, Tang AT, KleavelandB, Pan W, Yang J,

      Tounier-Reserve E and Kahn ML. Cerebral cavernous malformations arise independent

      of heart-of-glass receptor. Stroke 45(5): 1505-09(2014).


3.   Zheng X, Xu C, Smith AO, Stratman AN, ZouZ, KleavelandB, YuanL, Didiku C, Skuli  N,

      ZaslavskyA, ChenM, Cheng L, DavisGE, and Kahn ML.  Dynamic regulation of cerebral

      cavernous malformation pathway controls cardiovascular stability and growth. Dev cell    

      23 (2): 342-355 (2012).


4.   Zheng X, Xu C, Di Lorenzo A, Kleaveland B, Zou Z, Seiler C, Chen M, Cheng L, XiaoJ,

      He J, Pack MA, Sessa WC and Kahn ML. CCM3 signaling through sterile 20-like kinases

      plays an essential role during zebrafish cardiovascular development and in human

      cerebral cavernous malformations. J Clin Invest. 120 (8): 2795-804 (2010).


5.  Kleaveland B, Zheng X, Liu JJ, Blum Y, Tung JJ, Zou Z,  Chen M, Guo L, Lu M, Zhou D,   

Kitajewski J, Affolter M, Ginsberg MH and Kahn M.  Regulation of cardiovascular development and integrity by the heart of glass-cerebral cavernous malformation protein pathway.  Nature Medicine, 15(2): 169-76 (2009).

micro-CT imaging of Cerebral Cavernous Malformation (CCM) in mouse models

Primary supervisor: Xiangjian Zheng

CCMs are vascular malformations that arise progressively in CNS and are major cause of stroke in younger patients. The only clinical treatment currently available for symptomatic CCM is surgical removal of lesions if they are accessible. Loss-of-function mutations in three genes, CCM1, CCM2 and CCM3, have been shown to cause CCM disease. We have generated mouse models for CCM disease by conditionally delete CCM genes in endothelium. We have also developed a protocol to use micro-CT to image CCM lesions in mouse brain.

This project will use the state-of-art imaging technology and mouse models of CCM, and apply our recently discovered molecular insights of CCM signaling, to test genetic and pharmacological approaches in preventing CCM lesion formation. This will be a project suitable for student with good skills in imaging software and with enthusiasm in learning mouse genetics and understanding human disease in mouse models. 

Discipline: Pathology