Huabo su, PhD
Associate Professor, Vascular Biology Center
|More about Dr Su|
Post-translational modifications (PTMs) by a family of small protein modifiers, including ubiquitin (Ub) and Ub-like proteins, represent a vital mechanism regulating protein function and are integral to cellular homeostasis. Recent studies have consistently proven the fundamental importance of these PTMs in normal cell function and their implications in a wide array of diseases ranging from cancers, viral diseases, to neurodegenerative disorders and cardiovascular diseases. However, the biological functions of novel ubiquitin-like proteins in the heart remain poorly understood.
We are particularly interested in the roles of NEDD8 (Neural precursor cell expressed, developmentally downregulated 8) and Ufm1 (Ubiquitin-like protein modifier 1), two novel Ub-like proteins, in the heart. NEDD8 and Ufm1 modify protein targets via their specific conjugation enzymes, termed neddylation and ufmylation, respectively. Our research aims to address three major questions: 1) does neddylation or ufmylation have any roles in the developing and stressed hearts? 2) how does neddylation or ufmylation control cardiomyocyte function and survial? and 3) what cellular proteins are modified by NEDD8 or Ufm1 and how such modifications alter their molecular, cellular, organismal functions? We use a combination of novel genetically engineered mouse models with advanced molecular, cellular, physiological and pathological, and proteomic descriptors to tackle these questions.
Jie Li, M.D., Ph.D. - Assistant Research Scientist
Jianqiu Zou, Ph.D. - Assistant Research Scientist
Rodney Littlejohn, - M.D./Ph.D. candidate
Yali Yao, M.S. - Research Assistant
Yuan Wen, Ph.D. - Visiting Scholar
Zou J, Ma W, Littlejohn R, Li J, Stansfield BK, Kim IM, Liu J, Zhou J, Weintraub NL, Su H*. Transient inhibition of neddylation at neonatal stage evokes reversible cardiomyopathy and predisposes the heart to isoproterenol-induced heart failure. Am J Physiol Heart Circ Physiol. 2019 Mar 29. doi: 10.1152/ajpheart.00806.2018. [Epub ahead of print]. PMID: 30925068
Li J, Yue G, Ma W, Zhang A, Zou J, Cai Y, Tang X, Wang J, Liu J, Li H, Su H*. The
ufm1 specific ligase 1 regulates endoplasmic reticulum homeostasis and protects against
heart failure. Circ Heart Fail. 2018 Oct;11(10):e004917. doi: 10.1161/CIRCHEARTFAILURE.118.004917.
Zou J, Ma W, Li J, Littlejohn R, Zhou H, Kim IM, Fulton DJR, Chen W, Weintraub NL, Zhou J, Su H*. Neddylation is required for ventricular chamber maturation through repression of Hippo signaling. Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):E4101-E4110. PMID: 29632206.
Li J, Ma W, Yue G, Tang Y, Kim IL, Weintraub NL, Wang X, Su H*. Cardiac proteasome
functional insufficiency plays a pathogenic role in diabetic cardiomyopathy. J Mol
Cell Cardiol. 2017 Jan;102:53-60. PMID: 27913284.
Li J, Johnson JA, Su H*. Ubiquitin and ubiquitin-like proteins in cardiac disease and protection. Curr Drug Targets. 2018; 19(9):989-1002. doi: 10.2174/1389450117666151209114608. PMID: 26648080.
Su H, Li J, Zhang H, Ma W, Wei N, Liu J, Wang X. COP9 Signalosome Controls the Degradation
of Cytosolic Misfolded Proteins and Protects Against Cardiac Proteotoxicity. Circ
Res. 2015 Nov 6;117(11):956-66. PubMed PMID: 26383969.
Li J, Ma W, Li H, Hou N, Wang X, Kim IM, Li F, Su H*. NEDD8 Ultimate Buster-1 Long (NUB1L) Protein Suppresses Atypical Neddylation and Promotes Proteasomal Degradation of Misfolded Proteins. J Biol Chem. 2015 Sep 25;290(39):23850-62. PubMed PMID: 26260793.
Kandala S, Kim IM, Su H*. Neddylation and deneddylation in cardiac biology. Am J Cardiovasc Dis. 2014 Dec 29;4(4):140-58. PMID: 25628956.