Dr. Zhang's research focuses on the molecular genetic mechanisms of neurodegeneration in Alzheimer’s and Parkinson’s diseases.
Dr. Zhang earned his Ph.D. in molecular pathology from the University of California, San Diego in 1995.
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Antioxidants protect PINK1-dependent dopaminergic neurons in Drosophila.
Wang D, Qian L, Xiong H, Liu J, Neckameyer WS, Oldham S, Xia K, Wang J, Bodmer R, Zhang Z
Proc Natl Acad Sci U S A. 2006 Sep 5;103(36):13520-5
Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease.
Tang B, Xiong H, Sun P, Zhang Y, Wang D, Hu Z, Zhu Z, Ma H, Pan Q, Xia JH, Xia K, Zhang Z
Hum Mol Genet. 2006 Jun 1;15(11):1816-25
Transcriptional regulation of PEN-2, a key component of the gamma-secretase complex, by CREB.
Wang R, Zhang YW, Sun P, Liu R, Zhang X, Zhang X, Xia K, Xia J, Xu H, Zhang Z
Mol Cell Biol. 2006 Feb;26(4):1347-54
Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism.
Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X
Cell. 2002 Mar 22;108(6):837-47
Presenilins are required for gamma-secretase cleavage of beta-APP and transmembrane cleavage of Notch-1.
Zhang Z, Nadeau P, Song W, Donoviel D, Yuan M, Bernstein A, Yankner BA
Nat Cell Biol. 2000 Jul;2(7):463-5
Zhuohua Zhang's Research Focus
Psoriasis, Alzheimer's Disease, Parkinson's Disease
Neurodegenerative diseases are currently uncurable disorders caused by the deterioration of certain nerve cells (neurons) that result in function abnormally, eventually bringing about death of these cells. Alzheimer’s disease and Parkinson’s disease are two most common neurodegenerative diseases caused by neuronal degeneration in the central nervous system. Dr. Zhang's research aims at understanding mechanisms of neurodegeneration in Alzheimer’s disease and Parkinson’s disease via studying the molecular functions of genes linked to the two diseases and dysfunction caused by their respective pathogenic mutants. The knowledge gained from Dr. Zhang’s research will be helpful in better understanding neurodegenerative diseases, and ultimately, designing better treatments.
Zhuohua Zhang's Research Report
Cellular and Molecular Mechanisms of Neurodegeneration
The research focus in our laboratory is to understand the cellular and molecular mechanisms of neurodegenerative diseases. We are particular interested in the role of signaling pathways in regulating protein degradation and in preventing neurons from degeneration in the central nervous system.
Pathogenesis of Parkinson’s disease (PD): Parkinson’s disease is the most frequent neurodegenerative movement disorder. The pathological hallmarks of PD patients include progressive loss of dopaminergic neurons in the substantia nigra pars compacta as well as the presence of ubiquitin-positive Lewy neurites and Lewy bodies in the remaining neurons. We recently found that parkin, PINK1 and DJ-1, three proteins linked to recessive familial form of PD, form a novel E3 ligase complex to promote ubiquitination and degradation of parkin substrates. Pathogenic parkin and PINK1 mutants impair this degradation ability. We have further identified what is to our knowledge the first early onset recessive PD case with digenic inheritance of PINK1 and DJ-1 mutations, providing in vivo evidence of functional interaction of PINK1 and DJ-1. We have also generated a novel fly model of PD by inactivation of
PINK1 using siRNA technology. In this model, inactivation of
results in loss of DA neurons and ommatidial degeneration via an oxidative stress mechanism.
Regulation of γ-secretases: One of the pathological hallmarks of Alzheimer’s disease is plaque formation that is extrecellular deposition of amyloid β peptides. γ-Secretases are key enzymes for amyloid β production. We have previously demonstrated an essential role of presenilins in γ-secretase activity and production of amyloid β peptides. In recent studies, we further defined the transcriptional regulation of γ-secretase components, aph-1 and pen-2.
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About Zhuohua Zhang
Zhuohua Zhang earned his Ph.D. in molecular pathology from the University of California, San Diego in 1995. He worked as a postdoctoral fellow at Sanford-Burnham Medical Research Institute, and received further postdoctoral training in the Department of Neurology at Harvard Medical School from 1996-2000. Dr. Zhang was recruited to Sanford-Burnham Medical Research Institute as Assistant Professor in July 2000.