Jiyan Ma

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Associate Professor

Ph.D. - University of Illinois, Chicago
Post Doctoral - University of Chicago

We are studying the Transmissible Spongiform Encephalopathies (TSEs), also known as prion disease. This is a group of unique neurodegenerative disorders that can be manifested as sporadic, dominantly inheritable, or infectious diseases. It is still not clear how neurons degenerate in prion disease. The involvement of prion protein, PrP - a cell surface localized normal cellular glycoprotein, in the pathogenesis of prion disease has been clearly demonstrated. Our recent work has revealed that misfolding of PrP in the endoplasmic reticulum (ER), subsequent retro-translocation of it to the cytosol, and the accumulation of PrP in the cytosol can lead to rapid neuronal death. Currently, we are characterizing this process and trying to understand its role in prion disease.

We have developed a transgenic mouse model of neurodegeneration caused by expressing PrP in the cytosol. Further characterization of this mouse model and generating more transgenic mice expressing cytosolic PrP under the control of different promoters will help us to understand the molecular and cellular mechanisms of the neurodegeneration caused by cytosolic PrP.

We are also using a variety of methods to study the cell biology of PrP, particularly, the misfolding of PrP in the ER and its retro-translocation to the cytosol. We are interested in the potential influence of molecular chaperones on PrP misfolding, retro-translocation, and the neurotoxicity caused by its accumulation in the cytosol.

Prion disease is one of the many neurodegenerative diseases involving accumulation of aberrantly folded proteins. The long-term goal of our research is to understand how these diseases occur, why these diseases occur in the neuronal system, and what is the influence of aging on these diseases.

Recent Publications:

• Faas H, Jackson WS, Borkowski AW, Wang X, Ma J, Lindquist S and Jasanoff A (2009) "Context-dependent perturbation of neural systems in transgenic mice expressing a cytosolic prion protein." Neuroimage Oct 14. [Epub ahead of print]
• Wang X, Bowers SL, Wang F, Pu XA, Nelson RJ and Ma J (2009) "Cytoplasmic prion protein induces forebrain neurotoxicity" Biochim Biophys Acta. 1792(6):555-63.
• Cornwell DG and Ma J (2008) "Nutritional benefit of olive oil: the biological effects of hydroxytyrosol and its arylating quinone adducts" J Agric Food Chem 56(19):8774-86.
• Cornwell DG and Ma J (2007) "Studies in vitamin E: biochemistry and molecular biology of tocopherol quinones" Vitam Horm. 76:99-134.
• Wang F, Yang F, Hu Y, Wang X, Wang X, Jin C and Ma J (2007) "Lipid Interaction Converts Prion Protein to a PrP(Sc)-like Proteinase K-Resistant Conformation under Physiological Conditions" Biochemistry. 46(23):7045-53.
• Wang X, Wang F, Arterburn L, Wollmann R and Ma J (2006) "The interaction between cytoplasmic PrP and the hydrophobic lipid core of membrane correlates with neurotoxicity" J Biol Chem 281(19):13478-84.
• Wang X, Thomas B, Sachdeva R, Arterburn L, Frye L, Hatcher PG, Cornwell DG and Ma J (2006) "Mechanism of arylating quinone toxicity involving Michael adduct formation and induction of endoplasmic reticulum stress" PNAS 103(10):3604-09.
• Wang X, Wang F, Sy MS and Ma J (2005) "Calpain and other cytosolic proteases can contribute to the degradation of retro-translocated prion protein in the cytosol" J Biol Chem 280(1):317-25.
• Sachdeva R, Thomas B, Wang X, Ma J, Jones KH, Hatcher PG and Cornwell DG (2005) "Tocopherol metabolism using thermochemolysis: chemical and biological properties of gamma-tocopherol, gamma-carboxyethyl-hydroxychroman, and their quinones" Chem Res Toxicol 18(6):1018-25.
• Ma J and Lindquist S (2002) "Conversion of PrP to a self-perpetuating PrPSc-like conformation in the cytosol" Science 298(5599):1785-8.
• Ma J, Wollmann R and Lindquist S (2002) "Neurotoxicity and neurodegeneration when PrP accumulates in the cytosol" Science 298(5599):1781-5.