SHEN, Jie, PhD          
          Associate Professor of Neurology
EDUCATION/TRAINING 

East China Normal University, Shanghai, China B.S. 1984 Biochemistry
University of Virginia, Charlottesville, VA Ph.D. 1995 Molecular Biology
Mass. Institute of Technology, Cambridge, MA Postdoc. 1997 Genetics/Neurobiology
 
A. Positions and Honors:
1988-1994  Graduate student in the laboratory of Professor Jay Hirsh, University of Virginia
1995-1997  Postdoctoral Fellow in the laboratory of Professor Susumu Tonegawa, MIT
1998-2004  Assistant Professor of Neurology, Harvard Medical School 
2004-   Associate Professor of Neurology, Harvard Medical School

Professional Membership and Activities:
1996-   Member, AAAS, Society of Neuroscience
2001-   Editorial Board, Journal of Molecular Neuroscience
   Editorial Board, Neuromolecular Medicine
2002-   Editorial Board, Neurodegenerative Diseases
2003-   Member, The American Society for Biochemistry and Molecular Biology (ASBMB)
   The Federation of American Societies for Experimental Biology (FASEB)
2005 - 2007  Member, SYN (MDCN1) study section, National Institutes of Health
2005   Organizer of the HCNR symposium “Memory and Dementia” at HMS
2008-   Co-organizer of the Gordon Research Conference on “Neurobiology of Brain Disorders”

B. Selected peer-reviewed publications:
Shen J, Beall CJ, Hirsh J.  Tissue-specific alternative splicing of the Drosophila dopa decarboxylase gene is affected by heat shock.  Mol Cell Biol 1993; 13: 4549-4555.
Shen J, Hirsh J.  Cis-regulatory sequences responsible for alternative splicing of the Drosophila dopa decarboxylase gene.  Mol Cell Biol 1994; 14: 7385-7393.
Shen J, Zu K, Cass C, Beyer A, Hirsh J.  Exon skipping by overexpression of a Drosophila heterogeneous nuclear ribonucleoprotein in vivo.  Proc Natl Acad Sci USA 1995; 92: 1822-1825.
Shen J, Bronson RT, Chen DF, Xia W, Selkoe DJ, Tonegawa S.  Skeletal and CNS defects in Presenilin-1 deficient mice.  Cell 1997; 89: 629-639.
Xia W, Zhang J, Ostaszewski BL, Kimberly WT, Seubert P, Koo EH, Shen J, Selkoe DJ.  Presenilin regulates the processing of APP C-terminal fragments and the generation of amyloid ?-protein in ER and Golgi.  Biochemistry 1998; 37:16465-16471.
Song W, Nadeau P, Yuan M, Yang X, Shen J, Yankner BA.  Proteolytic release and nuclear translocation of Notch-1 are induced by presenilin-1 and impaired by pathogenic presenilin-1 mutations. Proc. Natl. Acad. Sci. USA, 1999; 96:6959-63.
Yu H, Kessler J, Shen J.  Heterogeneous populations of ES cells in the generation of a floxed Presenilin-1 allele.  Genesis, 2000; 26:5-8.
Handler M, Yang X, Shen J.  Presenilin-1 regulates neuronal differentiation during neurogenesis. Development, 2000,127:2593-2606.
Yoo AS, Cheng I, Chung, S, Grenfell TZ, Pack-Chung E, Handler M, Shen J, Xia W, Tesco G, Saunders AJ, Ding K, Frosch MP, Tanzi RE, Kim T.  Presenilin-mediated modulation of capacitative calcium entry. Neuron 2000, 27:561-72.
Yang X, Handler M, Shen J. Role of presenilin-1 in murine neural development.  Annals NY Acad. Sci. 2000; 920: 165-170.
Singh N, Talalayeva Y, Tsiper M, Romanov V, Dranovsky A, Colflesh D, Rudamen G, Vitek MP, Shen J, Yang S, Goldgaber D, Schwarzman AL. The role of Alzheimer’s disease-related presenilin 1 in intercellular adhesion.  Experimental Cell Res 2001; 263:1-13.
Sharon R, Goldberg MS, Bar-Josef I, Betensky RA, Shen J, Selkoe DJ. Alpha-Synuclein occurs in lipid-rich high molecular weight complexes, binds fatty acids, and shows homology to the fatty acid-binding proteins. Proc Natl Acad Sci U S A. 2001; 98:9110-5.
Yu H, Saura C, Choi S, Sun LD, Yang X, Handler M, Kawarabayashi T, Younkin L, Fedeles B, Wilson MA, Younkin S, Kandel E, Kirkwood A, Shen J.  APP processing and synaptic plasticity in presenilin-1 conditional knockout mice. Neuron 2001; 31:713-26.
Fujiwara H, Hasegawa M, Dohmae N, Kawashima A, Masliah E, Goldberg MS, Shen J, Takio K, Iwatsubo T. alpha-Synuclein is phosphorylated in synucleinopathy lesions.  Nat Cell Biol 2002; 4:160-4.
Goldberg MS, Fleming SM, Palacino JJ, Cepeda C, Lam HA, Bhatnagar A, Meloni EG, Wu N, Ackerson LC, Klapstein GJ, Gajendiran M, Roth BL, Chesselet M, Maidment NT, Levine MS and Shen J. Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. JBC 2003, 278:43628-35.
Yang X, Klein R, Tian X, Cheng H, Kopan R and Shen J.  Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathway.  Dev Biol 2004, 269:81-94.
Palacino, JJ, Saji D, Goldberg MS, Krauss S, Motz C, Klose J, Shen J.  Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. JBC 2004, 279:18614-22.
Saura CA, Choi S, Beglopoulos V, Zhang D, Malkani S, Rao BSS, Chattarji S, Kelleher RJ, Kandel ER, Duff K, Kirkwood A and Shen J. Loss of presenilin function in the adult brain causes memory and synaptic plasticity impairments and age-dependent neurodegeneration. Neuron 2004, 42:23-36.
 *See associated minireview in Neuron 2004, 42:189-92.
Shen J and Cookson M. Mitochondria and dopamine: new insights into recessive parkinsonism.  Neuron 2004, 43:301-4.
Beglopoulos V, Sun X, Saura CA, Lemere CA, Kim RD and Shen J. Increased inflammatory responses and reduced ?-amyloid production in presenilin conditional knockout mice. JBC 2004, 279: 46907-14.
Shen J.  Protein kinases linked to the pathogenesis of Parkinson’s disease.  Neuron 2004, 44:575-7.
Pan Y, Lin M, Tian X, Cheng H, Gridley T, Shen J, Kopan R. ?-Secretase functions through Notch signaling to maintain the lineally related skin appendages but is not required for patterning or their initial morphogenesis. Dev Cell 2004,7:731-743.
Beglopoulos V and Shen J. Gene targeting technologies for the study of neurological disorders, NMM 2004, 6:13-30.
Wines ME, Handler M and Shen J. Role of presenilin-1 in cortical lamination and survival of Cajal-Retzius neurons. Dev Biol 2005, 277:332-346.
Goldberg MS, Pisani A, Haburcak M, Vertherms, TA, Kitada T, Costa C, Tong Y, Martella G, Tscherter A, Martins A, Bernardi G, Roth BL, Pothos EN, Calabresi P and Shen J. Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial parkinsonism-linked gene DJ-1. Neuron 2005, 45: 489-96.
 *See accompanying preview in Neuron 2005, 45: 479-81.
Zhang L, Lee J, Song L, Sun X, Shen J, Terracina G and Parker EM. Characterization of the reconstituted gamma-secretase complex from Sf9 co-expressing presenilin-1, nacastrin, aph-1a and pen-2.  Biochemistry 2005, 44:4450-7.
Pardossi-Piquard R, Petit A, Kawarai T, Sunyach C, da Costa CA, Vincent B, Ring S, D’Adamio L, Shen J, Muller U, Hyslop P, Checler F.  Presenilin-dependent transcriptional control of the A?-degrading enzyme neprilysin by intracellular domains of ?APP and APLP. Neuron 2005, 46:541-554.
Wines-Samuelson M and Shen J. Presenilins in the developing, adult and aging cerebral cortex. The Neuroscientist 2005, 11:441-51.
Saura CA, Chen G, Malkani S, Choi S, Takahashi RH, Gouras GK, Kirkwood A, Morris RGM and Shen J. Conditional inactivation of presenilin-1 prevents amyloid accumulation and temporarily rescues associative and working memory impairments in APP transgenic mice.  J. Neurosci. 2005, 20:6755-64.
Sun X, Beglopoulos V, Mattson M and Shen J. Hippocampal memory impairments caused by familial Alzheimer’s disease-linked M146V mutation.  Neurodegenerative Diseases 2005, 5:6-15.
Pan Y, Liu Z, Shen J and Kopan R. Notch1 and 2 cooperate in limb ectoderm to receive an early Jagged2 signal regulating interdigital apoptosis. Dev Biol 2005, 286: 472-82.
Grimm MOW, Grimm HS, Patzold AJ, Zinser EG, Halonen R, Duering M, Tschape JA, Muller U, De Strooper B, Shen J, Hartmann T. Regulation of cholesterol and sphingomyelin metabolism by amyloid-? and presenilin. Nat Cell Biol 2005, 7:1118-23.
Beglopoulos V and Shen J. Regulation of CREB/CBP signaling by presenilins: prospects for therapy of Alzheimer’s disease.  Trends in Pharmacol Sci 2006, 27:33-40.
Goldberg M and Shen J. Mouse models of recessive parkinsonism, book chapter, “Parkinson’s Disease: Genetics and Pathogenesis.”  Editor: Ted Dawson.  Taylor & Francis Group, LLC.
Yang X, Tomita T, Kopan R and Shen J. Notch1 signaling influences V2 interneuron and motor neuron development in the spinal cord.  Dev Neurosci 2006, 28:102-117.
Pisani A, Martella G, Tscherter A, Costa C, Mercuri NB, Shen J, and Calabresi P. Enhanced sensitivity of DJ-1 deficient dopaminergic neurons to energy metabolism impairment: role of Na+/K+ ATPase. Neurobiol of Dis 2006, 23:54-60.
Rosen KM, Veereshwarayya V, Moussa CE, Fu Q, Goldberg MS, Schlossmacher MG, Shen J, Querfurth HW. Parkin protects against mitochondrial toxins and beta-amyloid accumulation in skeletal muscle cells. J Biol Chem 2006, 281:12809-16.
Kuo CT, Mirzadeh Z, Soriano-Navarro M, Rasin M, Wang D, Shen J, Sestan N, Garcia-Verdugo J, Alvarez-Buylla A, Jan LY, Jan YN. Postnatal Deletion of Numb/Numblike reveals repair and remodeling capacity in the subventricular neurogenic niche. Cell 2006, 127:1253-64.
Shen J and Kelleher RJ.  The presenilin hypothesis of Alzheimer’s disease: Evidence for a loss-of-function pathogenic mechanism. Proc Natl Acad Sci U S A. 2007, 104: 403-9.
Yamaguchi H and Shen J.  Absence of dopaminergic neuronal degeneration and oxidative damage in aged DJ-1-deficient mice.  Molecular Neurodegeneration 2007, 2:10.
Kitada T, Pisani A, Porter DR, Yamaguchi H, Tscherter A, Martella G, Bonsi P, Zhang C, Pothos EN, and Shen J. Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice. Proc Natl Acad Sci U S A. 2007, 104:11441-6.
Maraver A., Tadokoro CE, Badura ML, Shen J, Serrano M, and Lafaille JJ. Effect of Presenilins in the apoptosis of thymocytes and homeostasis of CD8+ T cells.  Blood 2007, 110:3218-25.
Del Barrio MG, Taveira-Marques R, Muroyama Y, Yuk DI, Li S, Wines-Samuelson M, Shen J, Smith HK, Xiang M, Rowitch D, and Richardson WD. A regulatory network involving Foxn4, Mash-1 and Delta-like 4/Notch-1 generates V2a and V2b spinal interneurons from a common progenitor pool. Development 2007, 134:3427-36.
Cookson MR, Dauer W, Dawson T, Fon E, Guo M, Shen J. The roles of kinases in familial Parkinson’s disease. J. Neurosci. 2007, 27(44):11865-8.
Yagi T, Giallourakis C, Mohanty S, Scheidig C, Shen J, Zheng H, Xavier RJ, Shaw AC.  Defective signal transduction in B lymphocytes lacking presenilin proteins. Proc Natl Acad Sci U S A. 2008, Published on-line Jan 14, 2008.
Kim WY and Shen J. Presenilins are required for maintenance of neural stem cells in the developing brain. Molecular Neurodegeneration 2008, in press.