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Philip Cy Wong, Ph.D.

Photo of Dr. Philip Cy Wong, Ph.D.

Professor of Pathology

Background

Dr. Philip Wong is a professor of pathology at the Johns Hopkins University School of Medicine. His research focuses on understanding the molecular mechanisms of neurodegenerative disorders, such as Alzheimer''s disease and amyotrophic lateral sclerosis (ALS).

Dr. Wong’s team takes a molecular/cellular approach, including transgenic, gene targeting and RNAi strategies in mice, to develop models that facilitate their understanding of pathogenesis of Alzheimer’s and ALS as well as the identification and validation of novel targets for mechanism-based therapeutics. The mouse models are instrumental for study of disease mechanisms as well as for design and testing of therapeutic strategies for AD and ALS.

He received his undergraduate degree in biochemistry and his Ph.D. in biochemistry and molecular biology from the University of Western Ontario in Canada. He completed a postdoctoral fellowship in cellular and molecular biology at the Johns Hopkins University School of Medicine in the Department of Biological Chemistry. Dr. Wong joined the Johns Hopkins faculty in 1994.

Dr. Wong is a member of the New York Academy of Sciences and the Society of Neuroscience and is a member of the editorial board for Neuro-Signals. Dr. Wong’s work has been recognized with the 2004 Zenith Fellow’s Award from the Alzheimer’s Association.

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Titles

  • Professor of Pathology
  • Professor of Neuroscience

Departments / Divisions

Education

Degrees

  • Ph.D., University of Western Ontario (Canada) (1989)

Additional Training

Johns Hopkins University, Baltimore, MD, 1993, Cellular/Molecular Biology

Research & Publications

Research Summary

Dr. Wong’s research program is designed to understand the molecular mechanisms and identification of new therapeutic targets of neurodegenerative diseases, particularly Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). With discoveries of genes linked to these diseases (mutant APP and PS in familial AD and mutant SOD1, dynactin p150glued ALS4 and ALS2 in familial ALS), his laboratory is taking a molecular/cellular approach, including transgenic, gene targeting and RNAi strategies in mice, to develop models that facilitate our understanding of pathogenesis of disease and the identification and validation of novel targets for mechanism-based therapeutics. Significantly, these mouse models are instrumental for study of disease mechanisms as well as for design and testing of therapeutic strategies for AD and ALS.

Lab

Dr. Wong’s lab is working on the role of Alzheimer’s b-secretase, BACE1 and APP signaling in learning and memory; the role of Alzheimer’s g-secretase, including its function as a tumor suppressor in the skin; and the molecular mechanism of motor neuron disease linked to mutations in dynactin p150glued,SOD1, ALS4 and ALS2 with a focus on alterations in axonal transport.

Lab Website: Philip Wong Lab

Selected Publications

Chow VW, Savonenko AV, Melnikova T, Kim H, Price DL, Li T and Wong PC. "Modeling an anti-amyloid combination therapy for Alzheimer's Disease." Science Translational Medicine 2:1-11, 2010

Hu X, Hicks CW, He W, Wong PC, Macklin WB, Trapp BD & Yan R "Bace1 modulates myelination in the central and peripheral nervous system." Nature Neuroscience, online November 12, 2006.

Laird FM, Cai H, Savonenko AV, Farah MH, He K, Melnikova T, Wen H, Chiang HC, Xu G, Koliatsos VE, Borchelt DR, Price DL, Lee H-K and Wong PC. "BACE1, a Major Determinant of Selective Vulnerability of the Brain to Amyloid-b Amyloidogenesis is Essential for Cognitive, Emotional and Synaptic Functions." J. Neuroscience 25:11693–11709, 2005.

Cai H, Lin X, Xie C, Laird FM, Lai C, Wen H, Chiang HC, Shim H, Farah M, Hoke A, Price DL, and Wong PC. "Loss of ALS2 function is insufficient to trigger motor neuron degeneration in knockout mice, but predisposes neurons to oxidative stress." J. Neuroscience 25:7567–7574, 2005.

Ma G, Li T, Price DL and Wong PC. "Aph-1a is the principal mammalian Aph-1 isoform present in g-secretase complexes during embryonic development." J. Neuroscience 25:192-198, 2005.

Li T, Ma G, Cai H, Price DL, Wong PC. "Nicastrin is required for assembly of presenilin/g-secretase complexes to mediate Notch Signaling, and for processing and trafficking of b-APP in mammals." J. Neuroscience 23: 3272-3277, 2003.

Wong PC, Cai H, Borchelt DR and Price DL. "Genetically Engineered Mouse Models of Neurodegenerative Diseases." Nature Neuroscience 5:633, 2002

Subramaniam JR, Lyons WE, Liu J, Bartinakas TB, Rothstein J, Price DL, Cleveland DW, Gitlin JD and Wong PC. "Mutant SOD1 causes motor neuron disease independent of copper chaperone-mediated copper loading." Nature Neuroscience 5:301, 2002.

Wong PC, Price DL, Cai H. "The brain's susceptibility to amyloid plaques." Science 293:1434, 2001.

Cai H, Wang Y, McCarthy D, Wen H, Borchelt DR, Price DL and Wong PC. "BACE1 is the major b-secretase for generation of Ab peptides by neurons." Nature Neuroscience 4: 233, 2001.

Chiang P-M, Ling J, Jeong YH, Price DL, Aja S and Wong PC: Deletion of TDP-43 down-regulates Tbc1d1, a gene linked to obesity, and alters body fat metabolism. Proc. Natl. Acad. Sci. USA 107: 16320-16324, 2010. PMID 20660762.

Shyam R, Ren Y, Lee J, Braunstein KE, Mao H-Q and Wong PC: Intraventricular delivery of siRNAs nanoparticles to the central nervous system. Molecular Therapy Nucleic Acids 4, e242, 2015 May 12.

Ling JP, Pletnikova O, Troncoso J and Wong PC: TDP-43 repression of non-conserved cryptic exons is compromised in ALS-FTD. Science 349:650-655, 2015. PMID 26250685.

Academic Affiliations & Courses

Graduate Program Affiliation

Cellular and Molecular Medicine Program

Neuroscience Graduate Program

Pathobiology

Activities & Honors

Honors

  • Zenith Fellows Award, Alzheimer’s Association, 2004
  • Teacher of the Year Award (Pathobiology Graduate Program, Department of Pathology, 2004
  • Cal Ripken/Lou Gehrig Fund for Neuromuscular Research, Johns Hopkins School of Medicine, 1997
  • Postdoctoral Fellowship, Muscular Dystrophy Association, 1990
  • Leadership and Excellence in Alzheimer's Disease (LEAD) Award, National Institute of Aging, 1994
  • CART Fund for Alzheimer’s disease research, Rotary CART, 2002

Memberships

  • New York Academy of Sciences, 2003
  • Society for Neuroscience, 1995

Professional Activities

  • Graduate Pathobiology Curriculum Committee, 2002
  • American Federation for Aging Research, 1999
  • Alzheimer’s Association, 1999
  • Ad hoc committee for Faculty Promotion, Department of Pathology, 2001
  • Admissions Committee, Cellular & Molecular Medicine, 2002
  • Advisory Board, Rodent Research, 2001
  • Chair, Division of Neuropathology, 2004
    Neurobiology of Disease Seminar Series Committee
  • Editorial board, Neuro-Signals, 2001
  • Molecular Pathology Seminar Series” Committee, Pathology Department, 1997
  • National Health and Medical Research Council, 1999
  • Operating Committee, Robert Packard Center for ALS Research at JHMI, 2003
  • Policy Committee, CMM, 2002
  • Research Advisory Committee, Division of Neuropathology, 2005
  • Research grant review panel, Canadian Institute of Health, 2006
  • Section Editor, Drugs Discovery Today: Disease Models, 2003
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