Academic Staff > R.C.C. Chang

 

Raymond Chuen-Chung Chang ( 鄭傳忠 )
Associate Professor
B.Sc.(Hons), M.Phil. (CUHK), Dr. rer. BioHuman (Ph.D., Munich)

Department of Anatomy
L1-49. Laboratory Block
Faculty of Medicine Building
21 Sassoon Road, Hong Kong

Anatomy Office: (852) 3917-9127 (voice)
Anatomy Office: (852) 2817-0857 (fax)

E-mail: rccchang@hku.hk

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Background

Education / Training

  • BSc, The Chinese University of Hong Kong, Hong Kong (1987-1991)

  • MPhil, The Chinese University of Hong Kong, Hong Kong (1991-1993)

  • PhD, University of Munich (LMU), Munich, Germany (1994-1997)

  • Postdoctoral Fellow, National Institute of Environmental Health Sciences, National Institutes of Health, USA (1997-2000)

Personal Webpage

Other Affiliations

  • Management Committee and investigator, Research Centre of Heart, Brain, Hormone and Healthy Aging, LKS Faculty Medicine, HKU

  • Executive Management Committee and investigator, State Key Laboratory of Brain and Cognitive Sciences, HKU

  • Founder and Secretary, HKU Alzheimer’s Disease Research Network under Strategic Research Theme of Aging

  • Member, HKU Strategic Research Themes on Neuroscience, Ageing, Food Science and Drug Discovery

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Research

Research Interests

  • Alzheimer’s disease

  • Alzheimer pathology in the retina and glaucoma

  • Cognitive impairment in Parkinson’s disease

  • Neuroimmunology/neuroinflammation leading to Alzheimer’s disease

  • Herbal medicine to prevent neurodegeneration in Alzheimer’s disease

Research Description

Laboratory of Neurodegenerative Diseases

Mission of the Laboratory:
To elucidate the molecular mechanisms of neuronal death in aging-associated neurodegenerative diseases in order to develop neuroprotective agents

Focuses of Research:

  1. Molecular Mechanisms of Neuronal Degeneration (neuronal apoptosis, autophagy, synaptic degeneration & dysfunction of axonal transport) and Pharmacological Intervention including herbal medicine in Neurodegenerative Diseases

  2. Impact of Immune Responses in Neurological Disorders such as Alzheimer’s Disease and Glaucoma

  3. Elucidating the biological mechanisms of different risks factors leading to neurodegeneration and how to prevent different risk factors

Summary of Research:

  1. Molecular signaling of neuronal apoptosis, autophagy, synaptic degeneration and blockage of axonal transport.

      My research interest is to study the molecular signaling pathways of neuronal death in Alzheimer’s disease. It has been demonstrated that postmortem human brain section displays activated caspases, suggesting that neuronal apoptosis occurs in Alzheimer’s disease. We (Laboratory of Neurodegenerative Diseases) are the first to show that a novel double-stranded RNA-dependent protein kinase (PKR) is involved in β-amyloid peptide-induced neuronal apoptosis. Although it is originally named as double-stranded RNA-dependent protein kinase, recent findings have shown that PKR is a stress kinase for different stress signals. PKR is not simply involved in neuronal apoptosis; it also plays significant roles in the highly regulated degenerative processes. Apart from PKR, a major on-going project in our laboratory is to elucidate and map out how intracellular organelles such as endoplasmic reticulum (ER) and mitochondria are affected by low molecular weight β-amyloid (Aβ) peptides, resulting in either autophagy or neuronal apoptosis. In addition, we are now investigating the signaling events leading to autophagic neuronal death and synaptic degeneration. Understanding of the molecular signaling pathways will definitely pave a road for a better therapeutic strategy against neurodegenerative diseases.

  1. Cell-cell Interactions of glial cells on disease progression of neurodegeneration.

      Apart from the signaling pathways within neurons, cell-cell interaction between glia and neurons is also an important target for the therapy of neurodegenerative diseases. For example, how immune responses in the central nervous system affect the fate of neurons in various neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and glaucoma, is another thematic study in our group. Immune responses do not often occur in the brain, but only in the presence of potent immune stimulants or neuronal injuries. Innate immune components such as microglial cells are affected by normal neurotransmission and neurons. One of our research topics is to study how immune responses of glial cells in the eye affect the degeneration of retinal ganglion cells in glaucoma.

  1. Pharmacological targeting and drug discovery from herbal medicine for neurodegenerative diseases

      With all the above basic science studies, we are able to engage in applied research in searching for neuroprotective agents from Chinese medicine to natural products. Through the collaboration with colleagues in School of Biological Science and Department of Chemistry, we have identified several compounds that have high potentials to be neuroprotective agents. We are attempting to develop and commercialize some of the products into pharmaceutical market. We believe that prevention of neurodegeneration is better than treatment.

  1. Pathophysiological mechanisms of risk factors leading to aging-associated neurodegeneration

In recent years, we are particularly interested in understanding the pathophysiological mechanisms of different risk factors leading to neurodegenerative diseases. Epidemiological studies have shown that repeated episodes of depression can lead to neurodegeneration in the hippocampus. We have demonstrated that depression can be considered to be a type of neurodegeneration leading to atrophy of hippocampus. We are actively investigating how depression leads to neurodegeneration in Alzheimer’s disease. Apart from depression, we are also investigating high-fat diet, hypertension, cigarette smoking and systemic inflammation. All these studies will advance our knowledge of how different factors lead to aging-associated neurodegeneration, and how we can prevent neurodegeneration.

  1. Pathophysiological changes of retina to inform disease progression in the brainPathophysiological changes of retina to inform disease progression in the brain

      Our laboratory has been investigating pathological changes in the retina of Alzheimer’s disease. We could find accumulation of β-amyloid peptide and hyper-phosphorylation of tau protein in the retina of transgenic mice in Alzheimer’s disease. On the other hand, we could find similar pathology in glaucoma and aging-related macular degeneration. We propose that high level of β-amyloid peptide can be a pathological factor triggering neurodegeneration in different forms of glaucoma. We are investigating the similarity of their pathologies so that our eyes can be a window for monitoring disease progression and efficacy of therapeutic intervention. This is a novel concept in neurodegenerative disease research.

Research Grants

The laboratory has been supported by General Research Fund (GRF), RGC-NSFC Joint Research Scheme, and RGC-Procore France Joint Research Scheme by Research Grant Council of Hong Kong, American Health Assistant Foundation (now called BrightFocus Foundation, USA), The Glaucoma Foundation (USA), Azalea (1972) Foundation, Croucher Foundation, contract research by GlaxoSmithKline R&D and NeuroTech (HK) Limited, and generous donation from Ms. Kit-Wan CHOW.

Awards and Honors

  • Research Fellow Award for outstanding Hong Kong pre-doctoral student, German Academic Exchange Service (DAAD), Germany (1993-1997)

  • NATO Scholarship – Full sponsorship of the participation in NATO advanced course in flow cytometry, France (1995)

  • NIH Visiting Fellowship Award, NIH, U.S.A. (1997-2000)

  • Research Fellow Award for Research Excellence, National Institutes of Health, USA (1999)

  • Neuroscientist-Teacher Partner Award, Society for Neuroscience, USA (2006)

Editorship

Book Editor:

  1. Advanced Understanding of Neurodegenerative Diseases”, (2011) edited by Raymond Chuen-Chung CHANG. (by invitation to be editor) InTech Open Access Publisher, ISBN 978-953-307-485-6 (http://www.intechopen.com/books/show/title/advanced-understanding-of-neurodegenerative-diseases

  2. Neurodegenerative Diseases - Processes, Prevention, Protection and Monitoring”, (2011) edited by Raymond Chuen-Chung CHANG. (by invitation to be editor) InTech Open Access Publisher, ISBN 978-953-307-529-7 (http://www.intechopen.com/books/show/title/neurodegenerative-diseases-processes-prevention-protection-and-monitoring)

Editorial Boards:

  1. Section Chief Editor “Natural Medicine”, Journal of Neuroimmune Pharmacology

  2. Associate Editor, Journal of Alzheimer’s Disease

  3. American Journal of Alzheimer’s Disease and Related Dementia

  4. Advance in Alzheimer’s Disease

  5. Chinese Medicine

  6. Asia Journal of Neuroscience

  7. Journal of Brain and Behavioral Sciences

  8. Neural Regeneration Research

  9. Dataset Paper in Neuroscience

  10. Dataset Paper in Medicine (Ophthalmology)

  11. International Journal of Clinical and Experimental Medicine

  12. Anatomy & Physiology: Current Research

  13. The Open Enzyme Inhibition Journal

  14. World Journal of Methodology

  15. Journal of Neurology and Psychology

  16. Medicine

  17. "Medicine and Pharmacy" Board, InTech Open Access Publisher

Lab Personnel

  • Dr. Clara HL HUNG (Postdoc, Univ. Macau)

  • Dr. Olivia TW NG (Postdoc, Anesthesiology)

  • Mr. David CH POON (PhD student)

  • Miss Ginger TH WONG (PhD student, Psychiatry)

  • Miss Sally SY CHENG (PhD student)

  • Miss Ran YOU (PhD student)

  • Mr. Alan King LIU (PhD student, Imperial-HKU Joint PhD Program)

  • Miss Chunxia HUANG (PhD student, Anesthesiology)

  • Miss Yen LEUNG (MPhil student)

  • Ms. Carmen KM LOK (Lab Manager)

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Paper Highlight

  1. Ho YS, Yang X, Lau JCF, Hung CHL, Wuwongse S, Zhang Q, Wang JZ, Baum L, So KF and Chang RCC* (2012) Endoplasmic reticulum stress induces tau pathology and forms a vicious cycle: Implication in Alzheimer’s disease pathogenesis. J. Alz. Dis., 128, 839-854.
    [Correspondence author; Impact factor: 4.174 in the field of neuroscience; Rank of Journal: 64/251 (Top 25.5%) in the field of Neuroscience; Citation index: 9. In addition to the aggregation of the endoplasmic reticulum, this study demonstrates that endoplasmic reticulum stress induces phosphorylation of tau. In reverse, hyperphosphorylation of tau can trigger endoplasmic reticulum stress signaling responses. Therefore, two factors form vicious cycle to enforce neurodegeneration. The study has high implication to investigating the mechanisms of risk factors inducing neurodegeneration in Alzheimer’s disease.]

  2. Cheung YT, Zhang NQ, Hung CHL, Lai CSW, Yu MS, So KF, Chang RCC* (2011) Temporal Relationships of autophagy and neuronal apoptosis in low molecular weight β-amyloid peptide neurotoxicity. J. Cell. Mol. Med., 15, 244-257.
    [Correspondence author; Impact factor: 4.753; Rank of Journal: 19/121 (Top: 15.7%) in the field of Medicine: Research and Experimental; Citation index: 6. This is our second publication in this series of study to demonstrate that aggregation of the endoplasmic reticulum can induce autophagy at the first place and then result in neuronal apoptosis. From this study, we continue to investigate the molecular signaling of how autophagy is initiated by the aggregation of the endoplasmic reticulum.]

  3. Lai CSW, Preisler J, Baum L, Lee DHS, Ng HK, Hugon J, So KF, Chang RCC* (2009) Low molecular weight Aβ induces collapse of endoplasmic reticulum. Mol. Cell. Neurosci., 41, 32-43.
    [Correspondence author; Impact factor: 3.569; Rank of Journal: 78/231 (Top: 33.7%) in the field of Neuroscience; Citation index: 18. This is the first report showing that the toxin in Alzheimer’s disease, beta-amyloid peptide, induces collapse and aggregation of the endoplasmic reticulum. We, therefore, hypothesize that the endoplasmic reticulum instead of mitochondria is the key player in neurodegeneration triggered by beta-amyloid peptide. This is our foundation paper for next series of publications.]

  4. Chao J, Yu MS, Ho YS, Wang M, Chang RCC* (2008) Dietary oxyresveratrol prevents parkinsonian mimetic 6-hydroxydopamine neurotoxicity. Free Radic. Biol. Med., 45, 1019-1026.
    [Correspondence author; Impact factor: 6.081; Rank of Journal: 12/105 (Top: 11.4%) in the field of Endocrinology & Metabolism; Citation index: 57. This publication represents our effort in drug discovery program to protect neurons from food extract. This paper has high citation index because the neuroprotective effects of this food extract/supplement are comparable to its structural analog, resveratrol.]

Selected Publications

(from 98 publications of peer-reviewed books and papers since 2000, the year I joined HKU, h-index: 26 from Scopus, * = correspondence author)
Pubmed (for publications in Journals):
http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/44450828/?sort=date&direction=descending

Alzheimer’s Disease Research and Drug Discovery in this Area:

  1. Chang, R. C. C.*, Ho, Y. S., Wong, S., Gentleman, S. M., Ng, H. K. (2014) Neuropathology of cigarette smoking.  Acta Neuropathol., 127, 53-69.
     

  2. Wuwongse, S., Cheng, S. S. Y., Wong, G. T. H., Hung, C. H. L., Zhang, N. Q., Ho, Y. S., Law, A. C. K., Chang, R. C. C.* (2013) Effects of corticosterone and amyloid-beta on proteins essential for synaptic function: Implications for depression and Alzheimer’s disease. BBA- Mol. Basis Dis., 1832, 2245-2256.
     

  3. Ho, Y. S., Yang, X. F., Yeung, S. C., Chiu, K., Lau, C. F., Tsang, A. W. T., Mak, J. C. W., Chang, R. C. C.* (2012) Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats. PloS One, 7(5), e36752.
     

  4. Ho, Y. S., Yang, X. F., Lau, J. C. F., Hung, C. H. L., Wuwongse, S., Zhang, Q., Wang, J. Z., Baum, L., So, K. F. and Chang, R. C. C.* (2012) Endoplasmic reticulum stress induces tau pathology and forms a vicious cycle: Implication in Alzheimer’s disease pathogenesis. J. Alz. Dis., 28, 839-854.

Alzheimer pathology in the retina and glaucoma:

  1. Chiu, K., So, K. F., Chang, R. C. C.* (2013) Progressive neurodegeneration of retina in Alzheimer’s disease: Are -amyloid peptide and tau new pathological factors in glaucoma? In Shimon Rumelt edit: “Glaucoma – New Findings”. InTech Open Assess Publisher (Book Chapter), Chapter 8, 157-177. (ISBN 978-953-51-1064-4; http://dx.doi.org/10.5772/53428).
     

  2. Chiu, K., Chan, T. F., Wu, A., Leung, I. Y. P., So, K. F., Chang, R. C. C.* (2012) Neurodegeneration in the retina of mouse models of Alzheimer’s disease: what can we learn from the retina? AGE (Journal of American Aging Association), 34, 633-649.

Cognitive impairment in Parkinson’s Disease and Drug Discovery in this Area:

  1. Chao J, Leung Y, Wang M, Chang RCC* (2012) Nutraceuticals and their preventive or potential therapeutic value for Parkinson’s disease. Nutr. Rev., 70, 373-386.

Depression as risk factor of Alzheimer’s Diseases:

  1. Wong, G. T. S., Chang, R. C. C.*, Law, A. C. K. (2013) A breach in the scaffold: The possible role of cytoskeleton dysfunction in the pathogenesis of major depression. Ageing Res. Rev., 12, 67-75.
     

  2. Wuwongse, S., Chang, R. C. C.*, Law, A. C. K. (2010) The putative neurodegenerative links between depression and Alzheimer’s disease. Prog. Neurobiol., 91, 362-375.

 Neuroimmunology / Neuroinflammation leading to Alzheimer’s Diseases:

  1. Poon, D. C. H., Ho, Y. S., Chiu, K., Chang, R. C. C.* (2013) Cytokines: how important are they in mediating sickness? Neurosci. Biobehav. Rev., 37, 1-10.

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