Qi Chen, Ph.D.
Assistant Professor
Blanchette Rockefeller Neurosciences Institute
E-mail: qchen@brni.org or qchen@hsc.wvu.edu
Phone: 304-293- 3962
Fax: 404-293-7536
Education:
Ph.D. University of Southern California
Research Interests and Goals:
Dr. Chen’s research goal is to better understand the mechanisms of brain function in aging and development, and to search for pharmacological strategies to promote cognitive health and to prevent neurodegenerative diseases and neuropsychiatric disorders such as Alzheimer’s disease, Parkinson’s disease, and schizophrenia. There are two ongoing projects which are currently under investigation:
Regulation of synaptic degeneration in Alzheimer’s disease
The early intervention is the key to protecting neurological function and for the detection and treatment of neurological diseases. Synaptic degeneration is a common feature leading to synapse loss in many neurological disorders including Alzheimer’s disease (AD). Synaptic loss is an early event in AD pathogenesis, even in patients with mild cognitive impairment (MCI), a prodromal state of AD, and is the best neurological correlate of the cognitive dysfunction in AD. If the mechanism underlying synaptic degeneration could be elucidated, then the pathway to develop the therapeutic treatment for preventing synaptic degeneration or to promote synaptic regeneration will become unraveled. We have established a mouse model to study the mechanisms underlying synaptic degeneration. The studies will reveal the intrinsic correlation between neuronal structure and function. By using this model and the in vitro cell system derived from this model, we plan to identify novel small molecules involved in the regulation of synaptic function and degeneration. Effects of these small molecules will be tested in AD and other neurological disease animal models.
Regulation of protein degradation in Alzheimer’s disease
Abnormal protein aggregates are associated with many neurodegenerative diseases. In AD, amyloid peptides are accumulated in senile plaques outside of cells while Tau proteins are accumulated as filamentous bodies shown in the inside of neurons. Amyloid plaque and Tau-associated neurofilamentous tangle are two major hallmarks of AD pathology. Understanding the causes of protein degradation defects which account for abnormal protein accumulation has significant impact to our knowledge in the course of AD pathogenesis. Our current studies are focused on elucidating the molecular pathways involved in the regulation of amyloid precursor protein (APP) degradation. The role of proteasomes in APP degradation is emphasized. This study will lead to finding novel targets for AD drug development.
Areas of Expertise:
Alzheimer’s disease; neurodegenerative diseases and animal models; molecular and cellular biology; biotechnology; neuropharmacology and neurotoxicity
Recent Publications:
Qi Chen, Charles Peto, Diane Shelton, Andrew Mizisin, Paul Sawchenko, and David Schubert: Loss of MOCA reveals a pathway leading to axonal degeneration. J. Neuroscience, 29(1): 118-130, 2009.
Federica Herrera, Qi Chen, Wolfgang Fischer, Pamela Maher, and David Schubert. Synaptojanin-1 plays a key role in astrogliogenesis: possible relevance for Down´s syndrome. Cell Death Diff. 16(6): 910-920, 2009.
Joe Burdo, Qi Chen, Nigel Calcutt, and David Schubert: The pathological interaction between diabetes and presymptomatic Alzheimer’s disease. Neurobiology of Aging, March 25, 2008.
Qiang Liu, Jie Zhang, Hua Zhu, Chuan Qin, Qi Chen, Baolu Zhao: Dissecting the signaling pathway of nicotine-mediated neuroprotection in a mouse Alzheimer’s disease model. FASEB J. 21(1): 61-73, 2007.
Jie Zhang, Qiang Liu, Qi Chen, Nian-Qing Liu, Fu-Liang Li, Zhong-Bing Lu, Chuan Qin, Hua Zhu, Huang Yu-Ying, Wei He, Bao-lu Zhao: Nicotine attenuates b-amyloid neurotoxicity by regulating metal homeostasis. FASEB J, 20(8): 1212-4, 2006.
L Diambra, LC Cintra, Q Chen, D Schubert, and L Da F Costa: Cell adhesion protein decreases cell motion: Statistical characterization of locomotion activity. Physica A 365, 481-490, 2006.
Zhang J, Mori A, Chen Q, Zhao B: Fermented papaya preparation attenuates beta-amyloid precursor protein: beta-amyloid-mediated copper neurotoxicity in beta-amyloid precursor protein and beta-amyloid precursor protein Swedish mutation overexpressing SH-SY5Y cells. Neuroscience 143: 63-72, 2006.
Qi Chen, Tsan-Ju Chen, Paul C. Letourneau, Luciano Da F. Costa, and David Schubert, Modifier of cell adhesion regulates N-cadherin-mediated cell-cell adhesion and neurite outgrowth. J. Neuroscience 25(2): 281-290, 2005.
Cynthia M. Grimsley, Jason M. Kinchen, Annie-Carole Tosello-Trampont, Enrico Brugnera, Lisa B. Haney, Mingjian Lu, Qi Chen, Doris Klingele, Michael O. Hengartner, and Kodi S. Ravichandran: DOCK180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration. J. Biol. Chem. 279(7): 6087-97 2004.
Haiyan Zeng, Qi Chen, Baolu Zhao: Genistein ameliorates beta-amyloid peptide(25-35)-induced hippocampal neuronal apoptosis. Free Radic Biol Med. 36(2): 180-8, 2004.
Qi Chen, Hideo Kimura, David Schubert: A Novel Mechanism for the Regulation of Amyloid Precursor Protein Metabolism. J. Cell Biology 158(1): 79-89, 2002.
Zhao, L., Chen, Q., and Brinton, R.D. Neuroprotective and Neurotrophic Efficacy of Phytoestrogens in Cultured Hippocampal Neurons, Experimental Biology and Medicine (Maywood) 227 (7): 509-519, 2002.
Qi Chen, David Schubert: Presenilin Interacting Proteins. Expert Reviews in Molecular Medicine, 22 August, http://www.expertreviews.org/02005008h.htm, 2002.
Qi Chen, Hirotaka Yoshida, David Schubert, Pamela Maher, Margaret Mallory, and Eliezer Masliah: Presenilin Binding Protein Is Associated with Neurofibrillary Alternations in Alzheimer’s Disease and Stimulates Tau Phosphorylation. Amer. J. Pathol. 159(5): 1597-1602, 2001.
Kumiko Ishige, Qi Chen, and David Schubert: The Activation of Dopamine D4 Receptors Inhibits Oxidative Stress Induced Nerve Cell Death. J. Neurosci., 21(16): 6069-6076, 2001.
Atsushi Kashiwa, Hirotaka Yoshida, Soon Lee, Toni PaladinoYuanbin Liu, Qi Chen, Richard Dargusch, David Schubert and Hideo Kimura: Isolation and Characterization of a Novel Presenilin Binding Protein. J. Neurochem. 75: 109-116, 2000.
Awards:
NIH Individual Service Grant Award, Principle Investigator, July 2003-June 2006.
The Neurobiology of Aging Training Grant, NIH, Post-doctoral Fellowship, July 2001-June 2003.
The Bundy Foundation Fellowship, Sept. 1999-2006.
The Pioneer Fund Fellowship, July 2000-July 2001.
Wang Kuang-Cheng Foundation Visiting Scholarship, Institute of Biophysics, Chinese Academy of Sciences, 1) May-June, 2001; 2) Sept.-Oct., 2003; 3) Aug.-Sept., 2006.