John Feng, Ph.D.
Assistant Professor of Pharmacology
Phone: (216) 368-3751
Fax: (216) 368-1300
E-mail: John.Feng@case.edu
Wood W-309A
Laboratory
Research Summary
Dissecting genetic mechanisms of dopamine neurotransmission-related human diseases, such as Parkinson’s Disease (PD), and screening for therapeutic drugs for these diseases.
PD is a major neurodegenerative disease without therapeutic medicine to prevent or reserve disease progression. PD is hallmarked by formation of filamentous inclusions (Lewy bodies or Lewy neurites), degeneration of dopaminergic (DAergic) neurons in the substantia nigra and disorder of extrapyramidal movement. Both environmental and inheritable factors critically contribute to PD pathogenesis. For example, neurotoxins, such as 6-oxyhydrodopamine, selectively kill DAergic and noradrenergic neurons, and produce behavioral symptoms mimicking PD in animals. Mutations of several human genes, such as α-synuclein, parkin, DJ-1 and PINK1, are associated with PD. Understanding how environmental and genetic factors interact with each other in PD pathogenesis holds the key to decipher the molecular mechanisms underlying PD and develop therapeutic strategies that prevent the origin, stop even reverse the progression of PD.
Recently, we established a human α-synuclein-expressing C. elegans PD model that recapitulates many essential pathological features of PD such as hαSyn amyloidosis, ageing progressive loss of DAergic neurons and adult-onset deficit in motor capability. With a collaboration with Drs. Kris Palczewski and Alex Moise, we found that α-synuclein aggregation disrupts dopamine homeostasis(Figure 1) and results in dopamine metabolism specific oxidative stress.
Our current focus is to dissect the role of dopamine metabolism specific oxidative stress in PD pathogenesis. Other research projects going on in my lab include 1) in vivo genetic and pharmacological screening for genes or chemicals preventing or enhancing α-synuclein mediated neurodegeneration and motor deficit; and 2) developing a novel in vivo Calcium imaging system. These projects are targeting to identify potential therapeutic drugs to treat PD or mapping functional neuronal circuits underlying behavior control, respectively.
Selected Publications:
Feng, Z., Li, W., Ward, A., Piggott, B., Larkspur, E., Sternberg, P. and Xu, S. A C. elegans model of nicotine-dependence: Regulation by TRP-Family channels. Cell (2006) 127 (3): 621-633. (Previewed research article)
Cronin C., Feng, Z. and Schafer W. Automated imaging of C. elegans behavior. Methods Mol. Biol. (2006) 351:241-251. (review).
Li, W., Feng, Z., Sternberg, P. and Xu, S. A C. elegans stretch-sensitive neuron revealed by a TRP family mechanotransduction channel homologue. Nature (2006) 440(7084): 684-687.
Feng, Z.*, Cronin C.*, Sternberg P. and Schafer, W.R. An imaging system for standardized quantitative analysis of C. elegans behavior. BMC Bioinformatics (2004) 5(1): 115
Baek, J.-H., Cosman, P., Feng, Z., Silver J., and Schafer W.R. Using machine vision to analyze and classify Caenorhabditis elegans behavioral phenotypes quantitatively. J. Neurosci. Meth. (2002) 118(1): 9-21.
Feng, Z., Butler, M., Alam, S., and Loh, S. On the nature of conformational openings: native- and unfolded-state hydrogen and thiol-disulfide exchange studies of Ferric aquomyoglobin. J. Mol. Biol. (2001) 314 (44): 153-166.
Feng, Z., Ha, J-H., and Loh, S. Identifying the site of initial tertiary structure disruption during apomyoglobin unfolding. Biochemistry (1999) 38 (1): 14433-14439.
Feng, Z., Aggeler, R., Haughton, M., and Capaldi, R. Conformational changes in the Escherichia coli ATP Synthase (ECF1F0) monitored by nucleotide-dependent differences in the maleimide labeling activity of Cys-87 of the gamma subunit in the mutant beta Glu-381/Ala.J. Biol. Chem. (1996) 271 (30): 17986-17989.