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Jian                           Feng

Jian Feng PhD

Department of Physiology and Biophysics

Professor

Specialty/Research Focus

Apoptosis and cell death; Cytoskeleton and cell motility; Gene Expression; Molecular and Cellular Biology; Molecular genetics; Neurobiology; Neurodegenerative disorders; Neurology; Pathophysiology; Protein Folding; Signal Transduction; Toxicology and Xenobiotics; Transcription and Translation

 
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Professional Summary:

My research is aimed at finding the cause and a cure for Parkinson’s disease.

Parkinson’s disease (PD) is defined by a characteristic set of locomotor symptoms (rest tremor, rigidity, bradykinesia and postural instability) that are believed to be caused by the selective loss of dopaminergic (DA) neurons in substantia nigra. The persistent difficulties in using animals to model this human disease suggest that human nigral dopaminergic neurons have certain vulnerabilities that are unique to our species.

One of our unique features is the large size of the human brain (1350 grams on average) relative to the body. A single nigral dopaminergic neuron in a rat brain (2 grams) has a massive axon arbor with a total length of 45 centimeters. Assuming that all mammalian species share a similar brain wiring plan, we can estimate (using the cube root of brain weight) that a single human nigral dopaminergic neuron may have an axon with gigantic arborization that totals 4 meters.

Another unique feature of our species is our strictly bipedal movement, which is affected by Parkinson’s disease, in contrast to the quadrupedal movement of almost all other mammalian species. The much more unstable bipedal movement may require more dopamine, which supports the neural computation necessary for movement.

The landmark discovery of human induced pluripotent stem cells (iPSC) made it possible to generate patient-specific human midbrain dopaminergic neurons to study Parkinson’s disease. A key problem for dopaminergic neurons is the duality of dopamine as a signal required for neural computation and a toxin as its oxidation produces free radicals. Our study using iPSC-derived midbrain dopaminergic neurons from PD patients with parkin mutations and normal subjects shows that parkin sustains this necessary duality by maintaining the precision of the signal while suppressing the toxicity. Mutations of parkin cause increased spontaneous release of dopamine and reduced dopamine uptake, thereby disrupting the precision of dopaminergic transmission. On the other hand, transcription of monoamine oxidase is greatly increased when parkin is mutated. This markedly increases dopamine oxidation and oxidative stress. These phenomena have not been seen in parkin knockout mice, suggesting the usefulness of parkin-deficient iPSC-derived midbrain DA neurons as a cellular model for Parkinson’s disease.

Currently, we are using iPS cells and induced DA neurons to expand our studies on parkin to idiopathic Parkinson’s disease. We are also utilizing the molecular targets identified in our studies to find small-molecule compounds that can mimic the beneficial functions of parkin. The availability of human midbrain DA neurons should significantly speed up the discovery of a cure for Parkinson’s disease.

Education and Training:
  • PhD, Biochemistry, University of Tennessee (1997)
  • BS, Biochemistry, Nanjing University (1990)
Employment:
  • Professor, State University of New York at Buffalo (2010-present)
  • Associate Professor, Physiology and Biophysics, State University of New York at Buffalo (2005–2010)
  • Assistant Professor, Physiology and Biophysics, State University of New York at Buffalo (2000–2005)
  • Postdoctoral Research Associate, Laboratory of Molecular and Cellular Neuroscience, Rockefeller University (1997–2000)

Grants and Sponsored Research:
  • January 2009–December 2013
    Cellular Functions of Parkin
    NIH/NINDS
    Role: Principal Investigator
    $1,733,595

Journal Articles:
  • Liu W, Dou F, Feng J, Yan Z. RACK1 is involved in β-amyloid impairment of muscarinic regulation of GABAergic transmission. Neurobiol Aging. 2011; 32(10).
  • Ren Y, Jiang H, Ma D, Nakaso K, Feng J. Parkin degrades estrogen-related receptors to limit the expression of monoamine oxidases. Hum Mol Genet. 2011; 20(6).
  • Yuen EY, Liu W, Karatsoreos IN, Ren Y, McEwen BS, Yan Z, Feng J. Mechanisms for acute stress-induced enhancement of glutamatergic transmission and working memory.. Molecular Psychiatry. 2011; 16(2).
  • H. Jiang, D. Cheng, W. Liu, J. Peng, J. Feng. Protein Kinase C Inhibits Autophagy and Phosphorylates LC3 Biochem Biophys Res Commun. 2010; 395(4).
  • B. Porton, R.M. Rodriguiz, L.E. Phillips, J.W. Gilbert, J. Feng, P. Greengard, H.T. Kao, W.C. Wetsel. Mice lacking synapsin III show abnormalities in explicit memory and conditioned fear. Genes Brain Behav. 2010; 9(3).
  • Roth JA Singleton S Feng J Garrick M Paradkar P. Parkin regulates metal transport via proteasomal degradation of the 1B isoforms of divalent metal transporter 1 Journal of Neurochemistry. 2010; 113.
  • Yuen EY, Liu W, Karatsoreos IN, Feng J, McEwen BS, Yan Z. Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory. Proc Natl Acad Sci U S A. 2009; 106(33).
  • Ren Y, Jiang H, Yang F, Nakaso K, Feng J. Parkin protects dopaminergic neurons against microtubule-depolymerizing toxins by attenuating microtubule-associated protein kinase activation. J Biol Chem. 2009; 284(6).
  • Jiang Q, Ren Y, Feng J. Direct binding with histone deacetylase 6 mediates the reversible recruitment of parkin to the centrosome. J Neurosci. 2008; 28(48).
  • Kao HT, Li P, Chao HM, Janoschka S, Pham K, Feng J, Mcewen BS, Greengard P, Pieribone VA, Porton B. Early involvement of synapsin III in neural progenitor cell development in the adult hippocampus. J Comp Neurol. 2008; 507(6).
  • Madden MM, Song W, Martell PG, Ren Y, Feng J, Lin Q. Substrate properties of ubiquitin carboxyl-terminally derived peptide probes for protein ubiquitination. Biochemistry. 2008; 47(12).
  • Chen G, Chen P, Tan H, Ma D, Dou F, Feng J, Yan Z. Regulation of the NMDA receptor-mediated synaptic response by acetylcholinesterase inhibitors and its impairment in an animal model of Alzheimer’s disease.. Neurobiol. Aging. 2008; 29.
  • Feng J. Microtubule: a common target for parkin and Parkinson‘s disease toxins. Neuroscientist. 2006; 12(6).
  • Jiang Q, Yan Z, Feng J. Neurotrophic factors protect against rotenone toxicity on dopaminergic neurons through a microtubule-dependent mechanism. J Biol Chem. 2006; 281.
  • Jiang Q, Yan Z, Feng J. Activation of group III metabotropic glutamate receptors attenuates rotenone toxicity on dopaminergic neurons through a microtubule-dependent mechanism. J Neurosci. 2006; 26.
  • Jiang H, Jiang Q, Liu W, Feng J. Parkin suppresses the expression of monoamine oxidases. J Biol Chem. 2006; 281(13).
  • Yang F, Jiang Q, Zhao J, Ren Y, Sutton MD, Feng J. Parkin stabilizes microtubules through strong binding mediated by three independent domains. J Biol Chem. 2005; 280(17).
  • Jiang H, Jiang Q, Feng J. Parkin increases dopamine uptake by enhancing the cell surface expression of dopamine transporter. J Biol Chem. 2004; 279(52).
  • Zhao J, Ren Y, Jiang Q, Feng J. Parkin is recruited to the centrosome in response to inhibition of proteasomes. J Cell Sci. 2003; 116(Pt 19).
  • Zhong P, Gu Z, Wang X, Jiang H, Feng J, Yan Z. Impaired modulation of GABAergic transmission by muscarinic receptors in a mouse transgenic model of Alzheimer's disease.. J Biol Chem. 2003; 278(29).
  • Ren Y, Zhao J, Feng J. Parkin binds to alpha/beta tubulin and increases their ubiquitination and degradation.. J Neurosci. 2003; 23(8).
  • Ma XH, Zhong P, Gu Z, Feng J, Yan Z. Muscarinic potentiation of GABA(A) receptor currents is gated by insulin signaling in the prefrontal cortex.. J Neurosci. 2003; 23(4).
  • Pieribone VA, Porton B, Rendon B, Feng J, Greengard P, Kao HT. Expression of synapsin III in nerve terminals and neurogenic regions of the adult brain.. J Comp Neurol. 2002; 454(2).
  • Carpino N, Kobayashi R, Zang H, Takahashi Y, Jou ST, Feng J, Nakajima H, Ihle JN. Identification, cDNA cloning, and targeted deletion of p70, a novel, ubiquitously expressed SH3 domain-containing protein.. Mol Cell Biol. 2002; 22(21).
  • Feng J, Chi P, Blanpied TA, Xu Y, Magarinos AM, Ferreira A, Takahashi RH, Kao HT, McEwen BS, Ryan TA, Augustine GJ, Greengard P. Regulation of neurotransmitter release by synapsin III.. J Neurosci. 2002; 22(11).
  • Cai X, Flores-Hernandez J, Feng J, Yan Z. Activity-dependent bidirectional regulation of GABA(A) receptor channels by the 5-HT(4) receptor-mediated signalling in rat prefrontal cortical pyramidal neurons.. J Physiol. 2002; 540(Pt 3).
  • Feng J, Cai X, Zhao J, Yan Z. Serotonin receptors modulate GABA(A) receptor channels through activation of anchored protein kinase C in prefrontal cortical neurons.. J Neurosci. 2001; 21(17).
  • Stafstrom-Davis CA, Ouimet CC, Feng J, Allen PB, Greengard P, Houpt TA. Impaired conditioned taste aversion learning in spinophilin knockout mice.. Learn Mem. 2001; 8(5).
  • Feng J, Yan Z, Ferreira A, Tomizawa K, Liauw JA, Zhuo M, Allen PB, Ouimet CC, Greengard P. Spinophilin regulates the formation and function of dendritic spines.. Proc Natl Acad Sci U S A. 2000; 97(16).
  • Wang D, Feng J, Wen R, Marine JC, Sangster MY, Parganas E, Hoffmeyer A, Jackson CW, Cleveland JL, Murray PJ, Ihle JN. Phospholipase Cgamma2 is essential in the functions of B cell and several Fc receptors.. Immunity. 2000; 13(1).
  • Ferreira A, Kao HT, Feng J, Rapoport M, Greengard P. Synapsin III: developmental expression, subcellular localization, and role in axon formation.. J Neurosci. 2000; 20(10).
  • Wang D, Moriggl R, Stravopodis D, Carpino N, Marine JC, Teglund S, Feng J, Ihle JN. A small amphipathic alpha-helical region is required for transcriptional activities and proteasome-dependent turnover of the tyrosine-phosphorylated Stat5.. EMBO J. 2000; 19(3).
  • Yan Z, Feng J, Fienberg AA, Greengard P. D(2) dopamine receptors induce mitogen-activated protein kinase and cAMP response element-binding protein phosphorylation in neurons.. Proc Natl Acad Sci U S A. 1999; 96(20).
  • Yan Z, Hsieh-Wilson L, Feng J, Tomizawa K, Allen PB, Fienberg AA, Nairn AC, Greengard P. Protein phosphatase 1 modulation of neostriatal AMPA channels: regulation by DARPP-32 and spinophilin.. Nat Neurosci. 1999; 2(1).
  • Ihle JN, Thierfelder W, Teglund S, Stravapodis D, Wang D, Feng J, Parganas E. Signaling by the cytokine receptor superfamily.. Ann N Y Acad Sci. 1998; 865.
  • Ihle JN, Stravapodis D, Parganas E, Thierfelder W, Feng J, Wang D, Teglund S. The roles of Jaks and Stats in cytokine signaling.. Cancer J Sci Am. 1998; 4 Sup.
  • Quelle FW, Wang J, Feng J, Wang D, Cleveland JL, Ihle JN, Zambetti GP. Cytokine rescue of p53-dependent apoptosis and cell cycle arrest is mediated by distinct Jak kinase signaling pathways.. Genes Dev. 1998; 12(8).
  • Kao HT, Porton B, Czernik AJ, Feng J, Yiu G, Häring M, Benfenati F, Greengard P. A third member of the synapsin gene family.. Proc Natl Acad Sci U S A. 1998; 95(8).
  • Shimoda K, Feng J, Murakami H, Nagata S, Watling D, Rogers NC, Stark GR, Kerr IM, Ihle JN. Jak1 plays an essential role for receptor phosphorylation and Stat activation in response to granulocyte colony-stimulating factor.. Blood. 1997; 90(2).
  • Feng J, Witthuhn BA, Matsuda T, Kohlhuber F, Kerr IM, Ihle JN. Activation of Jak2 catalytic activity requires phosphorylation of Y1007 in the kinase activation loop.. Mol Cell Biol. 1997; 17(5).
  • Kohlhuber F, Rogers NC, Watling D, Feng J, Guschin D, Briscoe J, Witthuhn BA, Kotenko SV, Pestka S, Stark GR, Ihle JN, Kerr IM. A JAK1/JAK2 chimera can sustain alpha and gamma interferon responses.. Mol Cell Biol. 1997; 17(2).
See All (41 Total) >
Abstracts:


Clinical Specialties:
Clinical Offices:
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Contact Information

549 Biomedical Research Building
Buffalo, NY 14214
Phone: (716) 829-2345
Fax: 716-829-2699
Email: jianfeng@buffalo.edu


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