Jian
Feng , Ph.D.
Professor
Department of Physiology and
Biophysics
School of Medicine &
Biomedical Sciences
State University of New York at
Buffalo
124 Sherman Hall
Buffalo, NY 14214
Email: jianfeng@buffalo.edu
Office Address: BRB 549 (South Campus)
Tel: (716) 829-2345, Fax: (716) 829-2699
Research:
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.
Publications
from my laboratory:
(18) H Jiang, Y Ren, EY Yuen, P Zhong, M Ghaedi, Z Hu,
G Azabdaftari, K Nakaso, Z Yan, J Feng (2012).
Parkin Controls Dopamine Utilization in Human Midbrain
Dopaminergic Neurons Derived from Induced Pluripotent Stem Cells.
Nature Communications 3:668. [PDF file] [Press Coverage]
(17) Y. Ren, X. Liu, S. Lesage, M. Cai, J. Pu, B. Zhang, A.
Brice, J. Feng (2011).
The Normal Parkin Sequence.
Movement Disorders PMID: 22095769. [PDF
file]
(16)
Y. Ren, H. Jiang, D. Ma, K. Nakaso, J.
Feng (2011).
Parkin
Degrades Estrogen Related Receptors to Limit the Expression of Monoamine
Oxidases.
Hum.
Mol. Genet. 20:1074-1083. [PDF file]
(15) H. Jiang, D. Cheng, W. Liu, J. Peng, J. Feng (2010).
Protein Kinase C Inhibits Autophagy and Phosphorylates
LC3.
Biochem Biophys Res Commun. 395:471-476. [PDF file]
(14)
Y. Ren, H. Jiang, F. Yang, K. Nakaso, and J.
Feng (2009).
Parkin
protects dopaminergic neurons against microtubule-depolymerizing toxins by
attenuating MAP kinase activation.
J.
Biol. Chem. 284:4009-4017. [PDF file]
(13)
Q. Jiang, Y. Ren, and J. Feng
(2008).
Direct
Binding with Histone Deacetylase 6 Mediates the Reversible Recruitment of
Parkin to the Centrosome.
J.
Neurosci. 28:12993–13002. [PDF file]
(12)
Y. Ren and J. Feng (2007).
Rotenone
Selectively Kills Serotonergic Neurons through a Microtubule-dependent
Mechanism.
J.
Neurochem. 103:303-311. [PDF file]
(11) J. Feng (2006).
Microtubule:
a Common Target for Parkin and Parkinson’s Disease Toxins.
Neuroscientist. 12:469-476. [PD
(10)
Q. Jiang, Z. Yan, and J. Feng
(2006).
Neurotrophic
factors stabilize microtubules and protect against rotenone toxicity on
dopaminergic neurons.
J.
Biol. Chem. 281:29391-29400. [PDF file]
(9)
H. Jiang, Q. Jiang, W. Liu and J. Feng (2006).
Parkin
Suppresses the Expression of Monoamine Oxidases.
J.
Biol. Chem. 281:8591-8599. [PDF file]
(8)
Q. Jiang, Z. Yan, and J. Feng
(2006).
Activation
of Group III Metabotropic Glutamate Receptors Attenuates Rotenone Toxicity on
Dopaminergic Neurons through a Microtubule-dependent Mechanism.
J.
Neurosci. 26:4318-4328. [PDF file]
(7)
Y. Ren, W. Liu, H. Jiang, Q. Jiang, and J.
Feng (2005).
Selective
Vulnerability of Dopaminergic Neurons to Microtubule Depolymerization.
J.
Biol. Chem. 280:34105-34112. [PDF file] [Media Coverage]
(6)
F. Yang, Q. Jiang, J. Zhao, Y. Ren, M.D. Sutton and J. Feng (2005).
Parkin
Stabilizes Microtubules through Strong Binding Mediated by Three Independent
Domains.
J.
Biol. Chem. 280:17154-17162.
[PDF file]
(5)
H. Jiang, Q. Jiang and J. Feng
(2004).
Parkin
Increases Dopamine Uptake by Enhancing the Cell Surface Expression of Dopamine
Transporter.
J.
Biol. Chem. 279:54380-54386. [PDF
file]
(4)
H. Jiang, Y. Ren, J. Zhao and J. Feng
(2004).
Parkin
protects human dopaminergic neuroblastoma cells against dopamine-induced
apoptosis.
Hum.
Mol. Genet. 13: 1745-1754. [PDF file]
(3) J. Feng (2003).
Genetic
factors in Parkinson’s disease and potential therapeutic targets.
Curr.
Neuropharmacol. 1: 301-313. [PDF file]
(2) J.
Zhao, Y. Ren, Q. Jiang and J. Feng (2003).
Parkin
is recruited to the centrosome in response to inhibition of proteasomes.
J.
Cell Sci. 116: 4011-4019. [PDF file]
(1)
Y. Ren, J. Zhao and J. Feng (2003).
Parkin binds to a/β tubulin and
increases their ubiquitination and degradation.
J. Neurosci. 23: 3316-3324. [PDF file]
Biographical Information:
Education:
1993-1997:
Ph.D. Biochemistry (1997),
1986-1990:
B.Sc. Biochemistry (1990)
Academic Appointments:
2010-Present: Director
Induced
Pluripotent Stem Cell Facility
Western New York Stem Cell Culture and Analysis Center
State University of New York at Buffalo,
Buffalo, NY
2000-Present: Professor (2010-), Associate Professor
(2005-2010), Assistant Professor (2000-2005)
Department
of Physiology and Biophysics
School
of Medicine and Biomedical Sciences
State
University of New York at Buffalo, Buffalo, NY.
1997-2000: Postdoctoral Associate
Laboratory of Molecular and Cellular Neuroscience
The
Rockefeller University, New York, NY.
Research
advisor: Paul
Greengard, Ph.D.
Awards:
·
Top 100 Principle Investigators,
· Visionary Inventor Award, State University of New York at Buffalo
(5/05).
· Promising Inventor Award, State University of New York (11/04).
· Top 100 Federal Grantee, State University of New York at Buffalo
(11/02)
· Young Investigator Achievement Award, SUNY-Buffalo (5/02).
· Theodore and Vada Stanley Foundation Research Award (8/98-7/00).
· Ralph R. Braund Young Investigator Award in Cancer Research, Univ. of
Tennessee and Memphis Cancer Society (4/97).
· Alma and Hal Reagan Fellowship in Cancer Research, Univ. of Tennessee
(7/95 - 6/97).
Membership:
Parkinson’s
Disease iPS Cell Line Consortium
American
Society of Cell Biology
American Society
for Pharmacology and Experimental Therapeutics
International
Society for Stem Cell Research
Commentary:
Jian Feng. Embryonic Stem Cells: Don’t let litigation
put research off limits. Nature 467: 271 (2010) [PDF
file]
Public Lecture:
Jian Feng. Finding
a cure for Parkinson’s disease. Oct.
19, 2011. [video]
This is the prelecture talk
before the Michael J. Fox's Distinguished Speaker Lecture at UB.
Documentary:
Parkinson's Disease Research
at UB, introduction to Michael J. Fox's speech at UB.
Profiles
elsewhere:
Michael
J. Fox Foundation for Parkinson’s Disease Research