Jian
Feng, Ph.D.
UB Distinguished Professor
Department
of Physiology and Biophysics
School of Medicine &
Biomedical Sciences
State University of New York at
Buffalo
955 Main Street, Room 3148
Buffalo, NY 14203
Email: jianfeng@buffalo.edu
Phone: (716) 829-2345
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 4.6 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. We are using iPS cells and induced DA neurons to expand our studies to
idiopathic Parkinson's disease. The availability of human midbrain DA neurons
should significantly speed up the discovery of a cure for Parkinson's disease.
In our quest for making human nigral DA neurons, we come to realize that these special
cells are best made in vivo, due to their extraordinary axon arborization. We have discovered a method to convert human pluripotent stem cells (hPSCs)
from the primed state to the naive state. These naive hPSCs
are cultured in essentially the same condition used for maintaining mouse
embryonic stem cells. When naive hPSCs are
transferred to mouse blastocysts, they generate up to
4% of mature human cells of all three germ layers in mouse embryos at E17.5. A
large amount of enucleated human red blood cells are generated in mouse
embryos, showing a significant acceleration in the development of naive hPSCs in mouse embryos. This technology enables the
generation of human cells, tissues or even organs in animals. By studying how
human cells are made in chimeras, the long-term goal is to generate human cells
in an artificial system without the use of animals.
Selected
Publications from my laboratory: (click
here for complete bibliography) (Google
Scholar Citations)
(39)
Zhu B, Fisher E, Li L, Zhong P, Yan Z, Feng (2023)
PTBP2
attenuation facilitates fibroblast to neuron conversion by promoting
alternative splicing of neuronal genes.
Stem
Cell Reports 18:2268-2282 [PDF]
(38)
J Pu, L Lin, H Jiang, Z Hu,
H Li, Z Yan, B Zhang, J Feng (2023)
Parkin
Maintains Robust Pacemaking in Human iPSC-derived A9 Dopaminergic
Neurons.
Movement
Disorders 38:1273-1281 [PDF] [MDS
Podcast]
(37) H Li, H Jiang, H Li, L Li, Z Yan, J Feng (2022).
Generation
of human A9 dopaminergic pacemakers from induced pluripotent stem cells.
Molecular
Psychiatry 27:4407-4418. [PDF]
(36)
B Zhang and J Feng
(2022).
Mouse
embryonic stem cells require multiple amino acids.
Experimental
Biology and Medicine DOI:
10.1177/15353702221096059. [PDF]
(35)
E Fisher and J Feng
(2022).
RNA Splicing Regulators Play Critical Roles in Neurogenesis.
Wiley Interdisciplinary Reviews RNA e1728. doi: 10.1002/wrna.1728 [PDF]
(34)
Y Ren, H Jiang, J Pu, L Li,
J Wu, Y Yan, G Zhao, TJ Guttuso, B Zhang, J Feng (2022).
Molecular
Features of Parkinson's Disease in Patient-Derived
Midbrain Dopaminergic Neurons.
Movement
Disorders 37:70-79.
[PDF]
(33)
B Zhang, H Li, Z Hu, H Jiang, AB Stablewski,
BJ Marzullo, DA Yergeau, J Feng
(2021).
Generation of mouse-human chimeric
embryos.
Nature
Protocols 16:3954-3980 [PDF]
(32)
B Li, H Jiang, H Li, B Zhang, M Slaughter, Z Yan, J Feng (2021).
Direct
conversion of adult human retinal pigmented epithelium cells to neurons with
photoreceptor properties.
Experimental Biology and Medicine.
246:240-248 [PDF file]
(31)
J Feng
(2021)
Modeling the Pathophysiology
of Parkinson's Disease in Patient-specific Neurons.
Experimental Biology and Medicine.
246:298-304 [PDF file]
(30)
Z Hu, H Li, H Jiang, Y Ren,
X Yu, J Qiu, AB Stablewski,
B Zhang, MJ Buck, J Feng
(2020).
Transient Inhibition of mTOR
in Human Pluripotent Stem Cells Enables Robust
Formation of Mouse-Human Chimeric Embryos.
Science
Advances 6: eaaz0298. [PDF file] [Press Coverage] [Altmetric]
(29)
H Li, Z Hu, H Jiang, J Pu,
I Selli, J Qiu, B Zhang, J Feng
(2020).
TET1
Deficiency Impairs Morphogen-free Differentiation of
Human Embryonic Stem Cells to Neuroectoderm.
Scientific
Reports 10:10343 [PDF file]
(28)
H Li, H Jiang, X Yin, JE Bard, B Zhang, J
Feng (2019).
Attenuation
of PRRX2 and HEY2 enables efficient conversion of adult human skin fibroblasts
to neurons.
Biochem Biophys Res Commun.
516:765-769. [PDF
file]
(27)
H Li, H Jiang, B Zhang, J Feng (2018).
Modeling Parkinson's Disease Using Patient-specific
Induced Pluripotent Stem Cells.
Journal
of Parkinson's Disease
8:479-493. [PDF file]
(26)
P Zhong, Z Hu, H Jiang, Z
Yan, J Feng
(2017).
Dopamine
Induces Oscillatory Activities in Human Midbrain Neurons with Parkin Mutations.
Cell
Reports 19:1033-1044. [PDF file]
(25)
Z Xu, X
Induced
dopaminergic neurons: A new promise for Parkinson's
disease. Redox Biology 11:606-612. [PDF file]
(24)
J Feng
(2016).
Kinetic
Barriers in Transdifferentiation.
Cell
Cycle, 15:1019-1020 [PDF file]
(23)
Z Xu, H Jiang, P Zhong, Z
Yan, S Chen, J Feng
(2016). Direct Conversion of Human Fibroblasts to Induced Serotonergic
Neurons. Molecular Psychiatry, 21:62-70. [PDF file]
(22)
H Jiang, Z Xu, P Zhong, Y Ren, G Liang, HA Schilling, Z Hu,
Y Zhang, X Wang, S Chen, Z Yan, J Feng (2015). Cell Cycle and p53 Gate the Direct
Conversion of Human Fibroblasts to Dopaminergic
Neurons. Nature Communications, 6: 10100. [PDF file]
(21)
Z Hu, J Pu, H Jiang, P Zhong, J Qiu, F Li, X Wang, B
Zhang, Z Yan, J Feng
(2015).
Generation
of Naivetropic Induced Pluripotent
Stem Cells from Parkinson's Disease Patients for High Efficiency Genetic
Manipulation and Disease Modeling.
Stem
Cells and Development.
24:2591-2604. [PDF file]
(20) J Pu, D Frescas, B
Zhang, J Feng (2015).
Utilization
of TALEN and CRISPR/Cas9 technologies for gene targeting and modification. Experimental
Biology and Medicine 240:1065-1070. [PDF file]
(19) Y Ren, H Jiang, Z Hu, K Fan, J Wang, S Janoschka, X
Wang, S Ge, J Feng (2015). Parkin Mutations
Reduce the Complexity of Neuronal Processes in iPSC-derived
Human Neurons. Stem Cells, 33:68-78. [PDF file]
(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
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. [PDF file]
(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), research advisor: James N.
Ihle, Ph.D.
1986-1990: Nanjing University, Nanjing,
China.
B.Sc. Biochemistry (1990)
Academic Appointments:
2010-Present:
Director
Induced
Pluripotent Stem Cell Facility
Western New York Stem Cell Culture and
2000-Present:
Professor (2010-), Associate Professor (2005-2010), Assistant Professor
(2000-2005)
Department of Physiology and Biophysics
1997-2000:
Postdoctoral Associate
Laboratory of Molecular and Cellular Neuroscience
The
Research advisor: Paul
Greengard, Ph.D.
Awards:
University at Buffalo
Exceptional Scholars - Sustained Achievement Award (10/17)
Top 100 Principle
Investigators, State University of New York at Buffalo (10/05).
Visionary Inventor Award,
Promising Inventor Award,
Top 100 Federal Grantee,
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,
Alma and Hal Reagan Fellowship in Cancer Research,
Univ. of
Membership:
Parkinson's
Disease iPS Cell Line
Consortium
International
Society for Stem Cell Research
Editorial Board:
07/12 - 06/21: Associate Editor (Stem Cell Biology
section),
Experimental
Biology and Medicine
Commentary:
Jian Feng. Entropy illustrates the flexibility of
Chinese. Nature 410: 1021 (2001) [PDF file]
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.