Office Address: JSMBS 3148 (Downtown Campus)
Phone: (716) 829-2345
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.
(34) Y Ren, H Jiang, J Pu, L Li, J Wu, Y Yan, G Zhao, TJ Guttuso, B Zhang, J Feng (2021).
Molecular Features of Parkinson's Disease in Patient-Derived Midbrain Dopaminergic Neurons.
Movement Disorders doi: 10.1002/mds.28786. [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.
(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]
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.
(17) Y. Ren, X. Liu, S. Lesage, M. Cai, J. Pu, B. Zhang, A. Brice, J. Feng (2011).
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.
(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]
Ph.D. Biochemistry (1997), research advisor: James N. Ihle, Ph.D.
1986-1990: Nanjing University, Nanjing,
B.Sc. Biochemistry (1990)
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
Research advisor: Paul Greengard, Ph.D.
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,
07/12 - 06/21: Associate Editor (Stem Cell Biology section),
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]
This is the prelecture talk before the Michael J. Fox's Distinguished Speaker Lecture at UB.
Parkinson's Disease Research at UB, introduction to Michael J. Fox's speech at UB.