Yang Yang

Photo
Assistant Professor of Medicinal Chemistry and Molecular Pharmacology
Phone:
765-494-2926
Specialization: Pharmacogenomics, ion channels, induced pluripotent stem cells (iPSCs), neurological diseases

Education

B.S., B.A. (2005): Life Sciences/Sociology -- Shanghai University
Ph.D. (2011): Physiology/Biology -- Georgia State University
Postdoc. (2011-2014): Yale University School of Medicine
Associate Research Scientist (2014-2017): Yale University School of Medicine

Research

The focus of the research in Y-lab is on channelopathies of the nervous system. Channelopathies are diseases related to the dysfunction of ion channels, which are pore-forming membrane proteins that allow ions to pass through the cell membrane, controlling many indispensable functions of cells, including the generation of action potentials in neurons. Channelopathies, often resulting from inherited or de novo mutations, are responsible for a variety of human neurological diseases including chronic pain, epilepsy and autism.

Using state-of-the-art technologies (structural modeling, patch-clamp recordings, multi-electrode array recordings, live cell imaging, induced pluripotent stem cells, CRISPR-mediated genome-editing, and transgenic rodent models), Y-lab aims to understand how dysfunctions of ion channels contribute to neurological diseases, and to develop novel pharmacogenomic approaches targeting ion channels for disease intervention. 

Lab Members

Arryn Taylor Blaine (PULSe Graduate Student)
Muriel Eaton (Graduate Student)
Zhixiong Ma (Visiting Scholar)
Nazratan Naeem (Graduate Student)
Zhefu Que (Graduate Student)
Charlie C. Zhang (Lab Technician)
Jingliang Zhang (Visiting Scholar)

Representative Publications

1          Yang Y, Adi T, Effraim P, Chen L, Dib-Hajj SD, Waxman SG. Reverse pharmacogenomics: carbamazepine normalizes activation and attenuates thermal-induced hyperexcitability of sensory neurons due to Nav1.7 mutation I234T. British Journal of Pharmacology 2017, in press

2          Yang Y, Huang J, Mis MA, Estacion M, Macala L, Shah P, Schulman BR, Horton DB, Dib-Hajj SD, Waxman SG. Nav1.7-A1632G mutation from a family with inherited erythromelalgia: enhanced firing of dorsal root ganglia neurons evoked by thermal stimuli. Journal of Neuroscience 2016, 36:7511-22

3         Geha P, Yang Y, Estacion M, Schulman BR, Tokuno H, Apkarian AV, Dib-Hajj SD, Waxman SG. Pharmacotherapy for pain in a family with inherited erythromelalgia guided by genomic analysis and functional profiling. JAMA Neurology 2016, 73:659-67

(This paper is featured in Yale News: “personalized treatment for chronic pain closer to reality”.

4          Han C, Yang Y, de Greef BT, Hoeijmakers JG, Gerrits MM, Verhamme C, Qu J, Lauria G, Merkies IS, Faber CG, Dib-Hajj SD, Waxman SG. The Domain II S4-S5 linker in Nav1.9: a missense mutation enhances activation, impairs fast inactivation, and produces human painful neuropathy. NeuroMolecular Medicine 2015, 17:158-169

5          Huang J&, Yang Y&, Dib-Hajj SD, van Es M, Zhao P, Salomon J, Drenth JP, Waxman SG. Depolarized inactivation overcomes impaired activation to produce DRG neuron hyperexcitability in a Nav1.7 mutation in a patient with distal limb pain, Journal of Neuroscience 2014, 34(37):12328-40    (&, Equal contribution)

6          Yang Y*, Jin X, Jiang C. S-glutathionylation of ion channels: insights into the regulation of channel functions, thiol modification crosstalk, and mechanosensing, Antioxidants & Redox Signaling 2014, 20(6):937-51   (*, Corresponding author) 

7          Yang Y*, Konduru AS, Cui N, Yu L, Trower TC, Shi W, Shi Y, Jiang C. Acute exposure of methylglyoxal leads to activation of KATP channel expressed in HEK293 cells, Acta Pharmacologica Sinica (a Nature Publishing Group journal) 2014, 35:58-64  (*, Corresponding author)

8          Yang Y&, Vasylyev DV&, Dib-Hajj F, Veeramah KR, Hammer MF, Dib-Hajj SD, Waxman SG. Multi-state structural modeling and voltage-clamp analysis of epilepsy/autism mutation Kv10.2-R327H demonstrate the role of this residue in stabilizing the channel closed state, Journal of Neuroscience 2013, 33(42):16596-93  (&, Equal contribution)

9          Huang J, Yang Y, Zhao P, Gerrits MM, Hoeijmakers JG, Bekelaar K, Merkies IS, Faber CG, Dib-Hajj SD, Waxman SG. Small-fiber neuropathy Nav1.8 mutation shifts activation to hyperpolarized potentials and increases excitability of dorsal root ganglion neurons, Journal of Neuroscience 2013, 33(35):14087-14097

10       Dib-Hajj SD, Yang Y, Black JA, Waxman SG. The Nav1.7 sodium channel: from molecule to man, Nature Reviews Neuroscience 2013, 14(1): 49-62

11       Yang Y, Estacion M, Dib-Hajj SD, Waxman SG. Molecular architecture of a sodium channel S6 helix: radial tuning of the Nav1.7 activation gate, Journal of Biological Chemistry 2013, 288 (19): 13741-47

12       Yang Y, Dib-Hajj SD, Zhang J, Zhang Y, Tyrrell L, Estacion M, Waxman SG. Structural modeling and mutant cycle analysis predict pharmacoresponsiveness of a Nav1.7 mutant channel, Nature Communications 2012, 3:1186

(This paper is featured in ABC News: “New Hope for Man on Fire Syndrome”; Yale News: “In a world of chronic pain, individual treatment possible”; and Cover image of Chemical & Engineering News/C&EN: “Changing the Channel”)

13       Shields S, Ahn HS, Yang Y, Han C, Seal R, Wood JN, Waxman SG, Dib-Hajj SD. Nav1.8 expression is not restricted to nociceptors in mouse peripheral nervous system, PAIN 2012, 153(10):2017-30

14       Yang Y, Li S, Konduru AS, Zhang S, Trower TC, Shi W, Cui N, Yu L, Wang Y, Zhu D, Jiang C. Prolonged exposure to methylglyoxal causes disruption of vascular KATP channel by mRNA instability, American Journal of Physiology-Cell Physiology 2012, 303(10): C1045-54

15       Yang Y&, Shi W&, Chen X&, Cui N, Konduru AS, Shi Y, Trower TC, Jiang C. Molecular basis and structural insight of vascular KATP channel gating by S-glutathionylation, Journal of Biological Chemistry 2011, 286: 9298-307  (&, Equal contribution)

16       Yang Y, Shi W, Cui N, Wu Z, Jiang C. Oxidative stress inhibits KATP channel by S-glutathionylation, Journal of Biological Chemistry 2010, 285: 38641-8

17       Yang Y, Shi Y, Guo S, Zhang S, Cui N, Shi W, Zhu D, Jiang C. PKA-dependent activation of the vascular smooth muscle isoform of KATP channels by vasoactive intestinal polypeptide and its effect on relaxation of the mesenteric resistance artery, Biochimica et Biophysica Acta-Biomembranes 2008, 1778(1): 88-96

18       Yang Y, Qiu Y, Ren W, Gong J, Chen F. An identification of stem cell-resembling gene expression profiles in high-grade astrocytomas, Molecular Carcinogenesis 2008, 47: 893-903

19       Yang Y, Ren W, Chen F. Knockdown of Stat3 in C17.2 neural stem cells facilitates the generation of neurons: a possibility of transplantation with a low level of oncogene, NeuroReport 2006, 17: 235-8

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