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James J. Chou
James J. Chou in 2019
Born (1970-08-26) August 26, 1970 (age 54)
Shanghai, China
NationalityAmerican

James J. Chou (周界文) is a Chinese American scientist and Professor of Biological Chemistry and Molecular Pharmacology at the Harvard Medical School. He is known for pioneering the use of Nuclear Magnetic Resonance (NMR) Spectroscopy to reveal the structural details of the membrane regions (transmembrane and membrane-proximal) of cell surface proteins, particularly those of immune receptors and viral membrane proteins.

Biography

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James J. Chou was born in Shanghai, China, and immigrated to the United States to join his parents in 1984. He obtained his B.S. in physics from University of Michigan at Ann Arbor. He then received Ph.D. in Biophysics from the Harvard University, where he studied protein NMR spectroscopy under the supervision of Gerhard Wagner. Dr. Chou furthered his training in NMR by doing a postdoctoral fellowship in the lab of Adriaan Bax at the US National Institutes of Health. Dr. Chou joined the faculty at Harvard Medical School in 2003 and moved up the rank to tenured full professor in 2012.

Dr. Chou currently resides in Belmont, Massachusetts. His father, Kuo-Chen Chou, is a well-known computational biophysicist who founded the Gordon Life Science Institute. His mother, Wei-Zhu Zhong, is also a scientist who worked at Upjohn, Pharmacia, and Pfizer.

Scientific contributions

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As a graduate student in Gerhard Wagner’s Lab at Harvard Medical School, he investigated the solution structures and mechanism of proteins involved in programmed cell death including the CARD (caspase recruitment domain) [1] and the BID. [2]

In his postdoctoral study with Adriaan Bax, Dr. Chou applied NMR residual dipolar coupling (RDC) methods to reveal the conformational dynamics of the EF-hands of the calcium binding protein Calmodulin. [3] He also combined the RDC application and bicelles to investigate small membrane protein domains in near lipid bilayer environment. [4]

As an independent investigator, Dr. Chou continued NMR studies of membrane proteins to fill the knowledge gap in the transmembrane and membrane-proximal regions of several immune receptors and viral membrane proteins. The membrane regions of cell surface proteins are difficult targets for X-ray crystallography because they are generally very hydrophobic and often dynamic; they are also too small for the state-of-the-art cryogenic electron microscopy. The NMR-based protocols [5] pioneered by Dr. Chou constitute a general means of revealing these “blind spots” in structural biology. Using these methods, Chou made several unexpected discoveries such as the critical roles of the membrane regions in immune receptor clustering and activation [6] [7] [8] [9] [10] and in viral membrane fusion protein assembly. [11] [12] [13] In addition to the above major scientific contributions, some of his earlier significant discoveries include structure and mechanism of viral ion channels [14] [15] [16] [17] [18] and dynamic nature of membrane channels and carriers. [19] [20] [21]

Awards and Fellowships

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  • Harvard Biophysics Fellowship (1994–1996).[22]
  • NIH IRTA Postdoctoral Fellowship (1999–2001).
  • Glaxo-Smith Life Science Fellow (2003–2005).[23]
  • The Smith Family New Investigator Award (2005).[24]
  • The Alexander and Margaret Stewart Trust Award (2005).[25]
  • PEW Scholar in the Biomedical Sciences (2005).[26]
  • Giovanni Armenise-Harvard Junior Faculty Award (2006).[27]
  • Genzyme Outstanding Achievement in Biomedical Science Award (2009).

References

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  1. ^ Chou, JJ; Matsuo, H; Duan, H; Wagner, G (1998). "Solution Structure of the RAIDD CARD Domain and Model for CARD/CARD Interaction in Caspase-2 and Caspase-9 Recruitment". Cell. 94 (2): 171–80. doi:10.1016/s0092-8674(00)81417-8. PMID 9695946.
  2. ^ Chou, JJ; Li, H; Salvessen, GS; Yuan, J; Wagner, G (1999). "Solution Structure of BID, an Intracellular Amplifier of Apoptotic Signaling". Cell. 96 (5): 615–24. doi:10.1016/s0092-8674(00)80572-3. PMID 10089877.
  3. ^ Chou, JJ; Li, S; Klee, CB; Bax, A (2001). "Solution structure of Ca2+–calmodulin reveals flexible hand-like properties of its domains". Nature Structural Biology. 8 (11): 990–7. doi:10.1038/nsb1101-990. PMID 11685248. S2CID 4665648.
  4. ^ Chou, JJ; Kaufman, JD; Stahl, SJ; Wingfield, PT; Bax, A (2001). "Micelle-Induced Curvature in a Water-Insoluble HIV-1 Env Peptide Revealed by NMR Dipolar Coupling Measurement in Stretched Polyacrylamide Gel". J. Am. Chem. Soc. 124 (11): 990–7. doi:10.1021/ja017875d. PMID 11890789.
  5. ^ Fu, Q; Piai, A; Chen, W; Xia, K; Chou, JJ (2019). "Structure determination protocol for transmembrane domain oligomers". Nat Protoc. 176 (6): 1477–89. doi:10.1038/s41596-019-0188-9. PMC 7238434. PMID 31270510.
  6. ^ Pan, L; Fu, T; Zhao, W; Zhao, L; Chen, W; Qiu, C; Liu, W; Liu, Z; Piai, A; Fu, Q; Chen, S; Wu, H; Chou, JJ (2019). "Higher-Order Clustering of the Transmembrane Anchor of DR5 Drives Signaling". Cell. 176 (6): 1477–89. doi:10.1016/j.molcel.2016.01.009. PMC 6529188. PMID 30827683.
  7. ^ Fu, Q; Fu, T; Cruz, AC; Sengupta, P; Wang, S; Siegel, RM; Wu, H; Chou, JJ (2016). "Structural Basis and Functional Role of Intramembrane Trimerization of the Fas/CD95 Death Receptor". Molecular Cell. 61 (4): 602–13. doi:10.1016/j.cell.2019.02.001. PMC 4761300. PMID 26853147.
  8. ^ Call, ME; Wucherpfennig, KW; Chou, JJ (2010). "The structural basis for intramembrane assembly of an activating immunoreceptor complex". Nature Immunology. 11 (11): 1023–29. doi:10.1038/ni.1943. PMC 3215083. PMID 20890284.
  9. ^ Xu, C; Gagnon, E; Call, ME; Schnell, JR; Schwieters, CD; Carman, CV; Chou, JJ; Wucherpfennig, KW (2008). "Regulation of T cell receptor activation by dynamic membrane binding of the CD3epsilon cytoplasmic tyrosine-based motif". Cell. 135 (4): 702–13. doi:10.1016/j.cell.2008.09.044. PMC 2597348. PMID 19013279.
  10. ^ Call, ME; Chou, JJ (2010). "A View into the Blind Spot: Solution NMR Provides New Insights into Signal Transduction Across the Lipid Bilayer". Structure. 18 (12): 1559–69. doi:10.1016/j.str.2010.11.002. PMC 3108049. PMID 21134635.
  11. ^ Dev, J; Park, D; Fu, Q; Chen, J; Ha, HJ; Ghantous, F; Herrmann, T; Chang, W; Liu, Z; Frey, G; Seaman, MS; Chen, B; Chou, JJ (2016). "Structural basis for membrane anchoring of HIV-1 envelope spike". Science. 353 (6295): 172–175. Bibcode:2016Sci...353..172D. doi:10.1126/science.aaf7066. PMC 5085267. PMID 27338706.
  12. ^ Fu, Q; Shaik, MM; Cai, Y; Ghantous, F; Piai, A; Peng, H; Rits-Volloch, S; Liu, Z; Harrison, SC; Seaman, MS; Chen, B; Chou, JJ (2018). "Structure of the membrane proximal external region of HIV-1 envelope glycoprotein". PNAS. 115 (38): E8892 – E8899. Bibcode:2018PNAS..115E8892F. doi:10.1073/pnas.1807259115. PMC 6156635. PMID 30185554.
  13. ^ Piai, A; Dev, J; Fu, Q; Chou, JJ (2017). "Stability and Water Accessibility of the Trimeric Membrane Anchors of the HIV-1 Envelope Spikes". J Am Chem Soc. 139 (51): 18432–18435. doi:10.1021/jacs.7b09352. PMC 5831154. PMID 29193965.
  14. ^ Schnell, JR; Chou, JJ (2008). "Structure and mechanism of the M2 proton channel of influenza A virus". Nature. 451 (7178): 591–5. Bibcode:2008Natur.451..591S. doi:10.1038/nature06531. PMC 3108054. PMID 18235503.
  15. ^ Pielak, RM; Oxenoid, K; Chou, JJ (2011). "Structural investigation of rimantadine inhibition of the AM2-BM2 chimera channel of influenza viruses". Structure. 19 (11): 1655–63. doi:10.1016/j.str.2011.09.003. PMC 5142205. PMID 22078564.
  16. ^ Pielak, RM; Chou, JJ (2010). "Kinetic Analysis of the M2 Proton Conduction of the Influenza Virus". J Am Chem Soc. 132 (50): 17695–7. doi:10.1021/ja108458u. PMC 3183502. PMID 21090748.
  17. ^ Ouyang, B; Xie, S; Berardi, MJ; Zhao, X; Dev, J; Yu, W; Sun, B; Chou, JJ (2013). "Unusual architecture of the p7 channel from hepatitis C virus". Nature. 498 (7455): 521–5. Bibcode:2013Natur.498..521O. doi:10.1038/nature12283. PMC 3725310. PMID 23739335.
  18. ^ Chen, W; Dev, J; Mezhyrova, J; Pan, L; Piai, A; Chou, JJ (2018). "Unusual architecture of the p7 channel from hepatitis C virus". Structure. 26 (4): 627–634. doi:10.1038/nature12283. PMC 3725310. PMID 23739335.
  19. ^ Bruschweiler, S; Yang, Q; Run, C; Chou, JJ (2015). "Substrate Modulated Dynamics of the ADP/ATP Transporter Revealed by NMR Relaxation Dispersion". Nat Struct Mol Biol. 22 (8): 636–41. doi:10.1038/nsmb.3059. PMC 4527935. PMID 26167881.
  20. ^ Williamson, JA; Cho, SH; Ye, J; Collet, JF; Beckwith, JR; Chou, JJ (2015). "Structure and multistate function of the transmembrane electron transporter CcdA". Nat Struct Mol Biol. 22 (10): 809–14. doi:10.1038/nsmb.3099. PMC 7871232. PMID 26389738.
  21. ^ Cao, C; Wang, S; Cui, T; Su, XC; Chou, JJ (2017). "Ion and inhibitor binding of the double-ring ion selectivity filter of the Mitochondrial Calcium Uniporter". PNAS. 114 (14): E2846 – E2851. Bibcode:2017PNAS..114E2846C. doi:10.1073/pnas.1620316114. PMC 5389301. PMID 28325874.
  22. ^ "The Harvard Biophysics Graduate Program". biophysics.fas.harvard.edu.
  23. ^ "Home". www.lsrf.org.
  24. ^ "The Smith Family New Investigator Award (2005)".
  25. ^ "The Alexander and Margaret Stewart Trust Award (2005)".
  26. ^ "Pew Biomedical Scholars". pew.org.
  27. ^ "Giovanni Armenise-Harvard Junior Faculty Award (2006)".
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