Lin Jiang, Ph.D.

David Geffen School of Medicine at UCLA

Member of Biochemistry, Biophysics and Structural Biology GPB Home Area at UCLA

Principal Investigator, Jiang Laboratory

Jiang Lab
Neuroscience Research Building, Room 475B
635 Charles E. Young Drive South
Los Angeles, CA 90095
Tel: (310) 206-0908
Email: LinJiang@mednet.ucla.edu

Biography

Jiang started his journey in science when he went to Peking University, where he earned a B.S. degree in Chemistry and an M.S. degree in Physical Chemistry with Distinction. He did research in protein interactions with Luhua Lai at Peking University and found his passion for structure-based protein modeling and drug design research. He then went to the University of Washington for Ph.D. in Biochemical Science. There he worked on enzyme design in the laboratory of David Baker, using computational and experimental methods to engineer protein catalysts for those chemical transformations that naturally occurring enzymes cannot catalyze. After completing his Ph.D. work, he pursued postdoctoral training with David Eisenberg at UCLA, applying his computational methods to develop new therapeutics for protein aggregation diseases. He joined the UCLA faculty in 2015 and is currently an Assistant Professor in Residence of Neurology.

Specialty

Computational Structural Biology; Drug Design; Peptidomimetic Design; Structure-based Modeling and Design; Protein/Peptide Self-assemblies in Neurodegenerative Disorders.

Affiliations

COMPLETED - Project 3: Design and Structure of Drugs against AD

Research Interests

Computational structural biology and drug design for Alzheimer's, Parkinson's, Lou Gehrig's disease and other degenerative disorders. Current research is driven by two key questions: How do unfolded or misfolded proteins self-associate into abnormal aggregates? How do these aggregates propagate and lead to disease? The findings of the research will identify new drug targets, develop new therapeutics and design new therapeutic compounds or peptides for the treatment of neurodegenerative disorders.

Education and Degrees

1994-1999 -- B.S. in Chemistry (Computer Science Minor), Peking University, Beijing, China.

1999-2002 -- M.S. in Physical Chemistry, Peking University, Beijing, China.

2002-2008 -- Ph.D. in Biochemistry, University of Washington, Seattle, WA
Thesis: Novel Catalysts by Computational Enzyme Design. (Advisor: David Baker)

2008-2009 -- Postdoctoral Fellow, University of Washington.

2009-2015 --  Research Associate, University of California, Los Angeles. (Advisor: David S. Eisenberg)

Awards and Honors

2000 -- Research Innovation Award, Peking University.

2002 -- Outstanding Thesis Award, Peking University.

2008 -- Cutting Edge Chemistry in 2008, Chemistry World.

2008 -- Top Breakthroughs in Computational Science, Scientific Discovery through. Advanced Computing (SciDAC), Department of Energy (DOE).

2014 -- MBI Postdoctoral Recognition Award of Excellence, UCLA.

Publications

J.A. Rodriguez*, M. Ivanova*, M.R. Sawaya*, D. Cascio*, F. Reyes*, Shi D, S. Sangwan, E. Guenther, Johnson L, M. Zhang, L. Jiang, M.A. Arbing, J. Hattne, J. Whitelegge, A. Brewster, M. Messerschmidt, S. Boutet, N.K. Sauter, B. Nannenga, T. Gonen, D. Eisenberg "Structure of the toxic core of α-synuclein from invisible crystals" Nature accepted.

Y.T. Lai, L. Jiang, W. Chen, T.O. Yeates "On the predictability of the orientation of protein domains joined by a spanning alpha-helical linker." Protein Eng Des Sel. 2015 Aug 4. pii: gzv035. [Epub ahead of print] PMID: 26243886

E.Y. Hayden, G. Yamin, S. Beroukhim, B. Chen, M. Kibalchenko, L. Jiang, L. Ho, J. Wang, G.M. Pasinetti, D.B. Teplow “Inhibiting amyloid β-protein assembly: Size-activity relationships among grape seed-derived polyphenols” Journal of Neurochemistry 2015 Jul 30. doi: 10.1111/jnc.13270. [Epub ahead of print] PMID: 26228682

A.W. James, J. Shen, X. Zhang, G. Asatrian, R. Goyal, J. H. Kwak, L. Jiang, B. Bengs, C.T. Culiat, A.S. Turner, H.B. Seim III, B.M. Wu, K. Lyons, J.S. Adams, K. Ting, C. Soo “NELL-1 in the treatment of osteoporotic bone loss” Nature Communication 2015 Jun 17;6:7362. doi: 10.1038/ncomms8362. PMID: 26082355

T.D. Kurt, L. Jiang, N. Fernández-Borges, C. Bett, J. Liu, T. Yang, T. Spraker, J. Castilla, D. Eisenberg, Q. Kong, and C.J. Sigurdson “Human prion protein sequence elements impede cross-species chronic wasting disease transmission.” Journal of Clinical Investigation. 2015 Apr 1;125(4):1485-96. doi: 10.1172/JCI79408. PMID: 25705888. Science featured this work in its Editor’s Choice (Science, 348(6230): 88, Apr. 2015).

L. Gu, C. Liu, J.C. Stroud, S. Ngo, L. Jiang, Z. Guo “Antiparallel triple-strand architecture for prefibrillar Aβ42 oligomers” Journal of Biological Chemistry 2014 Sep 26; 289 (39), 27300-27313. PMID: 25118290

T.D. Kurt, L. Jiang, C. Bett, D. Eisenberg, C.J. Sigurdson “A proposed mechanism for the promotion of prion conversion involving a strictly conserved tyrosine residue in the β2-α2 loop of PrPC” Journal of Biological Chemistry 2014 Mar 4. doi: 10.1074/jbc.M114.549030. PMID: 24596090

L. Jiang*, C. Liu*, D. Leibly, M. Landau, M. Zhao, M.P. Hughes, D. Eisenberg “Structure-based discovery of fiber-binding compounds that reduce the cytotoxicity of amyloid beta” eLife 2013. July 16; 2:e00857. PMID: 23878726. eLife Insight and other scientific journal featured this work (eLife; 2:e01089, Jul. 2013; Am J Alzheimers Dis Other Demen 2013 Sep; 28(6):642-3).

C. Liu*, M. Zhao*, L. Jiang*, J. Park, P. Cheng, M.R. Sawaya, D. Guo, A. Berk, J.S. Nowick, D. Eisenberg “Out-of-register β-sheets suggest a pathway to toxic amyloid aggregates” Proceedings of the National Academy of Sciences USA, 2012 Dec 18; 109(51):20913-8.

E.A. Althoff*, L. Wang*, L. Jiang*, L. Giger, J.K. Lassila, Z. Wang, M. Smith, S. Hari, P. Kast, D. Herschlag, D. Hilvert, D. Baker “Robust design and optimization of retro-aldol enzymes” Protein Science. 2012 May; 21(5): 717-26. PMID: 22407837

L. Wang , E.A. Althoff, J. Bolduc, L. Jiang, J. Moody, J.K. Lassila, L. Giger, D. Hilvert, B. Stoddard, D. Baker. “Structural analyses of covalent enzyme-substrate analog complexes reveal strengths and limitations of de novo enzyme design” Journal of Molecular Biology, 2012 Jan 20; 415(3):615-25. PMID: 22075445

S.A. Sievers*, J Karanicolas*, H.W. Chang*, A. Zhao*, L. Jiang*, O. Zirafi, J.T. Stevens, J. Munch, D. Baker, D. Eisenberg “Structure-based design of non-natural amino acid inhibitors of amyloid fibrillation” Nature. 2011 Jun 15; 475(7354): 96-100. PMID: 21677644 (*Co-first author) (Faculty of 1000 Nomination: rated as Must Read). Nature Methods featured this work (Nature Methods, 8(8): 615, Jul. 2011).

M. Landau, M.R. Sawaya, K.F. Faull, A. Laganowsky, L. Jiang, S.A. Sievers, J. Liu, J.R. Barrio, D. Eisenberg “Towards a pharmacophore for amyloid” Plos Biology, 2011. Jun 14; 9(6): e1001080. PMID: 21695112

L. Jiang*, E.A. Althoff*, F.R. Clemente, L. Doyle, D. Röthlisberger, A. Zanghellini, J.L. Gallaher, J.L. Betker, F. Tanaka, C.F. Barbas, D. Hilvert, K.N. Houk, B. Stoddard, D. Baker. “De novo computational design of retro-aldol enzymes” Science. 2008 Mar 7; 319(5868): 1387-1391. . PMID: 18323453. (Faculty of 1000 Nomination: rated as Exceptional). This papers was featured by Nature in “Research Highlight 2008” (Nature 456: 841, Dec. 2008). Multiple scientific journals commented on these research works (Nature Chemical Biology 4(5): 273-275, May 2008; Angew. Chem. Int. Ed., 47(41): 7802-7803, Sep. 2008; Chemistry & Biology, 15(5): 421-423, May 2008; Chemical & Engineering News, 86(10): 13, Mar. 2008; Technology Review, 111(3): 94, May 2008; Chemistry World, 5(4), Apr. 2008).

D. Röthlisberger*, O. Khersonsky*, A.M. Wollacott*, L. Jiang, J. DeChancie, J. Betker, J.L. Gallaher, E.A. Althoff, A. Zanghellini, O. Dym, S. Albeck, K.N. Houk, D.S. Tawfik, D. Baker “Novel Kemp elimination catalysts by computational enzyme design” Nature. 2008 May 8; 453 (7192): 190-195. PMID: 18354394. (Faculty of 1000 Nomination: rated as Exceptional). This paper was featured by Nature in “THE YEAR IN NATUE” (Nature 456: xii, Dec. 2008).

A. Zanghellini*, L. Jiang*, A. Wollacott, G. Cheng, J. Meiler, E.A. Althoff, D. Röthlisberger, D. Baker. “New algorithms and an in silico benchmark for computational enzyme design” Protein Science, 2006. Dec; 15(12): 2785-2794. PMID: 17132862

L. Jiang, B. Kuhlman, T. Kortemme, D. Baker. “A solvated rotamer approach to modeling water-mediated hydrogen bonds at protein-protein interfaces” Proteins, 2005. Mar 1; 58(4): 893-904. PMID: 15651050 (Featured as cover story) (Faculty of 1000 Nomination: rated as Recommended)

Z. Liu, L. Jiang, S. Liang, Y. Gao, W. Li, Y. Han, L. Lai. “Beyond rotamer library: genetic algorithm combined with disturbing mutation process for upbuilding protein side-chain” Proteins, 2003. Jan 1; 50(1): 49-62. PMID: 12471599

L. Jiang and L. Lai. “CH...O hydrogen bonds at protein-protein interfaces” Journal of Biological Chemistry, 2002. Oct 4; 277(40): 37732-40. PMID: 12119293

L. Jiang, Y. Gao, F. Mao, Z. Liu and L. Lai. “Potential of mean force for protein-protein interaction studies” Proteins, 2002. Feb 1; 46: 190-196. PMID: 11807947