Shi-Hua Xiang, Ph.D.

Associate Professor
Nebraska Center for Virology
School of Veterinary Medicine and Biomedical Sciences
University of Nebraska – Lincoln
4240 Fair Street, Morrison Center
Lincoln, NE 68583-0900
Phone: (402) 472-4520
Fax: (402) 472-3323
Email: sxiang2@unl.edu

Research Interests

My current research interests have been focused on antivirals. We utilize the cutting-edge technologies to develop effective countermeasures for fighting against human or animal viral infectious diseases. The primary viral pathogens we have been working on in the lab include Human immunodeficiency virus (HIV) and Simian immunodeficiency virus (SIV), Ebolaviruses (EBOV), Zika virus (ZIKV), Dengue virus (DENV), Ovine progressive pneumonia virus (OPPV), and Bovine viral diarrhea virus (BVDV). Two major approaches have been developing in the lab which can be summarized below:

     I.                    Structure Based Drug/Vaccine Design against Viral Infectious Diseases

We evaluate the target proteins in the virus life cycle for which the structural information is available. We use the structure based approaches such as molecular modeling, docking, in silico screening, and structure based design to design inhibitors for drug development or design immunogens for vaccine development. Because this design is a specific target based it will increase the clinical effect and reduce the side-effect. In particular, we will use the antibody binding information to design peptides and small molecules for targeting (see the design strategy Figure below).

     II.                    Commensal Bacteria Based Delivery System for Virus Infection Control

Commensal bacteria naturally reside in human or animal body in large numbers and supply certain metals, hormones and other important nutrients. So it is rationale that we can employ these bacteria and manipulate them for therapeutic applications against human or animal diseases. We have been developing lactobacillus based delivery system to deliver therapeutics or vaccines into the mucosal surfaces for anti-viral diseases such as HIV and Ebola. Since the commensal bacteria can colonize in the body it is likely to achieve a long-term efficacy. This delivery system can be described as the Figure below.



Research Articles

Lu W, Chen S, Yu J, Behrens R, Wiggins J, Sherer N, Liu SL, Xiong Y, Xiang SH, Wu L. The Polar Region of HIV-1 Envelope Protein Determines Viral Fusion and Infectivity by Stabilizing gp120-gp41 Association. J Virol. 2019 Jan 16. pii: JVI.02128-18. doi: 10.1128/JVI.02128-18. PMID: 30651369.

Wang F, Zhou S, Qi D, Xiang SH, Wong ET, Wang X, Fonkem E, Hsieh TC, Yang J, Kirmani B, Shabb JB, Wu JM, Wu M, Huang JH, Yu WH, Wu E. Nucleolin Is a Functional Binding Protein for Salinomycin in Neuroblastoma Stem Cells. J Am Chem Soc. 2019 Feb 27;141(8):3613-3622. PMID: 30689374.

Wei W, Wiggins J, Hu D, Vrbanac V, Bowder D, Mellon M, Tager A, Sodroski J, and Xiang SH.-H. Blocking HIV-1 infection by chromosomal integrative expression of human CD4 on the surface of Lactobacillus accidophilus ATCC 4356. J Virol 2019 Apr 3;93(8). PMID: 30728264.

Pattnaik A, Palermo N, Sahoo BR, Yuan Z, Hu D, Annamalai AS, Vu HLX, Correas I, Prathipati PK, Destache CJ, Li Q, Osorio FA, Pattnaik AK, Xiang SH.  Discovery of a non-nucleoside RNA polymerase inhibitor for blocking Zika virus replication through in silico screening. Antiviral Res. 2018. Mar;151:78-86. PMID: 29274845.

Bowder D, Thompson D, Durst K, Hollingsead H, Hu D, Wei W, and Xiang SH. Characterization of Twin-Cysteine Motif in the V2-loop Region of gp120 in Primate Lentiviruses. Virology, 2018 Jun; 519:180-18. PMID: 29729526.

Bowder D, Hollingsead H, Durst K, Hu D, Wei W, Wiggins J, Medjahed H, Finzi A, Sodroski J, Xiang SH. Contribution of the gp120 V3 loop to envelope glycoprotein trimer stability in primate immunodeficiency viruses. Virology, 2018 Jun 21; 521:158-168. PMID: 29936340.

Persistence of SIV in the brain of SIV-infected Chinese rhesus macaques with or without antiretroviral therapy. Perez S, Johnson AM, Xiang SH, Li J, Foley BT, Doyle-Meyers L, Panganiban A, Kaur A, Veazey RS, Wu Y, Ling B., J Neurovirol. 2017 Nov 27. doi: 10.1007/s13365-017-0594-0.

Zika Virus Encoding Non-Glycosylated Envelope Protein is Attenuated and Defective in Neuroinvasion. Annamalai AS, Pattnaik A, Sahoo BR, Muthukrishnan E, Natarajan SK, Steffen D, Vu HLX, Delhon G, Osorio FA, Petro TM, Xiang SH, Pattnaik AK. J Virol. 2017 Sep 20. pii: JVI.01348-17. doi: 10.1128/JVI.01348-17.

Tryptophan 375 stabilizes the outer-domain core of gp120 for HIV vaccine immunogen design. Hu D, Bowder D, Wei W, Thompson J, Wilson MA, Xiang SH. Vaccine. 2017 May 25;35(23):3067-3075. doi: 10.1016/j.vaccine.2017.04.054. Epub 2017 Apr 29.

Mechanistic understanding of N-glycosylation in Ebola virus glycoprotein maturation and function. Wang B, Wang Y, Frabutt DA, Zhang X, Yao X, Hu D, Zhang Z, Liu C, Zheng S, Xiang SH, Zheng YH. J Biol Chem. 2017 Apr 7;292(14):5860-5870. doi: 10.1074/jbc.M116.768168. Epub 2017 Feb 14.

Lineage-Specific Differences between the gp120 Inner Domain Layer 3 of Human Immunodeficiency Virus and That of Simian Immunodeficiency Virus. Ding S, Medjahed H, Prévost J, Coutu M, Xiang SH, Finzi A. J Virol. 2016 Oct 28;90(22):10065-10073. Print 2016 Nov 15.

Sulfotyrosine dipeptide: Synthesis and evaluation as HIV-entry inhibitor. Ju T, Hu D, Xiang SH, Guo J. Bioorg Chem. 2016 Oct;68:105-11. doi: 10.1016/j.bioorg.2016.07.012. Epub 2016 Jul 25.

A Highly Conserved gp120 Inner Domain Residue Modulates Env Conformation and Trimer Stability. Ding S, Tolbert WD, Prévost J, Pacheco B, Coutu M, Debbeche O, Xiang SH, Pazgier M, Finzi A. J Virol. 2016 Sep 12;90(19):8395-409. doi: 10.1128/JVI.01068-16. Print 2016 Oct 1.

Genome-Wide Search for Host Association Factors during Ovine Progressive Pneumonia Virus Infection. Thompson J, Ma F, Quinn M, Xiang SH. PLoS One. 2016 Mar 7;11(3):e0150344. doi: 10.1371/journal.pone.0150344. eCollection 2016.

From crystal structure of α-conotoxin GIC in complex with Ac-AChBP to molecular determinants of its high selectivity for α3β2 nAChR. Lin B, Xu M, Zhu X, Wu Y, Liu X, Zhangsun D, Hu Y, Xiang SH, Kasheverov IE, Tsetlin VI, Wang X, Luo S. Sci Rep. 2016 Mar 1;6:22349. doi: 10.1038/srep22349.

Escherichia coli surface display of single-chain antibody VRC01 against HIV-1 infection. Wang LX, Mellon M, Bowder D, Quinn M, Shea D, Wood C, Xiang SH. Virology. 2015 Jan 15;475:179-86. doi: 10.1016/j.virol.2014.11.018. Epub 2014 Dec 5.

Sumoylation differentially regulates Sp1 to control cell differentiation. Gong L, Ji WK, Hu XH, Hu WF, Tang XC, Huang ZX, Li L, Liu M, Xiang SH, Wu E, Woodward Z, Liu YZ, Nguyen QD, Li DW. Proc Natl Acad Sci U S A. 2014 Apr 15;111(15):5574-9. doi: 10.1073/pnas.1315034111. Epub 2014 Mar 27.

Recent advances on the use of structural biology for the design of novel envelope immunogens of HIV-1. Xiang SH. Curr HIV Res. 2013 Sep;11(6):464-72.

A twin-cysteine motif in the V2 region of gp120 is associated with SIV envelope trimer stabilization. Bohl C, Bowder D, Thompson J, Abrahamyan L, Gonzalez-Ramirez S, Mao Y, Sodroski J, Wood C, Xiang SH. PLoS One. 2013 Jul 23;8(7):e69406. doi: 10.1371/journal.pone.0069406. Print 2013.

Molecular architecture of the uncleaved HIV-1 envelope glycoprotein trimer. Mao Y, Wang L, Gu C, Herschhorn A, Désormeaux A, Finzi A, Xiang SH, Sodroski JG. Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):12438-43. doi: 10.1073/pnas.1307382110. Epub 2013 Jun 11.

Characterization of a dual-tropic human immunodeficiency virus (HIV-1) strain derived from the prototypical X4 isolate HXBc2. Xiang SH, Pacheco B, Bowder D, Yuan W, Sodroski J. Virology. 2013 Mar 30;438(1):5-13. doi: 10.1016/j.virol.2013.01.002. Epub 2013 Jan 29.

The highly conserved layer-3 component of the HIV-1 gp120 inner domain is critical for CD4-required conformational transitions. Désormeaux A, Coutu M, Medjahed H, Pacheco B, Herschhorn A, Gu C, Xiang SH, Mao Y, Sodroski J, Finzi A. J Virol. 2013 Mar;87(5):2549-62. doi: 10.1128/JVI.03104-12. Epub 2012 Dec 19.

Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer. Mao Y, Wang L, Gu C, Herschhorn A, Xiang SH, Haim H, Yang X, Sodroski J. Nat Struct Mol Biol. 2012 Sep;19(9):893-9. doi: 10.1038/nsmb.2351. Epub 2012 Aug 5.

Lineage-specific differences between human and simian immunodeficiency virus regulation of gp120 trimer association and CD4 binding. Finzi A, Pacheco B, Xiang SH, Pancera M, Herschhorn A, Wang L, Zeng X, Desormeaux A, Kwong PD, Sodroski J. J Virol. 2012 Sep;86(17):8974-86. doi: 10.1128/JVI.01076-12. Epub 2012 Jun 13.




Education

Postdoctoral &nbsp Harvard Medical School, Boston, MA


Ph.D.   1995, Microbiology, University of Sydney, Sydney, Australia.


M.S.    1986, Mycology, Huazhong Agaricultural University, Wuhan, China.


B.S. 1982, Biology, Hunan Normal University, Changsha, China




Professional Positions

Associate Professor - University of Nebraska-Lincoln, School of Veterinary Medicine and Biomedical Sciences, 2017-present

Assistant Professor - University of Nebraska-Lincoln, School of Veterinary Medicine and Biomedical Sciences, 2011 - 2017

Instructor, 2004-2010, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.



Honors & Awards

Grand Challenges Explorations (GCE) Awards, Phase I (2008) & Phase II (2011), Bill & Melinda Gates Foundation.

CJ Martin Fellowship Award, 1997, Australian National Health and Medical Research Council (NH&MRC).




Professional Affiliations

NCV Membership 2011 - present

American Society for Virology

American Society for Biochemistry and Molecular Biology

New England Structural Biology Association