Shi-Hua Xiang

Dr. Shi-Hua Xiang
Associate Professor
402-472-4559
SXIANG2@UNL.EDU

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Faculty Profile

About

As a formally trained virologist, I have been working on viruses for more than 20 years, including HIV/SIV, Ebola/Marburg, Zika/Dengue, Ovine lentivirus (OPPV), and swine influenza. My research is mainly concerned with viral entry, so the interactions between viral envelope glycoproteins and host cellular receptors are a major focus of my laboratory. I have expertise in structural biology, which is valuable for deciphering the molecular mechanisms of viral entry and also for designing of antiviral drugs and vaccine designs. For antiviral research, I also have working experience in research and development at Pfizer as a Senior Scientist. Therefore, my lab can provide training for students in the fundamental basics in virology as well as the applications for antiviral research and development.

Education

  • Postdoc in HIV Entry, Harvard Medical School, Boston, 2004
  • Postdoc in HIV Evolution, University of Washington, Seattle, 1998
  • Postdoc in Pharmacogenetics, Westmead Hospital & Australian Heart Institute, 1998
  • Ph.D. in Microbiology, University of Sydney, Sydney, Australia, 1995
  • B.S. in Biology, Hunan Normal University, Changsha, 1982

Grants

  • NIH 5R21AI151483-02
    Xiang (PI)
    01/01/2021-12/31/2022
    Structure-based Design of Peptide Entry Inhibitors against Ebola Virus Infection
  • NIH 1R21AI126299-01A1
    Xiang (PI)
    07/01/2017-06/30/2022
    Mucosal Delivery and Retention of Ebola Inhibitor Scytovirin Using Lactobacillus

Awards and Honors

  • Bill and Melinda Gates Award (Phase II in Grand Challenges Explorations), 2011
  • Bill and Melinda Gates Award (Phase I in Grand Challenges Explorations), 2008
  • CJ Martin Fellowship Award, Australian National Health and Medical Research Council, 1997-2001
  • Graduate Scholarship, University of Sydney, 1990-1994

Patents

  • Methods of treating or preventing Zika virus infection. Patent No. US11135219B2, Oct 5, 2021. Inventors: Shi-Hua Xiang, Nicholas Palermo, Asit K. Pattnaik, Aryamav Pattnaik. Assignee: NUtech Ventures Lincoln, NE.
  • Conformationally Stabilized HIV Envelope Immunogens. US 08715686 B2. May. 6, 2014. Inventors: Peter Kwong, John Mascola, Gary Nabel, Richard Wyatt, Barna Dey, Ling Xu, Tongqing Zhou, Joseph Sodroski, Wen Yuan, Shi-Hua Xiang. Current Assignee: US Department of Health and Human Services Dana Farber Cancer Institute Inc.
  • WW-domain-activated extracellular vesicles targeting HIV. International patent: WO2022/081957 A1, April 12, 2022. Inventors: Quan Lu (Harvard University, MA), Shi-Hua Xiang (University of Nebraska-Lincoln, NE).

Other

Contributions to Science

  1. Antiviral drug research. I led antiviral research against Zika and Ebola by using structure-based technology such as in-silico screening, molecular modeling and docking, and structural design to develop drugs/inhibitors against viral infections. One compound (TPB) targeting Zika polymerase (RdRp) was found to be potent against Zika infection with the IC50 in the nanomolar range and the Selective index (SI) value of 206, which has been patented (a and c). We have also identified some inhibitors against filovirus infection (Ebola and Marburg) targeting the receptor (NPC1) binding site. The data was published (b).
  1. 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 Research. 2018. Mar;151:78-86. PMID: 29274845.
  2. Wang LL, Palermo N, Estrada L, Thompson C, Patten JJ, Anantpadma M, Davey RA, Xiang SH. Identification of filovirus entry inhibitors targeting the endosomal receptor NPC1 binding site. Antiviral Res. 2021 Mar 8; PMCID: PMC8088776. (Highlight Article for May 2021).
  3. Patent: Methods of treating or preventing Zika virus infection. Patent No. US11135219B2, Oct 5, 2021. Inventors: Shi-Hua Xiang, Nicholas Palermo, Asit K. Pattnaik, Aryamav Pattnaik. Assignee: NUtech Ventures Lincoln, NE.
  1. HIV envelope structure and function. My research on HIV/AIDS has been focused on the HIV/SIV envelope gp120 structure and function. Because gp120 is the HIV virion surface protein, it is important for viral entry, but it is also significant in the study of intervention strategies, including drug and vaccine design. I have been working for more than two years in this field, and my major contribution is to stabilize the HIV envelope glycoprotein structure for vaccine and drug design. For example, I found the 375S/W mutant conformation and the V3-loop role in stabilizing the envelop trimer. I am the co-inventor for two important patents on using the stabilized HIV envelope as a vaccine immunogen (listed one in b), and another MPER based HIV vaccine patent (c).
  1. Xiang SH, Kwong PD, Gupta R, Rizzuto CD, Casper DJ, Wyatt R, Wang L, Hendrickson WA, Doyle ML, Sodroski J. Mutagenic stabilization and/or disruption of a CD4-bound state reveals distinct conformations of the human immunodeficiency virus type 1 gp120 envelope glycoprotein. J Virology 2002 Oct;76(19):9888-99. PMCID: PMC136507
  2. Patent: Conformationally Stabilized HIV Envelope Immunogens. US 08715686 B2. May. 6, 2014. Inventors: Peter Kwong, John Mascola, Gary Nabel, Richard Wyatt, Barna Dey, Ling Xu, Tongqing Zhou, Joseph Sodroski, Wen Yuan, Shi-Hua Xiang. Current Assignee: US Department of Health and Human Services Dana Farber Cancer Institute Inc.
  3. Patent: WW-Domain Activated Extracellular Vesicles Targeting HIV. WO2022/081957A1. Inventors: Quan Lu (Harvard University), Shi-Hua Xiang (University of Nebraska-Lincoln).
  1. Commensal bacterial applications for antiviral research. My lab has been developing a commensal bacteria-based platform for combating virus infections, such as using lactic acid bacteria (LAB) for delivering inhibitors or vaccines. We have successfully engineered a Lactobacillus acidophilus strain for the surface display of human CD4 to block HIV infection, which has been demonstrated in humanized mice (b). We have also engineered an E. coli strain for surface display of VRC01 single-chain antibody to neutralize HIV (a). Recently, we have been using this platform for developing mucosal-based vaccines against the new coronavirus (SARS-2).
  1. Wang LX, Mellon M, Bowder D, Quinn M, Shea D, Wood C, Xiang SH. Escherichia coli surface display of single-chain antibody VRC01 against HIV-1 infection. Virology 2015 Jan 15; 475:179-86. PMCID: PMC4337897.
  2. Wei W, Wiggins J, Hu D, Vrbanac V, Bowder D, Mellon M, Tager A, Sodroski J, and Xiang SH. 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). PMCID: PMC6450108.

Location

MOLR 337
Nebraska Center for Virology
4240 Fair Street
Lincoln, NE 68583-0900

Appointment

90% Research, 10% Teaching

Research Areas

  • Virology

Professional Society Memberships

  • American Association for the Advancement of Science (AAAS)
  • American Society for Virology (ASV)
  • International Society for Vaccines (ISV)
  • International Antiviral Society (ISA)
Lab Website