Summary

Jianliang Xu, Ph.D., received his doctoral degree from Nanjing University, School of Life Sciences, in China where he studied the transcription regulation of oncogene protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3). Subsequently, Dr. Xu studied the molecular mechanism of immunoglobulin gene diversification under the mentorship of Professor Tasuku Honjo at Kyoto University. He joined the Laboratory of Lymphocyte Nuclear Biology at the NIAMS in 2014, where he is now a Research Fellow.

Dr. Xu’s research on B lymphocytes has expanded from deciphering the mechanism of antibody diversification and maturation in cell culture models to establishing experimental mouse models and creating novel tools for antibody drug development. He has developed knock-in mouse strains to study transcription factors dynamic in primary B cells. Recently, he has engineered a camelized mouse model (nanomice, NIH Employee Invention Report E-209-2020-0) in which B cells no longer express conventional heavy/light chain-paired IgM and IgG1. Instead, both IgM and IgG1 are heavy chain-only, and their variable domains are from camelid animals. Using llamas and the novel nanomouse model, Dr. Xu identified two groups of nanobodies that can potently neutralize SARS-CoV-2 and its circulating variants.

Research Statement

Dr. Xu's long-term goal is to establish efficient nanobody development platforms and use them to develop nanobodies that broadly neutralize viruses that cause infectious diseases such as COVID-19, AIDS, influenza, etc. These platforms will be based on heavy chain-only antibody-producing animals, such as llamas and engineered nanomice, as well as potential new versions of mouse models. Gaining knowledge of how to elicit strong and preferable immune responses in these animal models (upstream vaccine design) and how to extract and optimize functional nanobodies (downstream antibody drug production) will be the critical component of the platforms.

Scientific Publications

Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants.

Xu J, Xu K, Jung S, Conte A, Lieberman J, Muecksch F, Lorenzi JCC, Park S, Schmidt F, Wang Z, Huang Y, Luo Y, Nair MS, Wang P, Schulz JE, Tessarollo L, Bylund T, Chuang GY, Olia AS, Stephens T, Teng IT, Tsybovsky Y, Zhou T, Munster V, Ho DD, Hatziioannou T, Bieniasz PD, Nussenzweig MC, Kwong PD, Casellas R
Nature.
2021 Jul;
595(7866).
doi: 10.1038/s41586-021-03676-z
PMID: 34098567

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants.

Wang Z, Schmidt F, Weisblum Y, Muecksch F, Barnes CO, Finkin S, Schaefer-Babajew D, Cipolla M, Gaebler C, Lieberman JA, Oliveira TY, Yang Z, Abernathy ME, Huey-Tubman KE, Hurley A, Turroja M, West KA, Gordon K, Millard KG, Ramos V, Da Silva J, Xu J, Colbert RA, Patel R, Dizon J, Unson-O'Brien C, Shimeliovich I, Gazumyan A, Caskey M, Bjorkman PJ, Casellas R, Hatziioannou T, Bieniasz PD, Nussenzweig MC
Nature.
2021 Apr;
592(7855).
doi: 10.1038/s41586-021-03324-6
PMID: 33567448

SAMHD1-mediated dNTP degradation is required for efficient DNA repair during antibody class switch recombination.

Husain A, Xu J, Fujii H, Nakata M, Kobayashi M, Wang JY, Rehwinkel J, Honjo T, Begum NA
EMBO J.
2020 Aug 3;
39(15).
doi: 10.15252/embj.2019102931
PMID: 32511795

Myc Regulates Chromatin Decompaction and Nuclear Architecture during B Cell Activation.

Kieffer-Kwon KR, Nimura K, Rao SSP, Xu J, Jung S, Pekowska A, Dose M, Stevens E, Mathe E, Dong P, Huang SC, Ricci MA, Baranello L, Zheng Y, Tomassoni Ardori F, Resch W, Stavreva D, Nelson S, McAndrew M, Casellas A, Finn E, Gregory C, St Hilaire BG, Johnson SM, Dubois W, Cosma MP, Batchelor E, Levens D, Phair RD, Misteli T, Tessarollo L, Hager G, Lakadamyali M, Liu Z, Floer M, Shroff H, Aiden EL, Casellas R
Mol Cell.
2017 Aug 17;
67(4).
doi: 10.1016/j.molcel.2017.07.013
PMID: 28803781

APE1 is dispensable for S-region cleavage but required for its repair in class switch recombination.

Xu J, Husain A, Hu W, Honjo T, Kobayashi M
Proc Natl Acad Sci U S A.
2014 Dec 2;
111(48).
doi: 10.1073/pnas.1420221111
PMID: 25404348

C-terminal region of activation-induced cytidine deaminase (AID) is required for efficient class switch recombination and gene conversion.

Sabouri S, Kobayashi M, Begum NA, Xu J, Hirota K, Honjo T
Proc Natl Acad Sci U S A.
2014 Feb 11;
111(6).
doi: 10.1073/pnas.1324057111
PMID: 24469810

VEGF promotes the transcription of the human PRL-3 gene in HUVEC through transcription factor MEF2C.

Xu J, Cao S, Wang L, Xu R, Chen G, Xu Q
PLoS One.
2011;
6(11).
doi: 10.1371/journal.pone.0027165
PMID: 22073279

Education

Nanjing University
Ph.D., Biology (2010)

Nanjing University
M.S., Biochemistry and Molecular Biology (2007)

Nanjing Agriculture University
B.S., Bioengineering (2004)

Experience

Research Fellow
NIAMS/NIH (2018-Present)

Postdoctoral Fellow
NIAMS/NIH (2014-2018)

Postdoctoral Fellow
Kyoto University (2010-2014)

Last Updated: September 2021