The Doctor of Philosophy Seminar and Examination of Dao Xu

Biography

Dao is from Xinjiang, China. He attended the University of Science and Technology of China and recieved a bachelor's degree in biological science in 2016. He attended Oklahoma State University and recieved a master's degree in veterinary biomedical sciences in 2019. He started his PhD program at VMCVM in 2020. His research interests include animal disease models and immunology. In his free time, he likes hiking and watching NBA and movies. 

Funded by

• National Institutes of Health
• Virginia-Maryland College of Veterinary Medicine Office of Research and Graduate Studies

Lay Language Abstract 

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder often occurring in women. SLE is characterized by pathogenic antibody production and inflammation. Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase member. The removal of acetyl groups from lysine residues of histones as well as other nonhistone proteins can be catalyzed by HDAC6. It has been observed that in lupus mouse models, specific HDAC6 inhibition reduces inflammation. Pristane, a naturally occurring hydrocarbon oil, can result in lupus-like illness and persistent inflammation. In this study, sex and age-matched wild type (WT) and HDAC6-/- mice on the C57BL/6 background were injected with 0.5 ml pristane or PBS intraperitoneally at 8-12 weeks of age and were euthanized 10 days or 8 months later. The animals were assessed as they aged. Pristane treatment promoted the population of CD11b+Ly6C++ inflammatory monocytes and CD11b+Ly6G+ neutrophils. Peritoneal recruitment of these inflammatory monocytes and neutrophils in HDAC6-/- mice was significantly decreased compared to the WT mice. Pristane treatment also induced the interferon (IFN) signature genes as determined by qRT-PCR. Furthermore, IFN signature genes were decreased in HDAC6-/- mice compared to the WT mice. In vitro studies in J774 cells revealed that the selective HDAC6 inhibitor (ACY-738) increased acetylation of NF-κB and decreased NF-κB phosphorylation while not inhibiting Stat1-phosphorylation which resulted in inducible nitric oxide synthase (iNOS) production in LPS/IFN-γ stimulated cells. Pristane treatment induced proteinuria in female mice although there were no significant differences between WT and KO animals. HDAC6 deletion significantly inhibited anti-dsDNA IgG level compared with WT mice. Moreover, HDAC6 deletion decreased some lymphocyte populations like Th17 cells after pristane treatment. Taken together these results demonstrate that although HDAC6 inhibition may inhibit some inflammatory pathways, others remain unaffected.

Publications

• Dao Xu, Xin M. Luo, Christopher M. Reilly “HDAC6 Deletion Decreases Pristane-Induced Inflammation” ImmunoHorizons, submitted
• Dao Xu, Evan Bischoff, Xin M. Luo, Christopher M. Reilly “HDAC6 Deletion Decreases Pristane-Induced Lupus” Current Research in Immunology, submitted

Presentations

• Dao Xu. HDAC6 knockout alleviates pristane-induced lupus. BMVS Annual Research Symposium, poster presentation, Blacksburg, VA, March 2024
• Dao Xu. HDAC6 knockout alleviates pristane-induced lupus. BMVS Annual Research Symposium, poster presentation, Blacksburg, VA, March 2023
• Dao Xu. HDAC6 knockout alleviates pristane-induced lupus. American Association of Immunologists annual meeting, poster presentation, Portland, OR, May 2022. 

Examination Graduate Committee

Major Advisor/Chair:

Xin Luo, PhD
Professor of Immunology
Assistant Department Head for Graduate Studies
Department of Biomedical Sciences and Pathobiology

Graduate Advising Committee Members:

Christopher Reilly, PhD

Research Associate Professor at VMCVM
Department of Biomedical Sciences and Pathobiology
Discipline Chair for Cellular Biology and Physiology
Edward Via College of Osteopathic Medicine

C. Allen, PhD, MBA, MS
Professor of Inflammatory Disease
Assistant Department Head for Research Support
Department of Biomedical Sciences and Pathobiology

Rujuan Dai, PhD
Research Assistant Professor
Department of Biomedical Sciences and Pathobiology

Liwu Li, PhD
Professor of Biological Sciences
Department of Biological Sciences