Research Statement
Our laboratory broadly focuses on the molecular mechanism and regulation of antigen processing and presentation that involved in autoimmunity and infectious diseases. A major interest is the molecular mechanism of processing disulfide bond bearing antigens. GILT (gamma-interferon inducible lysosomal thiol-reductase) is a unique enzyme functioning in unfolding disulfide bond at acidic pH in MHC class II antigen processing and presentation pathway. We utilize various techniques, including site-specific mutagenesis, CRISPR knock-out library screening, single-particle cryo-EM, mouse models, to characterize the molecular and structural mechanism of GILT, and identify novel regulators that modulate its activity. GILT biological function in different diseases, such as malaria infection, diet induced obesity, multiple sclerosis, is also characterized with mouse models.
We also interest in mechanisms involved in quality control of epitope presentation in adaptive immunity and immunological tolerance. HLA-DM plays critical role in MHC class II pathway by catalyzing peptide loading and exchange (DM editing), determining the repertoire of peptides presented to CD4+ T cells. We are particularly interested in studying the biochemical mechanism of DM editing and the role of DM for its sensitivity on editing of peptides bound to MHC class II molecules that associated with autoimmune diseases, such as type 1 diabetes.
Education History
| Internship |
ARUP Laboratories Clinical Immunology |
Intern |
|---|---|---|
| Doctoral Training |
University of Utah Microbiology and Immunology |
Ph.D. |
| Postdoctoral Fellowship |
University of Utah |
Postdoctoral Fellow |
| Doctoral Training |
Huazhong Agricultural University Biochemistry and Molecular Biology |
Ph.D. |
| Undergraduate |
Huazhong Agricultural University Agronomy |
B.S. |
Selected Publications
- Joshi HR, Hill HR, Zhou Z, He X, Voelkerding KV, Kumnovics A (2020). Frontline Science: Cxxc5 expression alters cell cycle and myeloid differentiation of mousehematopoietic stem and progenitor cells. J Leukoc Biol, 108, 459-484.
- Reyes-Vargas E, Barker AP, Zhou Z, He X, Jensen PE (2020). HLA-DM catalytically enhances peptide dissociation by sensing peptide-MHC class II interactions throughout the peptide binding cleft. J Biol Chem, 195(10), 2959-2973.
- Zhao P, Wang P, Dong S, Zhou Z, Cao Y, Yagita H, He X, Zheng S, Fisher S, Fujinami R, Chen M (2019). Depletion of PD-1-positive cells ameliorates autoimmune disease. Nat Biomed Eng, 3, 292-305.
- Zhou Z, Reyes-Vargas E, Escobar H, Chang KY, Barker AP, Rockwood AL, Delgado JC, He X, Jensen PE (2017). Peptidomic analysis of type 1 diabetes associated HLA-DQ molecules and the impact of HLA-DM on peptide repertoire editing. Eur J Immunol, 47(2), 314-326.
- Zhou Z, Reyes-Vargas E, Escobar H, Rudd B, Rockwood AL, Delgado JC, He X, Jensen PE (2016). Type 1 diabetes associated HLA-DQ2 and DQ8 molecules are relatively resistant to HLA-DM mediated release of invariant chain-derived CLIP peptides. Eur J Immunol, 46(4), 834-45.
- Zhou Z, He X, Jensen PE (2014). Molecular identification of an MHC class Ib (H2-Q9) restricted T cell receptor specific for a mouse polyomavirus peptide VP2.139. 1(3), 8-15.
- Zhou Z, Jensen PE (2013). Structural Characteristics of HLA-DQ that May Impact DM Editing and Susceptibility to Type-1 Diabetes. [Review]. Front Immunol, 4, 262.
- Zhou Z, Callaway KA, Weber DA, Jensen PE (2009). Cutting edge: HLA-DM functions through a mechanism that does not require specific conserved hydrogen bonds in class II MHC-peptide complexes. J Immunol, 183(7), 4187-91.
- Hu L, Wu H, Zhou Z, Lin Y (2007). Introduction of citrate synthase gene into an elite indica rice restorer line Minghui 86 by Agrobacterium mediated method. 4(2), 160-166.
Global Impact
Education History
| Type | School | Degree |
|---|---|---|
| Doctoral Training | Huazhong Agricultural University Biochemistry and Molecular Biology |
Ph.D. |
| Undergraduate | Huazhong Agricultural University Agronomy |
B.S. |