Xiao He

Xiao He, MD, PhD

Languages spoken: English

Academic Information

Departments Primary - Pathology

Divisions:

Academic Office Information

xiao.he@path.utah.edu

Research Interests

  • Immunology
  • Gene Expression

Research Statement

zbtb7b (Zinc finger and BTB domain-containing protein 7B)/Th-POK (T-helper-inducing POZ/Kruppel factor): T lymphocytes, further divided into 2 major subpopulations: CD4 helper and CD8 cytotoxic T cells, play a crucial role in controlling microbial infections and cancer development. zbtb7b is a transcriptional factor, which we cloned from a CD4 helper deficiency (HD) mouse line several years ago. zbtb7b functions as a master regulator in determining the CD4 vs. CD8 T cell lineage choice. A point mutation in zbtb7b gene results in all mature T cells becoming D8 cells in HD mice, while over-expression of this factor leads totally lack of CD8 T cells in zbtb7b transgenic mice. We are looking for the up-stream regulator(s) and down-stream target(s) of zbtb7b. In addition, aberrant expression of zbtb7b causes T cell lymphoma. We are also investigating the potential implication of zbtb7b in CD4 helper cell-deficient and T-ALL patients.

GILT (?-IFN-inducible lysosomal thiol reductase): GILT is a unique thiol reductase, localized in lysosomes, with optimal activity at low pH, and is expressed in Ag presenting cells (APC). GILT is important in processing protein Ag by catalyzing disulfide bond reduction, thus facilitating the unfolding of native Ag containing disulfide bonds for further processing. GILT-/- mice are defective in processing exogenous protein Ag, which contains disulfide bonds, shown that GILT-/- APC is selectively impaired to process/present HEL to some, but not all, epitope specific T cell hybridomas. Moreover, GILT-/- mice are also defective in generation of Ab responses to some Ag. We are actively investigating the cellular and molecular mechanisms underling this deficiency.
CIIEM (MHC Class II Expression Modifier): APCs capture, process and present non-self Ag (from microorganisms or tumor cells) to T lymphocytes to initiate a specific immune response. MHC Class II proteins are expressed on cell surface of the professional APC (B cells, dendritic cells and macrophages). Human T cells also express HLA Class II products and present Ag. In many cases, human T cells can present self-Ag and are implicated in autoimmune diseases. Using bioinformatics, a putative novel gene, CIIEM, was identified and the full length of mouse CIIEM cDNA was cloned. We hypothesize that CIIEM can inhibit the expression of H-2 Class II genes in mouse T cells. Experiments to investigate the biological function of CIIEM are in progress.

Education History

Postdoctoral Fellowship Howard Hughs Medical Institute Research Laboratories
 Postdoctoral Fellow
Medical College of Pennsylvania/Hahnemann University, Department of Microbiology & Immunology
 Postdoctoral Fellow
Doctoral Training Wake Forest University Bowman Gray School of Medicine, Department of Microbiology & Immunology
Medical College of Pennsylvania, Graduate School of Medical Sciences, Dept of Microbiology & Immunol
 PhD
Graduate Training Shanghai Medical University School of Graduate Studies, Department of Pathophysiology
 MS
Chongqing Medical College School of Medicine
 MD

Selected Publications

Journal Article

  1. Kim H, Perovanovic J, Shakya A, Shen Z, German CN, Ibarra A, Jafek JL, Lin NP, Evavold BD, Chou DH, Jensen PE, He X, Tantin D (2020). Targeting transcriptional coregulator OCA-B/Pou2af1 blocks activated autoreactive T cells in the pancreas and type 1 diabetes. J Exp Med, 218(3).
  2. Joshi HR, Hill HR, Asch J, Margraf RL, Coonrod E, Durtschi J, Zhou Q, He X, Voelkerding KV, Kumnovics A (2020). CXXC5 variant in an immunodeficient patient with a progressive loss of hematopoietic cells. J Allergy Clin Immunol, 147(4), 1504-1507.e8.
  3. Joshi HR, Hill HR, Zhou Z, He X, Voelkerding KV, Kumnovics A (2020). Frontline Science: Cxxc5 expression alters cell cycle and myeloid differentiation of mouse hematopoietic stem and progenitor cells. J Leukoc Biol, 108(2), 469-484.
  4. Xiong X, Menting JG, Disotuar MM, Smith NA, Delaine CA, Ghabash G, Agrawal R, Wang X, He X, Fisher SJ, MacRaild CA, Norton RS, Gajewiak J, Forbes BE, Smith BJ, Safavi-Hemami H, Olivera B, Lawrence MC, Chou DH (2020). A structurally minimized yet fully active insulin based on cone-snail venom insulin principles. Nat Struct Mol Biol, 27(7), 615-624.
  5. 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, 295(10), 2959-2973.
  6. Zhao P, Wang P, Dong S, Zhou Z, Cao Y, Yagita H, He X, Zheng SG, Fisher SJ, Fujinami RS, Chen M (2019). Depletion of PD-1-positive cells ameliorates autoimmune disease. Nat Biomed Eng, 3(4), 292-305.
  7. Wang P, Dong S, Zhao P, He X, Chen M (2018). Direct loading of CTL epitopes onto MHC class I complexes on dendritic cell surface in vivo. Biomaterials, 182, 92-103.
  8. Wang P, Zhao P, Dong S, Xu T, He X, Chen M (2018). An Albumin-binding Polypeptide Both Targets Cytotoxic T Lymphocyte Vaccines to Lymph Nodes and Boosts Vaccine Presentation by Dendritic Cells. Theranostics, 8(1), 223-236.
  9. Zhao P, Atanackovic D, Dong S, Yagita H, He X, Chen M (2017). An Anti-Programmed Death-1 Antibody (αPD-1) Fusion Protein That Self-Assembles into a Multivalent and Functional αPD-1 Nanoparticle. Mol Pharm, 14(5), 1494-1500.
  10. Zhou Z, Reyes-Vargas E, Escobar H, Chang KY, Barker AP, Rockwood AL, Delgado JC, He X, Jensen PE (2016). 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.
  11. 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.
  12. Lee HO, He X, Mookerjee-Basu J, Zhongping D, Hua X, Nicolas E, Sulis ML, Ferrando AA, Testa JR, Kappes DJ (2015). Disregulated expression of the transcription factor ThPOK during T-cell development leads to high incidence of T-cell lymphomas. Proc Natl Acad Sci U S A, 112(25), 7773-8.
  13. Chen L, Reyes-Vargas E, Dai H, Escobar H, Rudd B, Fairbanks J, Ho A, Cusick MF, Kumnovics A, Delgado J, He X, Jensen PE (2014). Expression of the mouse MHC class Ib H2-T11 gene product, a paralog of H2-T23 (Qa-1) with shared peptide-binding specificity. J Immunol, 193(3), 1427-39.
  14. Zhou Z, He X, Jensen PE, Co-corresponding authors (2014). Molecular identification of an MHC class Ib (H2-Q9) restricted T cell receptor specific for a mouse polyomavirus peptide VP2.139. Am J Immunol, 1:3.
  15. Gu Z, Zhou W, Huang J, Yang Y, Wendlandt E, Xu H, He X, Tricot G, Zhan F (2014). Nek2 is a novel regulator of B cell development and immunological response. Biomed Res Int, 2014, 621082.
  16. Chen L, Jay DC, Fairbanks JD, He X, Jensen PE (2011). An MHC class Ib-restricted CD8+ T cell response to lymphocytic choriomeningitis virus. J Immunol, 187(12), 6463-72.
  17. He X, Park K, Wang H, Zhang Y, Hua X, Li Y, Kappes DJ (2008). CD4-CD8 Lineage Commitment is Regulated by a Silencer Element at the ThPOK Transcription-Factor Locus. Immunity, (28), 346.
  18. He X, He X, Dave VP, Zhang Y, Hua X, Nicolas E, Xu W, Roe BA, Kappes DJ (2005). The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitment. Nature, 433(7028), 826-33.
  19. He X, Woodford-Thomas TA, Johnson KG, Shah DD, Thomas ML (2002). Targeting of CD45 protein tyrosine phosphatase activity to lipid microdomains on the T cell surface inhibits TCR signaling. Eur J Immunol, 32(9), 2578-87.
  20. Feuerstein N, Firestein R, Aiyar N, He X, Murasko D, Cristofalo V (1996). Late induction of CREB/ATF binding and a concomitant increase in cAMP levels in T and B lymphocytes stimulated via the antigen receptor. J Immunol, 156(12), 4582-93.
  21. Liu T, He X, Murasko DM, Kahng KU (1996). Decreased Splenocyte Proliferation is Induced by the Serum of Bile Duct Ligation in the Rats. Surg Forum, 47, 59.
  22. He X, Le J (1995). Alternative splicing of HLA class I transcripts induced by IFN-gamma and TNF in fibroblasts: release of soluble HLA class I heavy chain and an associate protein. Cell Immunol, 162(1), 159-68.
  23. He X, Le J (1995). Alternative Splicing of HLA Class I Transcripts Induced by IFN- gamma and TNF in Fibroblasts: Release of Soluble HLA Class I Heavy Chain and an Associated Protein. Cell Immunol, 162(1): 59.
  24. Liu T, He X, Murasko DM, Kahng KU (1995). Decreased Splenocyte Proliferation and Cytokine Production in Bile Duct Ligated Rats. Surg Forum, 46, 175.
  25. Kirschmann DA, He X, Murasko DM (1994). Inhibition of macrophage-induced, antigen-specific T-cell proliferation by poly I:C role of suppressor macrophages. Immunology, 82(2), 238-43.
  26. He X, Lin YL, He QZ, Zhu YD (1985). Analysis of Experimental Conditions in the Insuction of Mouse Allospecific Cytotoxic T Lymphocytes in vitro. 5(6), 325.
  27. He X, Lin YL, He QZ, Zhu YD (1985). The Effects of Mouse Allospecific CTL on GVHR. 5(6), 331.

Review

  1. He X, Kappes DJ (2006). CD4/CD8 lineage commitment: light at the end of the tunnel? [Review]. Curr Opin Immunol, 18(2), 135-42.
  2. Kappes DJ, He X, He X (2006). Role of the transcription factor Th-POK in CD4:CD8 lineage commitment. [Review]. Immunol Rev, 209, 237-52.
  3. Kappes DJ, He X, He X (2005). CD4-CD8 lineage commitment: an inside view. [Review]. Nat Immunol, 6(8), 761-6.
  4. He X (1985). IL-2: Molecule and Function. [Review]. J Mol Biol, 7(1), 86.
  5. He X (1984). TCGF and T cell Cloning. [Review]. 4(5), 304.

Abstract

  1. He, X, Chen, L, Jay, DC, Fairbanks, J and Jensen, PE (2010). The role of MHC Ib in selecting functional CD8 T lymphocytes during acute LCMV infection [Abstract]. AAI, Baltimore.
  2. He, X, and Jensen, PE (2009). The function of zbtb7b in regulating CD4 vs. CD8 T linage commitment is evolutionarily reserved [Abstract]. AAI, Seattle.
  3. Chen, L, David, CS, Jensen PE, and He, X (2008). Identification of a New Gene in the Mouse MHC Class II Gene Cluster [Abstract]. AAI, San Diego.
  4. He, X, Reed-Loisel, ML, and PE Jensen (2008). Comparison of activation of T cells from 6C5 TCR transgenic mice in vivo and in vitro [Abstract]. Keystone Symposium, Snowbird, UT.
  5. He X, Ferrando, AA, and DJ Kappes (2007). Implication of TH-POK, a Zinc Finger Transcription Factor, in T Cell lymphomagenesis [Abstract]. FASEB Summer Research Conference, Saxtons River.
  6. Zhou Z, He X, Chen X, Jensen PE (2007). The double mutation of DRßW61A/N82A changed the MHC II-peptide complex stability and DM catalytic activity [Abstract]. 94th AAI Annual Meeting, Miami Beach.
  7. He X, Kappes DJ (2007). Implication of TH-POK, a Zing Finger Transcription Factor, in T cell lymphomagenesis [Abstract]. Keystone Symposium, Whistler.
  8. He X, Zhang Y, Kappes DJ (2005). Identification of a Zinc Transcription Factor, Th-POK, as a Critical Regulator in CD4 T lineage Commitment [Abstract]. Experimental Biology, San Diego.
  9. He X, Zhang Y, Kappes DJ (2004). Characterization of Molecular Defect in HD Mice [Abstract]. Keystone Symposium.
  10. He X, Kappes DJ (2002). Genetic Mapping of Molecular Defect in HD Mice [Abstract]. Keystone Symposium.
  11. He X, Thomas ML (2000). Targeting of CD45 Phosphatase Activity to Lipid Microdomains on T cell Surface Inhibits TCR Signaling [Abstract]. Keystone Symposium.
  12. He X, Thomas ML (1998). Generation of Transgenic Mice using Cre/loxP system [Abstract]. Cold Spring Harbor Laboratory Workshop on Conditional Genetic Technologies in the Mouse, Cold Spring Harbor.
  13. He X, Murasko DM (1995). Cytokine Production by Splenocytes of IFN-gamma Receptor Knockout Mice: Inhibition of IL-2 Production by IFN-gamma [Abstract]. 10th Immunology Congress, San Francisco.
  14. He X, Murasko DM (1995). Effects of Aging on Mitogenic Responses and Cytokine Profiles of Old and Young Mice [Abstract]. Experimental Biology, Atlanta.
  15. Le J, He X (1993). Alternative Splicing of HLA Class I Transcripts Induced by IFN-gamma and TNF in Fibroblasts: Release of Soluble HAL Class I Heavy Chain and an Associate Protein [Abstract]. Journal of Cellular Biochemistry, 17C, 58.
  16. He X, Coodly LR, Schepart BS, Heise ER (1989). Cloning of HLA-A and H-2 Qa-related I MHC Genes of Macaca fascicularis [Abstract]. Symposium: The Primate MHC: Implications for Evolution and Disease, Oegstgeest, The Netherlands.
  17. He X, Schepart BS, Coodly LR, Heise ER (1989). Expression of CyLA Class I Products in Mouse Fibroblast Cell Line L929 [Abstract]. 10th Annual Philadelphia Immunology Conference.
  18. Taylor CE, He X, Cha ME, Bright R (1989). Regulatory T Cell Respond to Immune B Cells [Abstract]. 7th International Congress of Immunology, Berlin, FRG.
  19. Schepart BS, He X, Kirschmann D, Buck D, Heise ER, Manning CH (1988). Qa-like Sequences within the Genome of the Cynomolgus Macaque, Macaca fascicularis [Abstract]. 9th Annual Philadelphia Immunology Conference, Philadelphia.
  20. He X, Taylor CE (1988). Amplifier T Cell Lines Proliferate in Response to Immune B Cells in vitro [Abstract]. 4th Annual Eastern Pennsylvania Branch of the ASM, Philadelphia.

Other

  1. Xiong X, Menting JG, Disotuar MM, Smith NA, Delaine CA, Ghabash G, Agrawal R, Wang X, He X, Fisher SJ, MacRaild CA, Norton RS, Gajewiak J, Forbes BE, Smith BJ, Safavi-Hemami H, Olivera B, Lawrence MC, Chou DH (2020). Author Correction: A structurally minimized yet fully active insulin based on cone-snail venom insulin principles. Nat Struct Mol Biol (27(7), p. 683). United States.