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Johnny J. He, PhD

Director, Center for Cancer Cell Biology, Immunology, and Infection; Professor & Discipline Chair, Microbiology and Immunology

Microbiology and Immunology Discipline

Center for Cancer Cell Biology, Immunology, and Infection

Dr. He received his MS and PhD degrees at New York University. He subsequently was a postdoctoral fellow at New York University, Rockefeller University, and Harvard Medical School. He began his independent research career at the Indiana University School of Medicine and moved to University of North Texas Health Science Center in 2011.  Dr. He joined RFUMS in 2020 as the Director of the Center for Cancer Cell Biology, Immunology, and Infection, and the Discipline Chair of Microbiology and Immunology.

RESEARCH INTERESTS

  • HIV infection and pathogenesis in astrocytes
  • Molecular mechanisms of HIV Tat protein neurotoxicity
  • Tip110 and tumorigenesis

My research focuses on the molecular biology of host-virus interactions and cancers. Viral pathogenesis and tumorigenesis are both complex and multifactorial involving numerous components and processes. It is my long-term goal to understand these components and processes and to develop therapeutic strategies targeted at these components and processes. My current ongoing major research projects are as follows:

HIV infection and pathogenesis in astrocytes.
A majority of AIDS patients experience HIV-1 infection of the central nervous system and exhibit neurologic dysfunctions. Astrocytes constitute a major population of cells in the brain, and play an indispensable role in maintaining normal brain functions. HIV infects astrocytes in vitro and in vivo, but in a restricted fashion. We have identified the HIV entry and the restricted molecular mechanisms in astrocytes. We are currently focusing on the roles of astrocytes as a latent reservoir and the underlying molecular mechanisms.

Molecular mechanisms of HIV Tat protein neurotoxicity.
In the brain, microglia/macrophages are the major target cells for HIV infection. It has generally been accepted that the neurons that are mostly affected in the brain of HIV-positive individuals are rarely infected by HIV. Therefore, a number of indirect mechanisms have been proposed for AIDS-associated neuropathogenesis. Among these is the soluble viral protein Tat. We have developed a novel inducible Tat transgenic mouse model and used this model to establish the importance and the molecular mechanisms of Tat neurotoxicity in HIV neuropathogenesis. We have continued to determine the roles of microRNAs in Tat neurotoxicity and the potential of using microRNAs as HIV neuropathogenesis biomarkers.

Tip110 and tumorigenesis.
We have spearheaded studies on HIV-1-interacting protein of 110 kDa, or Tip110 for the past 15 years. Tip110 was initially cloned during our search for Tat-interacting protein using the yeast two-hybrid screening. We have subsequently shown that this gene/protein plays important in several cellular processes, including HIV replication, pre-mRNA splicing, host gene control, stem cell biology, embryonic development, and cancer biology. Our studies have uncovered Tip110 as an indispensable and master regulator of many cellular processes and may lead to new clues of targeting this gene/protein for therapeutic development. Our current focus is on the roles of Tip110 in cancer stem cells and cancer metastasis, particularly in melanoma and glioma.

PUBLICATIONS

  1. Liu Y, Niu Y, Li L, Timani KA, He VL, Sanburns C, Xie J, He JJ. (2019) Tat expression led to increased histone 3 tri-methylation at lysine 27 and contributed to HIV latency in astrocytes through regulation of MeCP2 and Ezh2 expression. J Neurovirol. 2019 Apr 24. doi: 10.1007/s13365-019-00751-0. [Epub ahead of print] Erratum in: J Neurovirol. 2019 May 28
  2. Liu, Y., Huang, X, Timani, K. A., Broxmeyer H. E., He, J. J. (2018) Regulation of Constitutive Tip110 Expression in Human Cord Blood CD34+ Cells Through Selective Usage of the Proximal and Distal Polyadenylation Sites Within the 3′Untranslated Region. Stem Cells Dev. 27:566-576.
  3. Timani, K., Guriffy, B., Liu, Y., Mohanmad, K.S. and He, J. J. (2018) Tip110/SART3 regulates IL-8 expression and predicts the clinical outcomes in melanoma. Molecular Cancer Aug 17;17(1):124. doi: 10.1186/s12943-018-0868-z. 
  4. Liu, Y., Huang, X, Timani, K. A., Broxmeyer H. E., He, J. J. (2017) miRNA regulation of Tip110 expression and self-renewal and differentiation of human CD34+ hematopoietic cells. Oncotarget 9:4823-4832.
  5. Langford, D., Kim, B.O., Zou, W., Fan, Y., Rahimain, P., Liu, Y., and He, J. J. (2017) Doxycycline-inducible and astrocyte-specific HIV-1 Tat transgenic mice (iTat) as an HIV/neuroAIDS model. Journal of Neurovirology (2017 Nov 15. doi: 10.1007/s13365-017-0598-9. [Epub ahead of print]. 
  6. Fields JA, Metcalf J, Overk C, Adame A, Spencer B, Wrasidlo W, Florio J, Rockenstein E, He, J.J. and Masliah E. He, J. J. The anticancer drug sunitinib promotes autophagyand protects from neurotoxicity in an HIV-1 Tat model of neurodegeneration. Journal of Neurovirology. 2017 Apr;23(2):290-303. doi: 10.1007/s13365-016-0502-z. Epub 2017 Jan 19. PMID:28105557 
  7. Whitmill, A., Liu, Y., Timani, K. A., Niu, Y. and He, J. J.  Tip110 Deletion Impaired Embryonic and Stem Cell Development Involving Downregulation of Stem Cell Factors Nanog, Oct4, and Sox2. Stem Cells 35:1674-1686. 
  8. Fan, Y., Gao, X., Chen, J., Liu, Y. and He, J. J. (2016) HIV Tat Impairs Neurogenesis through Functioning As a Notch Ligand and Activation of Notch Signaling Pathway. Journal of Neuroscience 36:11362-11373. 
  9. Rahimian, P. and He, J. J. (2016) HIV-1 Tat-shortened neurite outgrowth through regulation of microRNA-132 and its target gene expression. Journal of Neuroinflammation 13:247. 
  10. Fan Y. and He, J. J. (2016) HIV-1 Tat Induces Unfolded Protein Response and Endoplasmic Reticulum Stress in Astrocytes and Causes Neurotoxicity through Glial Fibrillary Acidic Protein (GFAP) Activation and Aggregation. Journal of Biological Chemistry. 291:28819-28829. 
  11. Fan Y. and He, J. J. (2016) HIV-1 Tat Promotes Lysosomal Exocytosis in Astrocytes and Contributes to Astrocyte-mediated Tat Neurotoxicity. Journal of Biological Chemistry. 291:28830-28840. 
  12. Rahimian, P. and He, J. J. (2016) Exosome-associated release, uptake, and neurotoxicity of HIV-1 Tat protein. Journal of Neurovirology, 6:774-788. 
  13. Pyeon, D, Timani, K.A., Gulraiz, F, He, J. J., Park, I. W. (2016) Function of ubiquitin (Ub) specific protease 15 (USP15) in HIV-1 replication and viral protein degradation. Virus Research. 223:161-9. 
  14. Liu, Y., He, J. J. (2016) Role of Tip110 in the regulation of hematopoiesis. Current Opinions in Hematology. 23:325-30. 
  15. Whitmill, A., Timani, KA., Liu, Y., He, J. J. (2016) Tip110: Physical properties, primary structure, and biological functions. Life Sciences. 149:79-95. 
  16. Rahimian, P. and He, J. J. (2017) HIV/neuroAIDS biomarkers. Progress in Neurobiology, 157:117-132.
  17. Luo, X., He, J. J. (2015) Cell–cell contact viral transfer contributes to HIV infection and persistence in astrocytes. Journal of Neurovirology. 21:66-80. 
  18. Fields, J., Dumaop, W., Elueteri, S., Trejo, M., Kosberg, K., Adame, A., Spencer, B., Rockenstein, E., He, J. J. and Masliah, E. (2015) HIV-1 Tat Alters Neuronal Autophagy by Modulating Autophagosome Fusion to the Lysosome: Implications for HIV-Associated Neurocognitive Disorders. Journal of Neuroscience. 35:1921-38. 
  19. Fan, Y., Timani, K. A., He, J. J. (2015) STAT3 and Its Phosphorylation are Involved in HIV-1 Tat-Induced Transactivation of Glial Fibrillary Acidic Protein.  Current HIV Research. 13:55-63. 
  20. Luo, X., Fan, Y., Park, I. W., He, J. J. (2015) Exosomes Are Unlikely Involved in Intercellular Nef Transfer.  PLoS ONE. 10:e124436. 
  21. Fields, J., Dumaop, W., Crews, L., Adame, A., Spencer, B., Metcalf, J., He, J. J., Rockenstein, E., and Masliah E. (2015) Mechanisms of HIV-1 Tat Neurotoxicity via CDK5 Translocation and Hyper-Activation: Role in HIV-Associated Neurocognitive Disorders. Current HIV Research. 13:43-54. 
  22. Timani, K. A., Liu, Y., Fan, Y., Mohammad, K. S., He, J. J. (2015) Tip110 Regulates the Cross Talk between p53 and Hypoxia-Inducible Factor 1α under Hypoxia and Promotes Survival of Cancer Cells.  Molecular and Cellular Biology 35:2254-64. 
  23. Liu, Y., Huang, X., Timani, K. A., Broxmeyer, H. E., and He, J. J. (2015) MicroRNA-124 Targets Tip110 Expression and Regulates Hematopoiesis. Stem Cells and Development 2015 May 11. [Epub ahead of print]. 
  24. Visalli, R. J., Ziobrowski, H., Badri, K. R., He, J. J., Zhang, X., Arumugam, S. R., Zhao H. (2015) Ionic derivatives of betulinic acid exhibit antiviral activity against herpes simplex virus type-2 (HSV-2), but not HIV-1 reverse transcriptase. Bioorganic & Medicinal Chemistry Letters 25:3168-71. 
  25. Fields, J., Dumaop, W., Eleuteri, S., Campos, S., Serger, E., Trejo, M., Kosberg, K., Adame, A., Spencer, B., Rockenstein, E., He, J. J., Masliah, E. (2015) HIV-1 Tat Alters Neuronal Autophagy by Modulating Autophagosome Fusion to the Lysosome: Implications for HIV-Associated Neurocognitive Disorders. Journal of Neuroscience. 35:1921-38. 
  26. Wang, T., Chen, G., Liu, Y., Song, X., Han, C and He, J. J. (2015) Inhibition of HIV-1 entry by extracts derived from traditional Chinese medicinal herbal plants. Journal of Antivirals and Antiretrovials 7:76-82. 
  27. Liu, Y., Liu, J., Wang, Z and He, J. J. (2015) Tip110 binding to U6 small nuclear RNA and its participation in pre-mRNA splicing. Cell & Bioscience. 5:40-52. 
  28. Zhao, W., Liu, Y., and He, J. J. (2014) Tip110 Protein Binds to Unphosphorylated RNA Polymerase II and Promotes Its Phosphorylation and HIV-1 Long Terminal Repeat Transcription.  Journal of Biological Chemistry. 289:190-202. 
  29. Liu, Z., Zhao, F. and He, J. J. (2014) Hepatitis C virus (HCV) interaction with astrocytes: nonproductive infection and induction of IL-18.  Journal of Neurovirology. 20:278-293. 
  30. Park, IW, Fan, Y., Ryou, M.G., Liu, J., Green, L.A. and He, J. J. (2014) HIV-1 Nef Is Transferred from Expressing T Cells to Hepatocytic Cells through Conduits and Enhances HCV Replication PLoS ONE. 9:e99545. 
  31. Paris, J. J., Carey, A. N., Shay, C. F., Gomes, S., M., He, J. J. and McLaughlin, J. P. (2014) Effects of Conditional Central Expression of HIV-1 Tat Protein to Potentiate Cocaine-Mediated Psychostimulation and Reward Among Male Mice. Neuropsychopharmacology. 39:380-388. 
  32. Timani KA, Liu Y, Suvannasankha A, He, J. J. (2014) Regulation of ubiquitin-proteasome system-mediated Tip110 protein degradation by USP15. Int J Biochem Cell Biol. 54C:10-19. 
  33. Bagashev A, Mukerjee R, Santerre M, Del Carpio-Cano FE, Shrestha J, Wang Y, He, J. J., Sawaya BE. (2014) Involvement of miR-196a in HIV-associated neurocognitive disorders. Apoptosis. 19:1202-14. 
  34. Al-Harthi L, Buch S, Geiger JD, Gendelman HE, He, J. J., Jordan-Sciutto KL, Kolson DL, Rappaport J, Roy S, Zheng J, Fox HS (2014). Cellular Interactions and Signaling in neuroAIDS: Emerging Issues Colloquium.  J Neuroimmune Pharmacol. 9:269-76. 
  35. Timani, K. A., Liu, Y., Suvannasankha, A., He, J. J. (2014) Regulation of ubiquitin-proteasome system-mediated Tip110 protein degradation by USP15. International Journal of Biochemistry & Cell Biology. 54:10-19. 
  36. Park, I. W., Fan, Y., Luo, X., Ryou M-G., Liu, J., Green, L., He, J. J. (2014) HIV-1 Nef Is Transferred from Expressing T Cells to Hepatocytic Cells through Conduits and Enhances HCV Replication. PLoS ONE. 9(6): e99545. 
  37. Liu, Z., Zhang, X., Yu, Q., He, J. J. (2014) Exosome-associated hepatitis C virus in cell cultures and patient plasma. Biochemical and Biophysical Research Communications. 455: 218-222. 
  38. Ndjomou, J., Park, I-W, Liu, Y., Wang, M., Kao, C.C., Ridgway, N. D., and He, J. J. (2013) Inhibition of HCV Replication by Oxysterol-Binding Protein-Related Protein 4 (ORP4) through Interaction with HCV NS5B and Alteration of Lipid Droplet Formation. PLoS ONE 8: e75648. 
  39. Gao, G., Wu, X., Zhou, J., He, M., He, J. J., and Guo, D. (2013) Inhibition of HIV-1 Transcription and Replication by a Newly Identified Cyclin T1 Splice Variant. Journal of Biological Chemistry 288:14297-14309. 
  40. Park, IW and He, J. J. (2013) HIV-1 Nef-mediated T-cell activation and chemotaxis are decoupled using a HIV-1/SIVpbj1.9. chimeric nef variant. Archives of Virology 158:845- 852. 
  41. Timani, K., Liu, Y., and He, J. J. (2013) Tip110 interacts with YB-1 and regulates each other’s function. BMC Molecular Biology 14:14. 
  42. Liu, Z., and He, J. J. (2013) Cell-Cell Contact-Mediated Hepatitis C Virus (HCV) Transfer, Productive Infection, and Replication and Their Requirement for HCV Receptors. Journal of Virology 87:8545-8558. 
  43. Liu., Y, Timani, K., Ou, X., Broxmeyer, H.E., He, J. J. (2013) C-MYC Controlled TIP110 Protein Expression Regulates OCT4 mRNA Splicing in Human Embryonic Stem Cells. Stem Cells Dev. 22:689-694. 
  44. Carey, A. N., Shay, C. F., Gomes, S. M., He, J. J. and McLaughlin, J. P. (2012) HIV-1 Tat protein expression in mouse brain potentiates the behavioral psychostimulant effects of cocaine. Journal of Neuroscience 43:112-129. (IF 6.074)
  45. Liu Y, Lee MR, Timani K, He, J. J., Broxmeyer HE (2012) Tip110 Maintains Expression of Pluripotent Factors in and Pluripotency of Human Embryonic Stem Cells. Stem Cells Dev. 21:829-33. 
  46. Amet, T., Ghabril, M., Chalasani, N., Byrd, D., Hu, N., Grantham, A., Liu, Z., Qin, X., He, J.J. and Yu, Q. (2012) CD59 incorporation protects hepatitis C virus against complement‐mediated destruction. Hepatology 55:354-63. Liu, J., Henao-Mejia, H., Liu, H., Zhao, Y., and He, J. J. (2011) Translational Regulation of HIV-1 Replication by HIV-1 Rev Cellular Cofactors Sam68, eIF5A, hRIP, and DDX3. Journal of Neuroimmune Pharmacology 6: 308-321. 
  47. He, J. J. (2011) Cell Signaling Pathways and HIV-1 Therapeutics. Journal of Neuroimmune Pharmacology 6: 173-176. (IF 3.870)
  48. Liu, Y., Timani, K., Mantel, C., Fan, Y., Hangoc, G., Cooper, S., He, J. J. and Broxmeyer, H.E. (2011) TIP110/p110nrb/SART3/p110 regulation of hematopoiesis through CMYC. Blood 117:5643-51. 
  49. Chang JR, Mukerjee R, Bagashev A, Del Valle L, Chabrashvili T, Hawkins BJ, He, J. J., Sawaya BE. HIV-1 Tat Protein Promotes Neuronal Dysfunction through Disruption of MicroRNAs. Journal of Biological Chemistry. 2011 Nov 25;286(47):41125-34. 
  50. Zou, W., Wang, Z., Fan. Y. Zhou, B. Y., Yu, J., Adamson, E.D. and He, J. J. (2010) Involvement of p300 in constitutive and HIV‐1 Tat‐activated expression of glial fibrillary acidic protein in astrocytes. Glia 58:1640-1648. 
  51. Fan. Y. and He, J. J. (2010) Activation of Egr-1 Expression in Astrocytes by HIV-1 Tat: New Insights into Astrocyte-Mediated Tat Neurotoxicity. Journal of Neuroimmune Pharmacology 6: 121-129. 
  52. Park, I-W and He, J. J. (2010) HIV-1 is budded from CD4+ T lymphocytes independently of exosomes. Virology Journal 7:234.