Yoshihiro Izumiya, D.V.M., Ph.D.
Yoshihiro Izumiya D.V.M. Ph.D. and his laboratory study epigenetic gene regulation by using herpesvirus reactivation as a model system. Many viruses produce an acute infection in the human host and are then cleared by the immune system. However, other viruses, especially herpesvirus, remain in the infected person till death by producing a chronic latent infection. In latent infection, the herpesvirus hides from the immune system by silencing their own gene expression and no infectious virus can be detected during latency. The virus can be reactivated with different external stimuli and will then activate hundreds of gene expression in cascade fashion; this provides us a compelling model to study movement and regulation from “silenced chromatin” to “active chromatin” of host genome.
Dr. Izumiya’s lab is particularly interested in the epigenetic components of chromatin, including host and viral factors that interact to facilitate both the establishment and maintenance of the chromatin state as well as the molecular transitions that take place during reactivation (“chromatin remodeling”). In addition, post-translational modifications that are imparted on critical viral and host factors are also an area of research in his lab. Using a combination of genetic and biochemical approaches, they try to understand the role of host and viral protein modifications such as phosphorylation, methylation, sumoylation and ubiquitinylation on protein function and role in the viral life cycle. Their research provides insights into both the post-translational modifications and chromatin remodeling that governs viral latency and reactivation. Moreover, their research may shed new information applicable to other areas of biology, such as cancer, development and aging, where epigenetic regulation has been implicated.
Graduate Group Affiliations
Campbell M, Watanabe T, Nakano K, Davis RR, Lyu Y, Tepper CG, Durbin-Johnson B, Fujimuro M, Izumiya Y. (2018) KSHV episomes reveal dynamic chromatin loop formation with domain specific gene regulation. Nat. Commun, 9 (1): 49.
Zhou F, Shimoda M, Olney L, Lyu Y, Tran K, Jiang G, Nakano K, Davis RR, Tepper CG, Maverakis M, Campbell M, Li YP, Dandekar S, Izumiya Y. (2017) Oncolytic Reactivation of KSHV as a Therapeutic Approach for Primary Effusion Lymphoma. Mol. Cancer Ther, doi:10.1158/1535-7163. MCT-17-0041
Lyu Y, Nakano K, Davis RR, Tepper CG, Campbell M, Izumiya Y. (2017) ZIC2 is essential for maintenance of latency and is a target of an immediate-early protein during KSHV lytic reactivation. J. Virol, 91 (21); e00980-17 (selected as a JVI Spotlight Feature).
Chen CP, Lyu Y, Chuang F, Nakano K, Izumiya C, Jin D, Campbell M, Izumiya Y. (2017) Kaposi's sarcoma-associated herpesvirus hijacks RNA polymerase II to create a viral transcriptional factory. J Virol, 91 (11): e02491-16.
Wang LY, Hung CL, Chen YR, Yang JC, Wang J, Campbell M, Izumiya Y, Chen HW, Wang WC, Ann DK, Kung HJ. (2016) KDM4A coactivates E2F1 to regulate PDK-dependent metabolic switch between mitochondrial oxidation and glycolysis. Cell Rep, 16(11): 3016-3027.
Bhatt AP, Wong JP, Weinberg MS, Host KM, Giffin LC, Buijnink J, van Dijk E, Izumiya Y, Kung HJ, Temple BR, Damania B. (2016) A viral kinase mimics S6 kinase to enhance cell proliferation. Proc Natl Acad Sci U S A, 113 (28): 7876-7881.
Kim KY, Wang DH, Campbell M, Huerta SB, Shevchenko B, Izumiya C, Izumiya Y. (2015) PRMT4-mediated Arginine methylation negatively regulates retinoblastoma tumor suppressor protein and promotes E2F-1 dissociation. Mol Cell Biol, 35(1): 238-48.
Nakajima K, Zhu K, Sun YH, Hegyi B, Zeng Q, Murphy CJ, Small JV, Chen-Izu Y, Izumiya Y, Penninger JM, Zhao M. (2015) KCNJ15/Kir4.2 couples with polyamines to sense weak extracellular electric fields in galvanotaxis. Nat Commun, 6: 8532. doi: 10.1038/ncomms9532
Schreiber CA, Sakuma T, Izumiya Y, Holditch SJ, Hickey RD, Bressin RK, Basu U, Koide K, Asokan A, Ikeda Y. (2015) An siRNA Screen Identifies the U2 snRNP Spliceosome as a Host Restriction Factor for Recombinant Adeno-associated Viruses. PLoS Pathog, 11: e1005082
Campbell M, Kim KY, Chang PC, Huerta S, Shevchenko B, Wang DH, Izumiya C, Kung HJ, Izumiya Y. (2014) A lytic viral long noncoding RNA modulates the function of a latent protein. J Virol, 88(3): 1843-1848.
Campbell M, Kung HJ, Izumiya Y. (2014) Long non-coding RNA and epigenetic gene regulation of KSHV. Viruses, 6(11): 4165-4177.
Kim KY, Huerta SB, Izumiya C, Wang DH, Martinez A, Shevchenko B, Kung HJ, Campbell M, Izumiya Y. (2013) Kaposi's sarcoma-associated herpesvirus (KSHV) latency associated nuclear antigen regulates KSHV epigenome by association with histone demethylase, KDM3A. J Virol 87(12): 6782-6793.
Izumiya Y*, Kobayashi K, Kim KY, Pochampalli M, Izumiya C, Shevchenko B, Wang DH, Huerta SB, Martinez A, Campbell M, Kung HJ. (2013) Kaposi's sarcoma-associated herpesvirus K-Rta exhibits SUMO-targeting ubiquitin ligase (STUbL) like activity and is essential for viral reactivation. PLoS Pathog, 9: e1003506. *corresponding author
Hsia DA, Tepper CG, Pochampalli MR, Hsia EY, Izumiya C, Huerta SB, Wright ME, Chen HW, Kung HJ, Izumiya Y. (2010) KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation. Proc Natl Acad Sci U S A, 107(21): 9671-9676
- American Cancer Society Research Scholar (2013)
- 1st Place Poster Award, UC Davis Cancer Center Symposium (2011)
- Award for Excellence in Postdoctoral Research at UC Davis (2005)
- Universitywide AIDS Research Program Postdoctoral Awards (2003-2005)
- Plenary Honors Japanese Veterinary Medical Science (2003)
- Uehara Memorial Postdoctoral Fellowship (2002)
- Research Fellowships for Young Scientists of the Japan Society for Promotion of Science (1998-2001)
- Mel Campbell, Associate Project Scientist
- Yuanzhi Lyu, Postdoctoral fellow
- Chie Izumiya, Assistant Project Scientist
- Jin Di, Graduate Student
- Kazushi Nakano, Visiting Researcher