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Jun Yang, MD, PhD
Jun Yang, MD, PhD

Jun Yang, MD, PhD

Assistant Member, St. Jude Faculty

Departments

Education

PhD - The Institute of Cancer Research, Sutton, UK
MS 
- National Institute for Control of Pharmaceutical and Biological Products, Beijing, China
MD
 - Qingdao Medical College, China

Research Interests

  • The role of histone modifiers in cancer
  • Rational combination therapy
  • Hypoxia signaling pathway and angiogenesis
  • miRNA function in cancer
  • Drug discovery

The genetic abnormalities that drive tumorigenesis are usually coupled with epigenetic alterations such as DNA methylation, aberrant histone modification and non-coding RNA expression, which may help oncogenic drivers accelerate cancer progression, metastasis and drug resistance. The next generation sequencing data have identified recurrent somatic mutations in multiple genes involving histone modifications and chromatin remodeling, providing direct evidence for the importance of epigenetic modifiers in cancer. In addition, deregulated gene expression of epigenetic modifiers is also commonly found in cancers. Our laboratory focuses on how epigenetics collaborate with oncogenic drivers during pathogenesis and development of specific small molecule inhibitors for precision medicine. Currently, we are using a variety of molecular, cellular, pharmacologic approaches and in vivo mouse models to dissect the functions of histone demethylases and other histone modifiers in pediatric cancers. We are also collaborating with Department of Chemical Biology and Therapeutics to screen histone demethylase inhibitors for cancer treatment.

Selected Publications

D'Oto A, Fang J, Jin H, Xu B, Singh S, Mullasseril A, Jones V, Abu-Zaid A, von Buttlar X, Cooke B, Hu D, Shohet J, Murphy AJ, Davidoff AM, Yang J. KDM6B promotes activation of the oncogenic CDK4/6-pRB-E2F pathway by maintaining enhancer activity in MYCN-amplified neuroblastoma. Nat Communications Dec 10;12(1):7204, 2021.

Singh S, Quarni W, Goralski M, Wan S, Jin H, Van de Velde LA, Fang J, Wu Q, Abu-Zaid A, Wang T, Singh R, Craft D, Fan Y, Confer T, Johnson M, Akers WJ, Wang R, Murray PJ, Thomas PG, Nijhawan D, Davidoff AM, Yang J. Targeting the spliceosome through RBM39 degradation results in exceptional responses in high-risk neuroblastoma models. Science Advances Nov 19;7(47):eabj5405, 2021.

Wu Q, Lin W, Li ZM, Rankovic Z, White SW, Chen T, Yang J. A protocol for high-throughput screening of histone lysine demethylase 4 inhibitors using TR-FRET assay. STAR Protoc Sep 17;2(3):100702, 2021. doi: 10.1016/j.xpro.2021.100702. eCollection 2021 Sep 17

Singh S, Abu-Zaid A, Lin W, Low J, Abdolvahabi A, Jin H, Wu Q, Cooke B, Fang J, Bowling J, Vaithiyalingam S, Currier D, Yun MK, Fernando DM, Maier J, Tillman H, Bulsara P, Lu Z, Das S, Shelat A, Li Z, Young B, Lee R, Rankovic Z, Murphy AJ, White SW, Davidoff AM, Chen T, Yang J. 17-DMAG dually inhibits Hsp90 and histone lysine demethylases in alveolar rhabdomyosarcoma. iScience Jan 22;24(1):101996, 2021.

Williams J, Xu B, Putnam D, Thrasher A, Li C, Yang J, Chen X. MethylationToActivity: a deep-learning framework that reveals promoter activity landscapes from DNA methylomes in individual tumors. Genome Biology Jan 19;22(1):24, 2021.

Slavish PJ, Chi L, Yun MK, Tsurkan L, Martinez NE, Jonchere B, Chai SC, Connelly M, Waddell MB, Das S, Neale G, Li Z, Shadrick WR, Olsen RR, Freeman KW, Low JA, Price JE, Young BM, Bharatham N, Boyd VA, Yang J, Lee RE, Morfouace M, Roussel MF, Chen T, Savic D, Guy RK, White SW, Shelat AA, Potter PM. Bromodomain-Selective BET Inhibitors Are Potent Antitumor Agents against MYC-Driven Pediatric Cancer. Cancer Research Sep 1;80(17):3507-3518, 2020.

Wang T, Gnanaprakasam JNR, Chen X, Kang S, Xu X, Sun H, Liu L, Rodgers H, Miller E, Cassel TA, Sun Q, Vicente-Muñoz S, Warmoes MO, Lin P, Piedra-Quintero ZL, Guerau-de-Arellano M, Cassady KA, Zheng SG, Yang J, Lane AN, Song X, Fan TW, Wang R. Inosine is an alternative carbon source for CD8+-T-cell function under glucose restriction. Nature Metabolism Jul;2(7):635-647, 2020. doi: 10.1038/s42255-020-0219-4

Hu D, Jablonowski C, Cheng PH, AlTahan A, Li C, Wang Y, Palmer L, Lan C, Sun B, Abu-Zaid A, Fan Y, Brimble M, Gamboa NT, Kumbhar RC, Yanishevski D, Miller KM, Kang G, Zambetti GP, Chen T, Yan Q, Davidoff AM, Yang J. KDM5A Regulates a Translational Program that Controls p53 Protein Expression. iScience Nov 30;9:84-100, 2018. 

Lian G, Gnanaprakasam JR, Wang T, Wu R, Chen X, Liu L, Shen Y, Yang M, Yang J, Chen Y, Vasiliou V, Cassel TA, Green DR, Liu Y, Fan TW, Wang R. Glutathione de novo synthesis but not recycling process coordinates with glutamine catabolism to control redox homeostasis and directs murine T cell differentiation. Elife Sep 10;7, 2018. doi: 10.7554/eLife.36158.

Feng H, Tillman H, Wu G, Davidoff AM, Yang J. Frequent epigenetic alterations in polycomb repressive complex 2 in osteosarcoma cell lines. Oncotarget Jun 5;9(43):27087-27091, 2018. 

Wang T, Liu L, Chen X, Shen Y, Lian G, Shah N, Davidoff AM, Yang J*, Wang R*. MYCN drives glutaminolysis in neuroblastoma and confers sensitivity to an ROS augmenting agent. Cell Death Dis Feb 14;9(2):220, 2018. (*corresponding author)

Yang J, Harris AL, Davidoff AM. Hypoxia and Hormone-Mediated Pathways Converge at the Histone Demethylase KDM4B in Cancer. Int J Mol Sci Jan 13;19(1), 2018. doi: 10.3390/ijms19010240  

Yang J*, Milasta S, Hu D, AlTahan AM, Interiano RB, Zhou J, Davidson J, Low J, Lin W, Bao J, Goh P, Nathwani AC, Wang R, Wang Y, Ong SS, Boyd VA, Young B, Das S, Shelat A, Wu Y, Li Z, Zheng JJ, Mishra A, Cheng Y, Qu C, Peng J, Green DR, White S, Guy RK, Chen T, Davidoff AM. Targeting Histone Demethylases in MYC-Driven Neuroblastomas with Ciclopirox. Cancer Research Sep 1;77(17):4626-4638, 2017. (*corresponding author)

Tian Y, Huang W, Yang J, Wen Z, Geng Y, Zhao C, Zhang H, Wang Y. Systematic identification of hepatitis E virus ORF2 interactome reveals that TMEM134 engages in ORF2-mediated NF-κB pathway. Virus Res Jan 15;228:102-108, 2017. 

D'Oto A, Tian QW, Davidoff AM, Yang J. Histone demethylases and their roles in cancer epigenetics. J Med Oncol Ther 1(2):34-40, 2016.

Show More

Yang J*, AlTahan A, Jones D, Buffa FM, Bridgesa E, Interiano RB, Qu C, Vogt N, Li J, Baban D, Ragoussis J, Nicholson RI, Davidoff  AM, Harris AL. Estrogen receptor alpha directly regulates the hypoxia-inducible factor 1 pathway associated with anti-estrogen response in breast cancer. Proc Natl Acad Sci U S A 112(49):15172-15177,2015.  *corresponding author

Yang J, AlTahan A, Hu D, Wang Y, Cheng PH, Morton CL, Qu C, Nathwani AC, Shohet JM, Fotsis T, Koster J, Versteeg R, Okada H, Harris AL, and Andrew M. DavidoffThe role of histone demethylase KDM4B in Myc signaling in neuroblastoma. Journal of National Cancer Institute 107(6):1-9, 2015.
Comments on JNCI, 107(6): Expanding MYCN’s Reach in Oncogenic Transcription.

Interiano RB, Yang J, Harris AL, Davidoff AM. Seven In Absentia Homolog 2 (SIAH2) downregulation is associated with tamoxifen resistance in MCF-7 breast cancer cells. Journal of Surgery Research 190:203-209, 2014.

Zhou Y, Geng Y, Yang J, Zhao C, Harrison TJ, Wang Y. Hepatitis E Virus open reading frame 3 protein interacts with porcine liver-specific plasminogen and α2-antiplasmin. Journal of Medical Virology 86:487-495, 2014.

Geng Y, Yang J, Huang W, Harrison TJ, Zhou Y, Wen Z, Wang Y. Virus Host Protein interaction network analysis reveals that the HEV ORF3 protein may interrupt the blood coagulation process. PLoS One 8:e56320, 2013.

Yang J, Staples O, Thomas LW, et al.  Human CHCHD4 mitochondrial proteins regulate cellular oxygen consumption rate and metabolism and provide a critical role in hypoxia signaling and tumor progression. Journal of Clinical Investigation 122:600-611, 2012. (Cover featured)

Briston T, Yang J, Ashcroft M. HIF-1α localization with mitochondria: a new role for an old favorite? Cell Cycle 10:4170-4171, 2011.

Ahmed A, Yang J, Maya-Mendoza A, Jackson DA, Ashcroft M. Pharmacological activation of a novel p53-dependent S-phase checkpoint involving CHK-1. Cell Death and Diseases 2:e160, 2011.

Yang J, Jubb AM, Pike L, Buffa FM, Turley H, Baban D, Leek R, Gatter KC, Ragoussis J, Harris AL. The histone demethylase JMJD2B is regulated by estrogen receptor alpha and hypoxia, and is a key mediator of estrogen induced growth. Cancer Research 70:6456-6466, 2010. (Cover featured)

Lu M, Yang J, Ren Z, Sabui S, Espejo A, Bedford MT, Jacobson RH, Jeruzalmi D, McMurray JS, Chen X. Crystal structure of the three tandem FF domains of the transcription elongation regulator CA150. Journal of Molecular Biology 393:397-408, 2009.

Yang J, Ledaki I, Turley H, Gatter KC, Montero JC, Li JL, Harris AL. Role of hypoxia-inducible factors in epigenetic regulation via histone demethylases. Annals of the New York Academy Sciences 1177:185-197, 2009.

Yang J, Ahmed A, Ashcroft M. Activation of a unique p53-dependent DNA damage response. Cell Cycle 8(10):1630-1632, 2009.

Yang J, Ahmed A, Poon E, Perusinghe N,  de Haven Brandon A, Box G, Valenti M, Eccles S, Ashcroft M.  Small molecule activation of p53 blocks HIF-1α and VEGF expression in vivo and leads to tumor cell apoptosis in normoxia and hypoxia. Molecular and Cellular Biology 29:2243-2253, 2009.

Sutton KM, Chau, NM, Cook S, Pouyssegur J, Ahmed A, Perusinghe N, Le Flock R, Yang J, Ashcroft M. Selective inhibition of MEK1/2 reveals a differential requirement for ERK1/2 signalling in the regulation of HIF-1 in response to hypoxia and IGF-1. Oncogene 26:3920-3929, 2007.

Wary KK, Thakker GD, Humtsoe JO, Yang J. Analysis of VEGF-responsive genes involved in the activation of endothelial cells. Molecular Cancer 2:1-12, 2003.

Humtsoe JO, Feng S, Thakker GD, Yang J, Hong J, and Wary KK. Regulation of cell-cell interactions by phosphatidic acid phosphatase 2b/VCIP. EMBO Journal 22:1539-1554, 2003.

Wang YC, Lin JX, Zhang HY, Yang J, Li HM. Studies of S antigen variants of hepatitis B virus. Chinese Biological Products 1:1-3, 2000.

Yang J, Wang YC, Zhang HY, and Li HM. The detection of TT virus and partial nucleotide sequence comparison. Chinese Journal of Microbiology and Immunology 1:13-1, 2000.

Yang J, Zhang HY, Wang YC, Mao QY, and Li HM. Partial cloning and analysis of a new hepatitis E virus. Chinese Journal of Microbiology and Immunology 4:293-299, 2000.

Yang J, Zhang HY, Wang YC, Mao QY, and Li HM. Partial sequence comparison of three sporadic hepatitis E variants. Virologica Sinica 4:203-208, 2000.

Yang J, Zhang HY, Wang YC, Lan HY, and Li HM. The distribution of TT virus genotypes among the Chinese blood donors. Chinese Journal of Preventive Medicine 5:371-377, 2000.

Last update: February 2022

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