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

Jun Yang, MD, PhD

Associate Member, St. Jude Faculty



PhD - The Institute of Cancer Research, Sutton, UK
- National Institute for Control of Pharmaceutical and Biological Products, Beijing, China
 - 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

Abu-Zaid A, Fang J, Jin H, Singh S, Pichavaram P, Wu Q, Tillman H, Janke L, Rosikiewicz W, Xu B, Van De Velde LA, Guo Y, Li Y, Shendy NAM, Delahunty IM, Rankovic Z, Chen T, Chen X, Freeman KW, Hatley ME, Durbin AD, Murray PJ, Murphy AJ, Thomas PG, Davidoff AM, Yang J. Histone lysine demethylase 4 family proteins maintain the transcriptional program and adrenergic cellular state of MYCN-amplified neuroblastoma. Cell Rep MedMar 19;5(3):101468, 2024 . doi: 10.1016/j.xcrm.2024.101468. 

Jablonowski CM, Quarni W, Singh S, Tan H, Bostanthirige DH, Jin H, Fang J, Chang TC, Finkelstein D, Cho JH, Hu D, Pagala V, Sakurada SM, Pruett-Miller SM, Wang R, Murphy A, Freeman K, Peng J, Davidoff AM, Wu G, Yang J. Metabolic reprogramming of cancer cells by JMJD6-mediated pre-mRNA splicing associated with therapeutic response to splicing inhibitor. Elife. Mar 15;12, 2024 . doi: 10.7554/eLife.90993. 

Yang J. Approval of DFMO for high-risk neuroblastoma patients demonstrates a step of success to target MYC pathway. Br J Cancer. Mar;130(4):513-516, 2024. doi: 10.1038/s41416-024-02599-6

Pichavaram P, Jablonowski CM, Fang J, Fleming AM, Gil HJ, Boghossian AS, Rees MG, Ronan MM, Roth JA, Morton CL, Zambetti GP, Davidoff AM, Yang J, Murphy AJ. Oncogenic cells of renal embryonic lineage sensitive to the small molecule inhibitor QC6352 display depletion of KDM4 levels and disruption of ribosome biogenesis. Molecular Cancer Therapeutics Nov 18, 2023. doi: 10.1158/1535-7163.MCT-23-0312.

Lee HM, Wright WC, Pan M, Low J, Currier D, Fang J, Singh S, Nance S, Delahunty I, Kim Y, Chapple RH, Zhang Y, Liu X, Steele JA, Qi J, Pruett-Miller SM, Easton J, Chen T, Yang J, Durbin AD, Geeleher P. A CRISPR-drug perturbational map for identifying compounds to combine with commonly used chemotherapeutics. Nature Communications Nov 13;14(1):7332, 2023. doi: 10.1038/s41467-023-43134-0. (co-corresponding author) 

Gnanaprakasam JNR, Kushwaha B, Liu L, Chen X, Kang S, Wang T, Cassel TA, Adams CM, Higashi RM, Scott DA, Xin G, Li Z, Yang J, Lane AN, Fan TW, Zhang J, Wang R. Asparagine restriction enhances CD8+ T cell metabolic fitness and antitumoral functionality through an NRF2-dependent stress response. Nature Metabolism Aug;5(8):1423-1439, 2023. doi: 10.1038/s42255-023-00856-1 

Fang J, Singh S, Cheng C, Natarajan S, Sheppard H, Abu-Zaid A, Durbin AD, Lee HW, Wu Q, Steele J, Connelly JP, Jin H, Chen W, Fan Y, Pruett-Miller SM, Rehg JE, Koo SC, Santiago T, Emmons J, Cairo S, Wang R, Glazer ES, Murphy AJ, Chen T, Davidoff AM, Armengol C, Easton J, Chen X, Yang J. Genome-wide mapping of cancer dependency genes and genetic modifiers of chemotherapy in high-risk hepatoblastoma. Nature Communications Jul 6;14(1):4003, 2023. doi: 10.1038/s41467-023-39717-6 

Rana M, Kansal RG, Bisunke B, Fang J, Shibata D, Bajwa A, Yang J, Glazer ES. Bromo- and Extra-Terminal Domain Inhibitors Induce Mitochondrial Stress in Pancreatic Ductal Adenocarcinoma. Molecular Cancer Therapeutics Jun 8, 2023. doi: 10.1158/1535-7163.MCT-23-0149

Yang J, Davidoff AM. Remarkable Synergy When Combining EZH2 Inhibitors with YM155 Is H3K27me3-Independent. Cancers (Basel) Dec 29;15(1), 2022. doi: 10.3390/cancers15010208

Wu Q, Young B, Wang Y, Davidoff AM, Rankovic Z, Yang J. Recent Advances with KDM4 Inhibitors and Potential Applications. Journal of Medicinal Chemistry Jul 28;65(14):9564-9579, 2022. doi: 10.1021/acs.jmedchem.2c00680

Singh S, Abu-Zaid A, Jin H, Fang J, Wu Q, Wang T, Feng H, Quarni W, Shao Y, Maxham L, Abdolvahabi A, Yun MK, Vaithiyalingam S, Tan H, Bowling J, Honnell V, Young B, Guo Y, Bajpai R, Pruett-Miller SM, Grosveld GC, Hatley M, Xu B, Fan Y, Wu G, Chen EY, Chen T, Lewis PW, Rankovic Z, Li Y, Murphy AJ, Easton J, Peng J, Chen X, Wang R, White SW, Davidoff AM, Yang J. Targeting KDM4 for treating PAX3-FOXO1-driven alveolar rhabdomyosarcoma. Science Translational Medicine Jul 13;14(653):eabq2096, 2022. doi: 10.1126/scitranslmed.abq2096

Hou R, Yu Y, Sluter MN, Li L, Hao J, Fang J, Yang J, Jiang J. Targeting EP2 receptor with multifaceted mechanisms for high-risk neuroblastoma. Cell Reports Jun 21;39(12):111000, 2022. doi: 10.1016/j.celrep.2022.111000 

Chen X, Sunkel B, Wang M, Kang S, Wang T, Gnanaprakasam JNR, Liu L, Cassel TA, Scott DA, Muñoz-Cabello AM, Lopez-Barneo J, Yang J, Lane AN, Xin G, Stanton BZ, Fan TW, Wang R. Succinate dehydrogenase/complex II is critical for metabolic and epigenetic regulation of T cell proliferation and inflammation. Sci Immunol Apr 29;7(70):eabm8161, 2022. doi: 10.1126/sciimmunol.abm8161

Jablonowski CM, Gil HJ, Pinto EM, Pichavaram P, Fleming AM, Clay MR, Hu D, Morton CL, Pruett-Miller SM, Hansen BS, Chen X, Jones KMD, Liu Y, Ma X, Yang J, Davidoff AM, Zambetti GP, Murphy AJ. TERT Expression in Wilms Tumor Is Regulated by Promoter Mutation or Hypermethylation, WT1, and N-MYC. Cancers (Basel) Mar 25;14(7), 2022. doi: 10.3390/cancers14071655

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

Show More

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.

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: March 2024