Achievements and Publications

Achievements

A major part of our publications focuses on the discovery and characterization of the uncharted area of cancer genetics. I pioneered an integrative bioinformatics approach that utilizes multidimensional genomic datasets to identify driver gene fusions in solid tumors. Our methodologies have resulted in notable discoveries, such as identifying NFE2 rearrangements in lung cancer (published in Nature Biotechnology, 2009, and patented as US9938582) and the first oncogenic KRAS fusions in a rare subset of metastatic prostate cancers (published in Cancer Discovery, 2011, also patented as US9938582 which has been licensed to Gen-probe). Our laboratory has further identified three recurrent gene fusions in breast cancer. These are currently the only canonical gene fusions recognized in major breast cancer subtypes.

1. Wang XS, Prensner JR, Chen G, Cao Q, Han B, Dhanasekaran SM, Ponnala R, Cao X, Varambally S, Thomas DG, Giordano TJ, Beer DG, Palanisamy N, Sartor MA, Omenn GS, Chinnaiyan AM. An integrative approach to reveal driver gene fusions from paired-end sequencing data in cancer. Nature Biotechnology. 2009 27:1005-1011. Read More.

2. Wang XS, Shankar S, Dhanasekaran SM*, Ateeq B, Prensner JR, Yocum AK, Pflueger D, Jing X, Fries DF, Han B, Li Yong, Cao Q, Cao X, Maher CA, Kumar SC, Demichelis F, Tewari AK, Kuefer R, Omenn GS, Palanisamy S, Rubin MA, Varambally S, Chinnaiyan AM. Characterization of KRAS Rearrangements in Metastatic Prostate Cancer. Cancer Discovery. 2011 1:35-43. Read More.

Our key achievements in breast cancer genetics include: 1) Our lab identified the first gene fusion involving the estrogen receptor, ESR1-CCDC170, which confers endocrine resistance in a significant subset of ER+ breast cancers (Nature Commun. 2014). This fusion remains the most important gene fusion reported in luminal breast cancer, which can be potentially targeted by HER2 inhibitors (Breast Cancer Res. 2020, Patent Application PCT/US2021/029086), and clinical significance is supported by several subsequent clinical studies. 2) Our lab also identified a novel BCL2L14-ETV6 fusion specific to triple-negative breast cancer (TNBC). This fusion is preferentially detected in more aggressive TNBC forms and promotes epithelial-mesenchymal transition and paclitaxel resistance (PNAS 2020, Patent application PCT/US21/19846). Supported by a DOD breakthrough award, our team is exploring the potential of BCL2L14-ETV6 as a predictive genetic marker for combining β-catenin inhibitors with immunotherapy in TNBC. 3) We also identified a novel RAD51AP1-DYRK4 fusion transcript that underpins the metastasis-prone behaviors of more aggressive luminal breast cancer forms, conferring vulnerability to MEK inhibitors (Clinical Cancer Res. 2021, Patent Application PCT/US21/040463).

1. Veeraraghavan J, Tan Y, Cao XX, Kim JA, Wang X, Chamness GC, Maiti SN, Cooper LJN, Edwards DP, Contreras A, Hilsenbeck SG, Chang EC, Schiff R, Wang XS#. Recurrent ESR1-CCDC170 rearrangements in an aggressive subset of estrogen-receptor positive breast cancers. Nature Communications. 2014 5:4577. Read More.

2. Lee S, Hu Y, Loo SK, Tan Y, Bhargava R, Lewis MT, Wang XS#. Landscape analysis of adjacent gene rearrangements reveals BCL2L14-ETV6 gene fusions in more aggressive triple-negative breast cancer. Proc Natl Acad Sci U S A. 2020 18:9912-9921. Read More.

3. Li Li, Ling Lin, Jamunarani Veeraraghavan, Yiheng Hu, Xian Wang, Sanghoon Lee, Ying Tan, Rachel Schiff, Xiao-Song Wang#. Therapeutic role of recurrent ESR1-CCDC170 gene fusions in breast cancer endocrine resistance. Breast Cancer Research. 2020 22:84. Read More.

In addition to gene fusions, we also identified a novel non-traditional RAD51AP1-DYRK4 chimera underpinning the metastasis-prone behaviors of more aggressive breast cancer forms that lack well-defined targets for effective intervention. By conferring selective vulnerability to MEK inhibitors, RAD51AP1-DYRK4 may be an Achilles heel of these deadly tumors that otherwise could have a devastating clinical outcome.

4. Liu CC, Veeraraghavan J, Tan Y, Kim JA, Wang X, Loo SK, Lee S, Hu Y, and Wang XS#. A novel neoplastic fusion transcript, RAD51AP1-DYRK4, confers sensitivity to the MEK inhibitor trametinib in aggressive breast cancers. Clinical Cancer Research. 2021 3:785-798. Read More.

5. Loo SK, Yates ME, Yang S, Oesterreich S, Lee AV, Wang XS#. Fusion-associated carcinomas of the breast: Diagnostic, prognostic, and therapeutic significance. Genes Chromosomes Cancer. 2022 61(5):261-273. Read More.

Another research focus of our lab is to identify actionable kinase targets in aggressive breast cancers. First, we identified TLK2 as a key kinase target that is frequently amplified in aggressive luminal breast cancers. TLK2 promotes breast cancer invasiveness, modulates G1/S cell cycle transition, impairs G2/M checkpoint, and predicts worse clinical outcome (Nature Communications. 2016, Mol Cancer Res. 2016). Second, our lab identified a serine-threonine kinase target NLK and revealed its key role in breast cancer endocrine resistance. We then went on to identify a dual p38 and NLK inhibitor and evaluated its therapeutic value in preclinical models of endocrine-resistant breast cancers (Clinical Cancer Res. 2021).

1. Wang X, Veeraraghavan J, Liu C, Cao X, Qin L, Kim J, Tan Y, Loo S, … Mitchell T, Li S, Ellis M, Hilsenbeck SG, Schiff R, Wang XS#. Therapeutic targeting of nemo-like kinase in primary and acquired endocrine-resistant breast cancer. Clinical Cancer Research. 2021 Feb 4. Read More.

2. Kim JA, Tan Y, Wang X, Cao X, Veeraraghavan J, Liang Y, Edwards DP, Huang S, Pan X, Li K, Schiff R. and Wang XS#. Comprehensive functional analysis of the tousled-like kinase 2 frequently amplified in aggressive luminal breast cancers. Nature Communications. 2016 7:12991. Read More.

3. Kim JA, Anurag M, Veeraraghavan J, Schiff R, Li K, Wang XS#. Amplification of TLK2 Induces Genomic Instability via Impairing the G2/M Checkpoint. Mol Cancer Res. 2016 14:920-927. Read More.

4. Fan Y, Ge N, Wang XS, Sun W, Mao R, Bu W, Creighton CJ, Zheng P, Vasudevan S, An L, Yang J, Zhao YJ, Zhang H, Li XN, Rao PH, Leung E, Lu YJ, Gray JW, Schiff R, Hilsenbeck SG, Osborne CK, Yang J, Zhang H. Amplification and overexpression of MAP3K3 gene in human breast cancer promotes formation and survival of breast cancer cells. The Journal of Pathology. 2014 232:75-86. Read More.

We developed a new class of transparent and interpretable machine learning methods called integral genomic signature analyses (iGenSig: Nature Communications, 2022, iGenSig-Rx: BMC Bioinformatics 2024, Patent Application PCT/US2021/072950). We are now advancing this with iGenSig-AI, an advanced mechanism-driven AI model that fuses our established integral genomic signature framework with biologically informed artificial intelligence. This model leverages integral genomic signatures for enhanced cross-dataset performance, employing transfer learning techniques to identify biologically relevant transcriptional and regulatory mechanisms driving therapeutic sensitivity and resistance. By enabling high-fidelity, mechanism-based AI simulated drug screening, our goal is to create clinical-grade AI models that deliver comprehensive treatment decision support and unleash the power of low-cost omics-based precision oncology. Furthermore, we developed an Indepth-Pathway tool for deep functional assessment of the pathways enriched in an integral genomic signature as well as based on single cell sequencing data (Briefings in Bioinformatics. 2020, Bioinformatics 2023).

1. Wang XS#, Lee S, Zhang H, Tang G, Wang Y. An integral genomic signature approach for tailored cancer therapy using genome-wide sequencing data. Nature Communications. 2022 13(1):2936. Read More.

2. Xu Chi, Maureen A. Sartor, Sanghoon Lee, Meenakshi Anurag, Snehal Patil, Pelle Hall, Matthew Wexler, Xiaosong Wang#. Universal Concept Signature Analysis: Genome-Wide Quantification of New Biological and Pathological Functions of Genes and Pathways. Briefings in Bioinformatics, Oct. bbz093. Read More.

3. Lee S, Deng L, Wang Y, Wang K, Sartor MA, Wang XS#. IndepthPathway: an integrated tool for in-depth pathway enrichment analysis based on single-cell sequencing data. Bioinformatics. 2023 Jun 1;39(6): btad325 Read More.

Our achievements on computational immunogenomics focus on discovering precision genomic biomarkers for cancer immunotherapy. Our key achievements in this area include: 1) Intragenic Rearrangement Burden: Identified as a predictive biomarker for immune checkpoint inhibition response in TMB-low tumor entities (Cancer Immunology Res., 2024, Featured article). Funded by a DOD Breakthrough Award, we are developing a WGS-based IGR burden assay for predicting ICB response in TNBC. 2) Tumor-Associated Antigen Burden: Most recently, our lab discovered TAA burden as predictors of ICB response in PD-L1 negative tumors, challenging existing paradigms and revealing a novel immunoediting theory of TAAs (Cancer Immunology Res., 2024, accepted). We also developed an innovative approach called HEPA-PARSE, for high-throughput identification of tumor associated antigens (TAAs) (Cancer Research 2012).

1. Wang Y, Hu MH, Finn OJ, Wang XS#. Tumor-Associated Antigen Burden Correlates with Immune Checkpoint Blockade Benefit in Tumors with Low Levels of T-cell Exhaustion. Cancer Immunology Research. 2024 Aug 13. Read More.

1. Zhang H, Lee S, Muthakana R, Lu B, Boone DN, Lee D, Wang XS#. Associations of intragenic rearrangement burden with immune cell infiltration and response to immune checkpoint blockade in cancer. Cancer Immunology Research. 2024. Feb. OF0-9 Read More.

2. Xu QW, Zhao W, Wang Y, Sartor MA, Han DM, Deng JX, Ponnala R, Yang JY, Zhang QY, Liao GQ, Qu YM, Li L, Liu FF, Zhao HM, Yin YH, Chen WF, Zhang Y#, Wang XS#. An integrated genome-wide approach to discover tumor specific antigens as potential immunological and clinical targets in cancer. Cancer Research. 2012 72:6351-61. Read More.

3. Wang XS, Zhao H, Xu Q, Jin W, Liu C, Zhang H, Huang Z, Zhang X, Zhang Y, Xin D, Simpson AJ, Old LJ, Na Y, Zhao Y, Chen W. HPtaa database-potential target genes for clinical diagnosis and immunotherapy of human carcinoma. Nucleic Acids Research. 2006 34: D607-12. Read More.

Our pioneering work in biomarker discovery is highlighted by the identification of two urinary biomarkers, UCA1 and UPK3A (Clinical Cancer Research, 2006 and Urology, 2010). Notably, I am the first to clone and name the UCA1 gene, a well-known urinary biomarker and long non-coding RNA (lncRNA). Recent reviews emphasize UCA1 as one of the most frequently reported urinary markers with outstanding diagnostic performance. A meta-analysis of seven studies further supports its efficacy, demonstrating a sensitivity of 84% and specificity of 87% in detecting bladder cancer (Medicine 100:e24805, 2021). Additionally, UCA1 has been established as a pivotal oncogene in the tumorigenesis of various cancer types and has been the focus of extensive global research.

1. Wang XS, Zhang Z, Wang HC, Cai JL, Xu QW, Li MQ, Chen YC, Qian XP, Lu TJ, Yu LZ, Zhang Y, Xin DQ, Na YQ, Chen WF. Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma. Clinical Cancer Research. 2006 12:4851-8. Read More.

2. Lai YQ, Ye JX, Chen J, Zhang LB, Wasi LJ, He ZS, Zhou LQ, …Gui YT, Cai ZM, Wang XS#, Guan ZC#. UPK3A：A Promising Novel Urinary Marker for the Detection of Bladder Cancer. Urology. 2010 76:51. Read more.

Our research also uncovered significant epigenetic targets in therapy-resistant breast cancer. Initially, he identified an epigenetically activated oncogene, HORMAD1, which exhibits preferential expression in basal-like breast cancer. Using preclinical mouse models, our lab investigated its role in sensitizing tumors to rucaparib (Oncotarget, 2018). This discovery has been substantiated by multiple recent studies. Furthermore, we discovered that SYCP2, a meiotic protein, confers resistance to DNA-damaging agents in breast cancer (Nature Communications, 2024). Additionally, we identified MYST3 as a novel epigenetic activator of ERα, frequently amplified in breast cancer (Oncogene, 2016), and MAP3K3, a kinase target implicated in breast carcinogenesis and resistance to cytotoxic chemotherapy (Journal of Pathology, 2014). These three epigenetic targets have been rigorously validated through experimental studies conducted by our collaborators.

1. Yumin Wang, Boya Gao, Luyuan Zhang, … Lee Zou, Leif William Ellisen, Xiao-song Wang, Li Lan. Meiotic Protein SYCP2 Confers Resistance to DNA-Damaging Agents through R-Loop-Mediated DNA Repair. Nature Communications. 2024. Feb 21;15(1):1568. Read More.

1. Wang X, Tan Y, Cao X, Kim JA, Chen T, Hu Y, Wexler M, Wang XS#. Epigenetic activation of HORMAD1 in basal-like breast cancer: role in Rucaparib sensitivity. Oncotarget. 2018 10;9(53):30115-30127. Read More.

2. Yu L, Liang Y, Cao X, Wang X, Gao H, Lin SY, Schiff R, Wang XS#, Li K#. Identification of MYST3 as a novel epigenetic activator of ERα frequently amplified in breast cancer. Oncogene. 2016 10.1038 /onc.2016.433. Read More.

Publications

Lawal B., Wang Y., Lotfinejad P., Sharma R., Yang C., Annasamudram A., Wang X-S#.
NFATC2 target gene signature correlates with immune checkpoint blockade resistance in melanoma,
Am J Cancer Res 2025 Jan 15;15(1):311–321
Yates, M., Li, Z., Li, Y., Guzolik, H., Wang, X-S., Liu, T., Hooda, J., Atkinson, J., Lee, A., Oesterreich, S.
ESR1 fusions invoke breast cancer subtype-dependent enrichment of ligand independent oncogenic signatures and phenotypes
Endocrinology 2024. October 2024, 165, Issue 10, bqae111.
Wang Y, Hu MH, Finn OJ, Wang XS#.
Tumor-Associated Antigen Burden Correlates with Immune Checkpoint Blockade Benefit in Tumors with Low Levels of T-cell Exhaustion.
Cancer Immunology Research. 2024 12(11):1589-1602
Zhang H., Lee S., Muthakana R., Lu B., Boone D.N., Lee D., Wang X-S#.
Associations of intragenic rearrangement burden with immune cell infiltration and response to immune checkpoint blockade in cancer.
Cancer Immunology Research. 2024 Mar 4;12(3):287-295. Featured Article.
Yu Y, Cao WM, Cheng F, Shi Z, Han L, Yi J, da Silva EM, Dopeso H, Chen H, Yang J, Wang XS, Zhang C, Zhang H.
FOXK2 amplification promotes breast cancer development and chemoresistance.
Cancer Lett. 2024 Aug 10;597:217074. doi: 10.1016/j.canlet.2024.217074.
Lee S, Sun M, Hu Y, Wang Y, Islam MN, Goerlitz D, Lucas PC, Lee AV, Swain SM, Tang G, Wang XS#.
iGenSig-Rx: an integral genomic signature based white-box tool for modeling cancer therapeutic responses using multi-omics data.
BMC Bioinformatics. 2024 Jun 19;25(1):220. doi: 10.1186/s12859-024-05835-1.
Yumin Wang, Boya Gao, Luyuan Zhang, Siang Boon Koh, Xiaolan Zhu, Shanghoon Lee, Jian Ouyang, Lee Zou, Leif William Ellisen, Xiao-song Wang, Li Lan.
Meiotic Protein SYCP2 Confers Resistance to DNA-Damaging Agents through R-Loop-Mediated DNA Repair.
Nature Communications. 2024. Feb 21;15(1):1568.
Lee S, Deng L, Wang Y, Wang K, Sartor MA, Wang XS#
IndepthPathway: an integrated tool for in-depth pathway enrichment analysis based on single-cell sequencing data.
Bioinformatics. 2023 Jun 1;39(6): btad325.
Liu CC and Wang XS#
Are cis-spliced fusion proteins pathological in more aggressive luminal breast cancer?
Oncotarget. 2023; 14: 595–596.
Wang XS#, Lee S, Zhang H, Tang G, Wang Y.
An integral genomic signature approach for tailored cancer therapy using genome-wide sequencing data.
Nature Communications. 2022 13(1):2936.
Loo SK, Yates ME, Yang S, Oesterreich S, Lee AV, Wang XS#.
Fusion-associated carcinomas of the breast: Diagnostic, prognostic, and therapeutic significance.
Genes Chromosomes Cancer. 2022 61(5):261-273 (Invited and Peer Reviewed).
Wang X, Veeraraghavan J, Liu C, Cao X, Qin L, Kim J, Tan Y, Loo S, Hu Y, Lin L, Lee S, Shea M, Mitchell T, Li S, Ellis M, Hilsenbeck SG, Schiff R, Wang XS#.
Therapeutic targeting of nemo-like kinase in primary and acquired endocrine-resistant breast cancer.
Clinical Cancer Research. 2021 May 1;27(9):2648-2662. Doi: 10.1158/1078-0432.CCR-20-2961.
Liu CC*, Veeraraghavan J*, Tan Y, Kim JA, Wang X, Loo SK, Lee S, Hu Y, and Wang XS#.
A novel neoplastic fusion transcript, RAD51AP1-DYRK4, confers sensitivity to the MEK inhibitor trametinib in aggressive breast cancers.
Clinical Cancer Research. 2021 Feb 1;27(3):785-798. Doi: 10.1158/1078-0432.CCR-20-2769.
Li L, Lin L, Veeraraghavan J, Hu Y, Wang X, Lee S, Tan Y, Schiff R, Wang XS#.
Therapeutic role of recurrent ESR1-CCDC170 gene fusions in breast cancer endocrine resistance.
Breast Cancer Research. 2020 22:84. https://doi.org/10.1186/s13058-020-01325-3
Liang Y, Yu L, Zhang D, Zhao X, Gao H, Slagle BL, Goss JA, Wang XS, Li K, Lin SY.
BRIT1 dysfunction confers synergistic inhibition of hepatocellular carcinoma by targeting poly (ADP-ribose) polymerases and PI3K.
Am J Cancer Res. 2020;10(6):1900-1918.

Lee S*, Hu Y*, Loo SK, Tan Y, Bhargava R, Lewis MT, Wang XS#.
Landscape analysis of adjacent gene rearrangements reveals BCL2L14-ETV6 gene fusions in more aggressive triple-negative breast cancer.
Proc Natl Acad Sci U S A. 2020 Apr 22:201921333. doi: 10.1073/pnas.1921333117.

Chi X, Sartor MA, Lee S, Anurag M, Patil S, Hall P, Wexler M, Wang XS#.
Universal Concept Signature Analysis: Genome-Wide Quantification of New Biological and Pathological Functions of Genes and Pathways.
Briefings in Bioinformatics, 2020 Sep 25;21(5):1717-1732
Wang X, Tan Y, Cao X, Kim JA, Chen T, Hu Y, Wexler M, Wang XS#.
Epigenetic activation of HORMAD1 in basal-like breast cancer: role in Rucaparib sensitivity.
Oncotarget. 2018 10;9(53):30115-30127.
Panebianco F, Kelly LM, Liu P, Zhong S, Dacic S, Wang XS, Singhi AD, Dhir R, Chiosea SI, Kuan SF, Bhargava R, Dabbs D, Trivedi S, Gandhi M, Diaz R, Wald AI, Carty SE, Ferris RL, Lee AV, Nikiforova MN, Nikiforov YE.
THADA fusion is a mechanism of IGF2BP3 activation and IGF1R signaling in thyroid cancer.
Proc Natl Acad Sci U S A. 10.1073/pnas.1614265114.
Yu L, Liang Y, Cao X, Wang X, Gao H, Lin SY, Schiff R, Wang XS#, Li K#.
Identification of MYST3 as a novel epigenetic activator of ERα frequently amplified in breast cancer. Oncogene 2016 1038/onc.2016.433.
Kim JA, Tan Y, Wang X, Cao X, Veeraraghavan J, Liang Y, Edwards DP, Huang S, Pan X, Li K, Schiff R. and Wang XS#.
Comprehensive functional analysis of the tousled-like kinase 2 frequently amplified in aggressive luminal breast cancers.
Nature Communications. 2016 7:12991.

Kim JA, Anurag M, Veeraraghavan J, Schiff R, Li K, Wang XS#.
Amplification of TLK2 Induces Genomic Instability via Impairing the G2/M Checkpoint.
Molecular Cancer Research. 2016 14:920-927.
Veeraraghavan J, Ma J, Hu Y, Wang XS#.
Recurrent and pathological gene fusions in breast cancer: current advances in genomic discovery and clinical implications.
Breast Cancer Res Treat. 2016 158:219-32.
Qin L, Xu Y, Xu YX, Ma G, Liao L, Wu YL, Li Y, Wang X, Wang XS, Jiang J, Wang J, and Xu JM.
NCOA1 Promotes Angiogenesis in Breast Tumors by Simultaneously Enhancing both HIF1α- and AP-1-mediated VEGFa Transcription.
Oncotarget. 2015 6:23890-904.
Song XZ, Zhang CW, Zhao MK, Chen H, Liu X, Chen JW, Lonard DM, Qin L, Xu JM, Wang XS, Li F, O’Malley BW, Wang J.
Steroid Receptor Coactivator-3 (SRC-3/AIB1) as a Novel Therapeutic Target in Triple Negative Breast Cancer and Its Inhibition with a Phospho-Bufalin Prodrug.
PLOS ONE. 2015 10: e0140011.
Veeraraghavan J, Tan Y, Cao XX, Kim JA, Wang X, Chamness GC, Maiti SN, Cooper LJN, Edwards DP, Contreras A, Hilsenbeck SG, Chang EC, Schiff R, Wang XS#.
Recurrent ESR1-CCDC170 rearrangements in an aggressive subset of estrogen-receptor positive breast cancers.
Nature Communications. 2014 5:4577.
Fan Y*, Ge N*, Wang XS*, Sun W*, Mao R, Bu W, Creighton CJ, Zheng P, Vasudevan S, An L, Yang J, Zhao Y, Zhang H, Li X, Rao PH, Leung E, Lu YJ, Gray JW, Schiff R, Hilsenbeck SG, Osborne CK, Yang J, Zhang H.
Amplification and overexpression of MAP3K3 gene in human breast cancer promotes formation and survival of breast cancer cells.
The Journal of Pathology. 2014 232:75-86.
Yin B, Zeng Y, Wang XS, Liu G, Zhang M, Song Y.
Expression and clinical significance of cancer-testis genes in clear cell renal cell carcinoma.
Int J Clin Exp Pathol. 2014 7:4112-9.
Yang Y, Zhao W, Xu QW, Wang XS, Zhang Y, Zhang J.
IQGAP3 Promotes EGFR-ERK Signaling and the Growth and Metastasis of Lung Cancer Cells.
PLOS ONE. 2014 9:e97578.
Xu QW, Zhang Y, Wang XS#. HEPA and PARSE:
Systematic discovery of clinically relevant tumor-specific antigens.
Oncoimmunology. 2013 3:e23249.
Xu QW, Zhao W, Wang Y, Sartor MA, Han DM, Deng JX, Ponnala R, Yang JY, Zhang QY, Liao GQ, Qu YM, Li L, Liu FF, Zhao HM, Yin YH, Chen WF, Zhang Y#, Wang XS#.
An integrated genome-wide approach to discover tumor specific antigens as potential immunological and clinical targets in cancer.
Cancer Research. 2012 72:6351-61.
Yin B, Liu G, Wang XS, Zhang H, Song YS, Wu B.
Expression profile of cancer-testis genes in transitional cell carcinoma of the bladder.
Urol Oncol. 2012 30:886-92.
Wang XS*, Shankar S*, Dhanasekaran SM*, Ateeq B, Prensner JR, Yocum AK, Pflueger D, Jing X, Fries DF, Han B, Li Yong, Cao Q, Cao X, Maher CA, Kumar SC, Demichelis F, Tewari AK, Kuefer R, Omenn GS, Palanisamy S, Rubin MA, Varambally S, Chinnaiyan AM.
Characterization of KRAS Rearrangements in Metastatic Prostate Cancer.
Cancer Discovery. 2011 1:35-43.
Lai YQ, Ye JX, Chen J, Zhang LB, Wasi LJ, He ZS, Zhou LQ, Li H, Yan QX, Gui YT, Cai ZM, Wang XS#, Guan ZC#.
UPK3A：A Promising Novel Urinary Marker for the Detection of Bladder Cancer.
Urology. 2010 76:514.
Wang XS, Prensner JR, Chen G, Cao Q, Han B, Dhanasekaran SM, Ponnala R, Cao X, Varambally S, Thomas DG, Giordano TJ, Beer DG, Palanisamy N, Sartor MA, Omenn GS, Chinnaiyan AM.
An integrative approach to reveal driver gene fusions from paired-end sequencing data in cancer.
Nature Biotechnology. 2009 27:1005-1011.
Varambally S, Cao Q, Mani RS, Shankar S, Wang XS, Ateeq B, Laxman B, Cao X, Jing X, Ramnarayanan K, Brenner JC, Yu J, Kim JH, Han B, Tan P, Kumar-Sinha C, Lonigro RJ, Palanisamy N, Maher CA, Chinnaiyan AM.
Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer.
Science. 2008 5908:1695-9.
Han B, Mehra R, Dhanasekaran SM, Yu J, Menon A, Lonigro RJ, Wang XS, Gong Y, Wang L, Shankar S, Laxman B, Shah RB, Varambally S, Palanisamy N, Tomlins SA, Kumar-Sinha C, Chinnaiyan AM.
A fluorescence in situ hybridization screen for E26 transformation-specific aberrations: identification of DDX5-ETV4 fusion protein in prostate cancer.
Cancer Research. 2008 68:7629-37.
Wang XS*, Zhang Z*, Wang HC, Cai JL, Xu QW, Li MQ, Chen YC, Qian XP, Lu TJ, Yu LZ, Zhang Y, Xin DQ, Na YQ, Chen WF.
Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma.
Clinical Cancer Research. 2006 12:4851-8.
Wang XS*, Zhao H*, Xu Q, Jin W, Liu C, Zhang H, Huang Z, Zhang X, Zhang Y, Xin DQ, Simpson AJ, Old LJ, Na YQ, Zhao Y, Chen W.
HPtaa database-potential target genes for clinical diagnosis and immunotherapy of human carcinoma.
Nucleic Acids Research. 2006 34:D607-12.
Du P, Yu LZ, Ma M, Geng L, Wang XS, Xin DQ, Na YQ.
Expression of SSX2 gene in human urologic neoplasms.
Chinese journal of surgery. 2005 15;43(6):379-81.
Wang XS, Ge CL, Guo RX, Guo KJ, He SG.
Clinical classification and timing of surgery for gallstone acute pancreatitis [clinical case study].
Chinese Journal of General Surgery. 2002 11:131-134.
Wang XS, Zhang DX, Wang Y, Su D, Ge C, Guo R, Ito H.
Gallstone acute pancreatitis: diagnosis and treatment [original article].
Journal of Abdominal Emergency Medicine, 2002 22:491-498 (Japanese).

Achievements and Publications

Achievements

2. Lee S*, Hu Y*, Loo SK, Tan Y, Bhargava R, Lewis MT, Wang XS#. Landscape analysis of adjacent gene rearrangements reveals BCL2L14-ETV6 gene fusions in more aggressive triple-negative breast cancer. Proc Natl Acad Sci U S A. 2020 18:9912-9921. Read More.

3. Li Li, Ling Lin, Jamunarani Veeraraghavan, Yiheng Hu, Xian Wang, Sanghoon Lee, Ying Tan, Rachel Schiff, Xiao-Song Wang#. Therapeutic role of recurrent ESR1-CCDC170 gene fusions in breast cancer endocrine resistance. Breast Cancer Research. 2020 22:84. Read More.

4. Liu CC*, Veeraraghavan J*, Tan Y, Kim JA, Wang X, Loo SK, Lee S, Hu Y, and Wang XS#. A novel neoplastic fusion transcript, RAD51AP1-DYRK4, confers sensitivity to the MEK inhibitor trametinib in aggressive breast cancers. Clinical Cancer Research. 2021 3:785-798. Read More.

5. Loo SK, Yates ME, Yang S, Oesterreich S, Lee AV, Wang XS#. Fusion-associated carcinomas of the breast: Diagnostic, prognostic, and therapeutic significance. Genes Chromosomes Cancer. 2022 61(5):261-273. Read More.

1. Wang X, Veeraraghavan J, Liu C, Cao X, Qin L, Kim J, Tan Y, Loo S, … Mitchell T, Li S, Ellis M, Hilsenbeck SG, Schiff R, Wang XS#. Therapeutic targeting of nemo-like kinase in primary and acquired endocrine-resistant breast cancer. Clinical Cancer Research. 2021 Feb 4. Read More.

2. Kim JA, Tan Y, Wang X, Cao X, Veeraraghavan J, Liang Y, Edwards DP, Huang S, Pan X, Li K, Schiff R. and Wang XS#. Comprehensive functional analysis of the tousled-like kinase 2 frequently amplified in aggressive luminal breast cancers. Nature Communications. 2016 7:12991. Read More.

3. Kim JA, Anurag M, Veeraraghavan J, Schiff R, Li K, Wang XS#. Amplification of TLK2 Induces Genomic Instability via Impairing the G2/M Checkpoint. Mol Cancer Res. 2016 14:920-927. Read More.

1. Wang XS#, Lee S, Zhang H, Tang G, Wang Y. An integral genomic signature approach for tailored cancer therapy using genome-wide sequencing data. Nature Communications. 2022 13(1):2936. Read More.

3. Lee S, Deng L, Wang Y, Wang K, Sartor MA, Wang XS#. IndepthPathway: an integrated tool for in-depth pathway enrichment analysis based on single-cell sequencing data. Bioinformatics. 2023 Jun 1;39(6): btad325 Read More.

1. Wang Y, Hu MH, Finn OJ, Wang XS#. Tumor-Associated Antigen Burden Correlates with Immune Checkpoint Blockade Benefit in Tumors with Low Levels of T-cell Exhaustion. Cancer Immunology Research. 2024 Aug 13. Read More.

1. Zhang H, Lee S, Muthakana R, Lu B, Boone DN, Lee D, Wang XS#. Associations of intragenic rearrangement burden with immune cell infiltration and response to immune checkpoint blockade in cancer. Cancer Immunology Research. 2024. Feb. OF0-9 Read More.

3. Wang XS*, Zhao H*, Xu Q, Jin W, Liu C, Zhang H, Huang Z, Zhang X, Zhang Y, Xin D, Simpson AJ, Old LJ, Na Y, Zhao Y, Chen W. HPtaa database-potential target genes for clinical diagnosis and immunotherapy of human carcinoma. Nucleic Acids Research. 2006 34: D607-12. Read More.

1. Wang XS*, Zhang Z*, Wang HC, Cai JL, Xu QW, Li MQ, Chen YC, Qian XP, Lu TJ, Yu LZ, Zhang Y, Xin DQ, Na YQ, Chen WF. Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma. Clinical Cancer Research. 2006 12:4851-8. Read More.

2. Lai YQ, Ye JX, Chen J, Zhang LB, Wasi LJ, He ZS, Zhou LQ, …Gui YT, Cai ZM, Wang XS#, Guan ZC#. UPK3A：A Promising Novel Urinary Marker for the Detection of Bladder Cancer. Urology. 2010 76:51. Read more.

1. Yumin Wang, Boya Gao, Luyuan Zhang, … Lee Zou, Leif William Ellisen, Xiao-song Wang, Li Lan. Meiotic Protein SYCP2 Confers Resistance to DNA-Damaging Agents through R-Loop-Mediated DNA Repair. Nature Communications. 2024. Feb 21;15(1):1568. Read More.

1. Wang X, Tan Y, Cao X, Kim JA, Chen T, Hu Y, Wexler M, Wang XS#. Epigenetic activation of HORMAD1 in basal-like breast cancer: role in Rucaparib sensitivity. Oncotarget. 2018 10;9(53):30115-30127. Read More.

2. Yu L, Liang Y, Cao X, Wang X, Gao H, Lin SY, Schiff R, Wang XS#, Li K#. Identification of MYST3 as a novel epigenetic activator of ERα frequently amplified in breast cancer. Oncogene. 2016 10.1038 /onc.2016.433. Read More.

Publications

Lawal B., Wang Y., Lotfinejad P., Sharma R., Yang C., Annasamudram A., Wang X-S#.

NFATC2 target gene signature correlates with immune checkpoint blockade resistance in melanoma,

Am J Cancer Res 2025 Jan 15;15(1):311–321

Yates, M., Li, Z., Li, Y., Guzolik, H., Wang, X-S., Liu, T., Hooda, J., Atkinson, J., Lee, A., Oesterreich, S.

ESR1 fusions invoke breast cancer subtype-dependent enrichment of ligand independent oncogenic signatures and phenotypes

Endocrinology 2024. October 2024, 165, Issue 10, bqae111.

Wang Y, Hu MH, Finn OJ, Wang XS#.

Tumor-Associated Antigen Burden Correlates with Immune Checkpoint Blockade Benefit in Tumors with Low Levels of T-cell Exhaustion.

Cancer Immunology Research. 2024 12(11):1589-1602

Zhang H., Lee S., Muthakana R., Lu B., Boone D.N., Lee D., Wang X-S#.

Associations of intragenic rearrangement burden with immune cell infiltration and response to immune checkpoint blockade in cancer.

Cancer Immunology Research. 2024 Mar 4;12(3):287-295. Featured Article.

Yu Y, Cao WM, Cheng F, Shi Z, Han L, Yi J, da Silva EM, Dopeso H, Chen H, Yang J, Wang XS, Zhang C, Zhang H.

FOXK2 amplification promotes breast cancer development and chemoresistance.

Cancer Lett. 2024 Aug 10;597:217074. doi: 10.1016/j.canlet.2024.217074.

Lee S, Sun M, Hu Y, Wang Y, Islam MN, Goerlitz D, Lucas PC, Lee AV, Swain SM, Tang G, Wang XS#.

iGenSig-Rx: an integral genomic signature based white-box tool for modeling cancer therapeutic responses using multi-omics data.

BMC Bioinformatics. 2024 Jun 19;25(1):220. doi: 10.1186/s12859-024-05835-1.

Yumin Wang, Boya Gao, Luyuan Zhang, Siang Boon Koh, Xiaolan Zhu, Shanghoon Lee, Jian Ouyang, Lee Zou, Leif William Ellisen, Xiao-song Wang, Li Lan.

Meiotic Protein SYCP2 Confers Resistance to DNA-Damaging Agents through R-Loop-Mediated DNA Repair.

Nature Communications. 2024. Feb 21;15(1):1568.

Lee S, Deng L, Wang Y, Wang K, Sartor MA, Wang XS#

IndepthPathway: an integrated tool for in-depth pathway enrichment analysis based on single-cell sequencing data.

Bioinformatics. 2023 Jun 1;39(6): btad325.

Liu CC and Wang XS#

Are cis-spliced fusion proteins pathological in more aggressive luminal breast cancer?

Oncotarget. 2023; 14: 595–596.

Wang XS#, Lee S, Zhang H, Tang G, Wang Y.

An integral genomic signature approach for tailored cancer therapy using genome-wide sequencing data. Nature Communications. 2022 13(1):2936.

Loo SK, Yates ME, Yang S, Oesterreich S, Lee AV, Wang XS#.

Fusion-associated carcinomas of the breast: Diagnostic, prognostic, and therapeutic significance. Genes Chromosomes Cancer. 2022 61(5):261-273 (Invited and Peer Reviewed).

Liu CC*, Veeraraghavan J*, Tan Y, Kim JA, Wang X, Loo SK, Lee S, Hu Y, and Wang XS#.

A novel neoplastic fusion transcript, RAD51AP1-DYRK4, confers sensitivity to the MEK inhibitor trametinib in aggressive breast cancers. Clinical Cancer Research. 2021 Feb 1;27(3):785-798. Doi: 10.1158/1078-0432.CCR-20-2769.

Li L, Lin L, Veeraraghavan J, Hu Y, Wang X, Lee S, Tan Y, Schiff R, Wang XS#.

Therapeutic role of recurrent ESR1-CCDC170 gene fusions in breast cancer endocrine resistance.

Breast Cancer Research. 2020 22:84. https://doi.org/10.1186/s13058-020-01325-3

Liang Y, Yu L, Zhang D, Zhao X, Gao H, Slagle BL, Goss JA, Wang XS, Li K, Lin SY.

BRIT1 dysfunction confers synergistic inhibition of hepatocellular carcinoma by targeting poly (ADP-ribose) polymerases and PI3K.

Am J Cancer Res. 2020;10(6):1900-1918.

Lee S*, Hu Y*, Loo SK, Tan Y, Bhargava R, Lewis MT, Wang XS#.

Landscape analysis of adjacent gene rearrangements reveals BCL2L14-ETV6 gene fusions in more aggressive triple-negative breast cancer.

Proc Natl Acad Sci U S A. 2020 Apr 22:201921333. doi: 10.1073/pnas.1921333117.

Chi X, Sartor MA, Lee S, Anurag M, Patil S, Hall P, Wexler M, Wang XS#.

Universal Concept Signature Analysis: Genome-Wide Quantification of New Biological and Pathological Functions of Genes and Pathways. Briefings in Bioinformatics, 2020 Sep 25;21(5):1717-1732

Wang X, Tan Y, Cao X, Kim JA, Chen T, Hu Y, Wexler M, Wang XS#.

Epigenetic activation of HORMAD1 in basal-like breast cancer: role in Rucaparib sensitivity. Oncotarget. 2018 10;9(53):30115-30127.

Panebianco F, Kelly LM, Liu P, Zhong S, Dacic S, Wang XS, Singhi AD, Dhir R, Chiosea SI, Kuan SF, Bhargava R, Dabbs D, Trivedi S, Gandhi M, Diaz R, Wald AI, Carty SE, Ferris RL, Lee AV, Nikiforova MN, Nikiforov YE.

THADA fusion is a mechanism of IGF2BP3 activation and IGF1R signaling in thyroid cancer.

Proc Natl Acad Sci U S A. 10.1073/pnas.1614265114.

Yu L, Liang Y, Cao X, Wang X, Gao H, Lin SY, Schiff R, Wang XS#, Li K#.

Identification of MYST3 as a novel epigenetic activator of ERα frequently amplified in breast cancer. Oncogene 2016 1038/onc.2016.433.

Kim JA, Tan Y, Wang X, Cao X, Veeraraghavan J, Liang Y, Edwards DP, Huang S, Pan X, Li K, Schiff R. and Wang XS#.

Comprehensive functional analysis of the tousled-like kinase 2 frequently amplified in aggressive luminal breast cancers. Nature Communications. 2016 7:12991.

Kim JA, Anurag M, Veeraraghavan J, Schiff R, Li K, Wang XS#.

Amplification of TLK2 Induces Genomic Instability via Impairing the G2/M Checkpoint.

Molecular Cancer Research. 2016 14:920-927.

Veeraraghavan J, Ma J, Hu Y, Wang XS#.

Recurrent and pathological gene fusions in breast cancer: current advances in genomic discovery and clinical implications.

Breast Cancer Res Treat. 2016 158:219-32.

Qin L, Xu Y, Xu YX, Ma G, Liao L, Wu YL, Li Y, Wang X, Wang XS, Jiang J, Wang J, and Xu JM.

2. Lee S, Hu Y, Loo SK, Tan Y, Bhargava R, Lewis MT, Wang XS#. Landscape analysis of adjacent gene rearrangements reveals BCL2L14-ETV6 gene fusions in more aggressive triple-negative breast cancer. Proc Natl Acad Sci U S A. 2020 18:9912-9921. Read More.

4. Liu CC, Veeraraghavan J, Tan Y, Kim JA, Wang X, Loo SK, Lee S, Hu Y, and Wang XS#. A novel neoplastic fusion transcript, RAD51AP1-DYRK4, confers sensitivity to the MEK inhibitor trametinib in aggressive breast cancers. Clinical Cancer Research. 2021 3:785-798. Read More.

3. Wang XS, Zhao H, Xu Q, Jin W, Liu C, Zhang H, Huang Z, Zhang X, Zhang Y, Xin D, Simpson AJ, Old LJ, Na Y, Zhao Y, Chen W. HPtaa database-potential target genes for clinical diagnosis and immunotherapy of human carcinoma. Nucleic Acids Research. 2006 34: D607-12. Read More.

1. Wang XS, Zhang Z, Wang HC, Cai JL, Xu QW, Li MQ, Chen YC, Qian XP, Lu TJ, Yu LZ, Zhang Y, Xin DQ, Na YQ, Chen WF. Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma. Clinical Cancer Research. 2006 12:4851-8. Read More.

An integral genomic signature approach for tailored cancer therapy using genome-wide sequencing data.
Nature Communications. 2022 13(1):2936.

Fusion-associated carcinomas of the breast: Diagnostic, prognostic, and therapeutic significance.
Genes Chromosomes Cancer. 2022 61(5):261-273 (Invited and Peer Reviewed).

Liu CC, Veeraraghavan J, Tan Y, Kim JA, Wang X, Loo SK, Lee S, Hu Y, and Wang XS#.

A novel neoplastic fusion transcript, RAD51AP1-DYRK4, confers sensitivity to the MEK inhibitor trametinib in aggressive breast cancers.
Clinical Cancer Research. 2021 Feb 1;27(3):785-798. Doi: 10.1158/1078-0432.CCR-20-2769.

Lee S, Hu Y, Loo SK, Tan Y, Bhargava R, Lewis MT, Wang XS#.

Universal Concept Signature Analysis: Genome-Wide Quantification of New Biological and Pathological Functions of Genes and Pathways.
Briefings in Bioinformatics, 2020 Sep 25;21(5):1717-1732

Epigenetic activation of HORMAD1 in basal-like breast cancer: role in Rucaparib sensitivity.
Oncotarget. 2018 10;9(53):30115-30127.

Comprehensive functional analysis of the tousled-like kinase 2 frequently amplified in aggressive luminal breast cancers.
Nature Communications. 2016 7:12991.

Recurrent ESR1-CCDC170 rearrangements in an aggressive subset of estrogen-receptor positive breast cancers.
Nature Communications. 2014 5:4577.

Fan Y, Ge N, Wang XS, Sun W, Mao R, Bu W, Creighton CJ, Zheng P, Vasudevan S, An L, Yang J, Zhao Y, Zhang H, Li X, Rao PH, Leung E, Lu YJ, Gray JW, Schiff R, Hilsenbeck SG, Osborne CK, Yang J, Zhang H.

Expression and clinical significance of cancer-testis genes in clear cell renal cell carcinoma.
Int J Clin Exp Pathol. 2014 7:4112-9.

Expression profile of cancer-testis genes in transitional cell carcinoma of the bladder.
Urol Oncol. 2012 30:886-92.

Wang XS, Shankar S, Dhanasekaran SM*, Ateeq B, Prensner JR, Yocum AK, Pflueger D, Jing X, Fries DF, Han B, Li Yong, Cao Q, Cao X, Maher CA, Kumar SC, Demichelis F, Tewari AK, Kuefer R, Omenn GS, Palanisamy S, Rubin MA, Varambally S, Chinnaiyan AM.

Characterization of KRAS Rearrangements in Metastatic Prostate Cancer.
Cancer Discovery. 2011 1:35-43.

UPK3A：A Promising Novel Urinary Marker for the Detection of Bladder Cancer.
Urology. 2010 76:514.

An integrative approach to reveal driver gene fusions from paired-end sequencing data in cancer.
Nature Biotechnology. 2009 27:1005-1011.

Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer.
Science. 2008 5908:1695-9.

Wang XS, Zhang Z, Wang HC, Cai JL, Xu QW, Li MQ, Chen YC, Qian XP, Lu TJ, Yu LZ, Zhang Y, Xin DQ, Na YQ, Chen WF.

Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma.
Clinical Cancer Research. 2006 12:4851-8.

Wang XS, Zhao H, Xu Q, Jin W, Liu C, Zhang H, Huang Z, Zhang X, Zhang Y, Xin DQ, Simpson AJ, Old LJ, Na YQ, Zhao Y, Chen W.

HPtaa database-potential target genes for clinical diagnosis and immunotherapy of human carcinoma.
Nucleic Acids Research. 2006 34:D607-12.

Expression of SSX2 gene in human urologic neoplasms.
Chinese journal of surgery. 2005 15;43(6):379-81.

Clinical classification and timing of surgery for gallstone acute pancreatitis [clinical case study].
Chinese Journal of General Surgery. 2002 11:131-134.

Gallstone acute pancreatitis: diagnosis and treatment [original article].
Journal of Abdominal Emergency Medicine, 2002 22:491-498 (Japanese).