Shuang George Zhao

Contact Information

shgzhao@humonc.wisc.edu
(608) 263-8509

Title

Assistant Professor, School of Medicine and Department of Human Oncology

Research Description

Biomarkers to personalize treatment in cancer

In the Zhao Lab, we focus on developing novel clinical biomarkers that predict response and resistance to specific therapies in prostate cancer and other malignancies. These biomarkers can be used to better select which patients derive a benefit from treatment, which patients do not and can be spared potential toxicity, as well as monitor for emergence of resistance. We seek to use advanced sequencing and computational technologies to better personalize the care of cancer patients.

Predictive biomarkers

Treatment decisions for cancer has historically been based on tissue of origin and other pathologic and clinical variables which give prognostic information on the overall level of aggressiveness of a tumor. Predictive biomarkers on the other hand are used to predict response to specific treatments, rather than overall prognosis. Such biomarkers have high clinical utility in deciding the optimal treatment approach for an individual patient. Our laboratory seeks to leverage advances in molecular medicine to identify new predictive biomarkers for standard and emerging cancer therapies. In collaboration with the UWCCC Circulating Biomarker Core, we are also working on developing a liquid biopsy platform for molecular analysis.

1. SG Zhao*, SL Chang*, DE Spratt, N Erho, M Yu, HA Ashab, M Alshalalfa, C Speers, SA Tomlins, E Davicioni, AP Dicker, PR Carroll, MR Cooperberg, SJ Freedland, RJ Karnes, A Ross, EM Schaeffer, RB Den, PL Nguyen†, FY Feng†. The development and validation of a 24-gene predictor of response to post-operative radiation therapy in prostate cancer: a matched retrospective analysis. Lancet Oncology. PMID 27743920. *Co-first authorship, †Co-senior authorship
2. SG Zhao*, SL Chang*, N Erho, M Yu, J Lehrer, M Alshalalfa, C Speers, MR Cooperberg, W Kim, CJ Ryan, RB Den, SJ Freedland, E Posadas, H Sandler, EA Klein, P Black, R Seiler, SA Tomlins, AM Chinnaiyan MD, RB Jenkins, E Davicioni, AE Ross, EM Schaeffer, PL Nguyen, PR Carroll, RJ Karnes, DE Spratt†, FY Feng†. Associations of luminal and basal subtyping of prostate cancer with prognosis and response to androgen deprivation therapy. JAMA Oncology. PMID 28494073. *Co-first authorship, †Co-senior authorship
3. SG Zhao, M Yu, DE Spratt, SL Chang, FY Feng, MM Kim, CW Speers, BL Carlson, AC Mladek, TS Lawrence, JN Sarkaria, DR Wahl. Development and validation of xenograft-based platform-independent gene signatures that predict response to alkylating chemotherapy, radiation, and combination therapy in patients with glioblastoma. Neuro-Oncology. PMID 31121035.

Insights from clinical next-generation sequencing

Integrated multi-omic next-generation sequencing on clinical samples allows for a global view of the landscape of molecular alterations that drive cancer progression and treatment resistance. Our lab analyzes correlative sequencing data from clinical cohorts and trials to better understand the the molecular underpinnings of the clinical behavior of tumors.

1. SG Zhao*, W Chen*, H Li*, A Foye, M Zhang, M Sjöstrjöm, R Aggarwal, D Playdle, A Liao, JJ Alumkal, R Das, J Chou, JT Hua, TJ Barnard, AM Bailey, E Chow, M Perry, HX Dang, R Yang, R Moussavi-Baygi, L Zhang, M Alshalalfa, SL Chang, KE Houlahan, YJ Shiah, TM Beer, G Thomas, KN Chi, M Gleave, A Zoubeidi, RE Reiter, MB Rettig, O Witte, Y Kim, L Fong, DE Spratt, TM Morgan, R Bose, FW Huang, H Li, L Chesner, T Shenoy, H Goodazi, IA Asangani, S Sandhu, JM Lang, PN Lara, N Mahajan, CP Evans, P Febbo, S Batzoglou, KE Knudsen, HH He, J Huang, W Zwart, JF Costello, J Luo, SA Tomlins, AW Wyatt, SM Dehm, A Ashworth, LA Gilbert, P Boutros, K Farh, AM Chinnaiyan†, CA Maher†, EJ Small†, DA Quigley†, FY Feng†. Hallmarks of epigenomic regulation in advanced prostate cancer. In submission. Nature Genetics. PMID 32661416. *Co-first authorship, †Co-senior authorship
2. DA Quigley*, HX Dang*, SG Zhao*, P Lloyd, R Aggarwal, JJ Alumkal, A Foye, V Kothari, M Perry, AM Bailey, D Playdle, TJ Barnard, L Zhang, J Zhang, JF Youngren, MP Cieslik, A Parolia, TM Beer, G Thomas, KN Chi, M Gleave, N Lack, A Zoubeidi, RE Reiter, M Rettig, O Witte, CJ Ryan, L Fong, W Kim, T Friedlander, J Chou, H Li, R Das, H Li, R Moussavi-Baygi, H Goodarzi, LA Gilbert, P Lara, CP Evans, TC Goldstein, JM Stuart, SA Tomlins, DE Spratt, RK Cheetham, DT Cheng, K Farh, JS Gehring, J Hakenberg, A Liao, P Febbo, J Shon, S Batzoglou, KE Knudsen, HH He, J Huang, AW Wyatt, SM Dehm, A Ashworth, AM Chinnaiyan†, CA Maher†, EJ Small†, FY Feng†. Genomic hallmarks and structural variation in metastatic prostate cancer. Cell. PMID 30033370. *Co-first authorship, †Co-senior authorship
3. SG Zhao*, WS Chen*, R Das, SL Chang, SA Tomlins, J Chou, DA Quigley, H Dang, T Barnard, BA Mahal, EA Gibb, Y Liu, E Davicioni, LR Duska, E Posadas, S Jolly, DE Spratt, PL Nguyen, CA Maher, EJ Small, FY Feng. Clinical and genomic implications of luminal and basal subtypes across carcinomas. Clinical Cancer Research. PMID 30573691. *Co-first authorship
4. JR Prensner*, S Zhao*, N Erho, M Schipper, MK Iyer, SM Dhanasekaran, C Magi-Galluzzi, R Mehra, A Sahu, J Siddiqui, E Davicioni, RB Den, AP Dicker, RJ Karnes, JT Wei, EA Klein, RB Jenkins, AM Chinnaiyan, FY Feng. RNA biomarkers associated with metastatic progression in prostate cancer: a multi-institutional high-throughput analysis of SChLAP1. Lancet Oncology. PMID 25456366. *Co-first authorship

Computational approaches

High-throughput sequencing techniques can generate an enormous amount of data. Machine-learning is the branch of computer science specifically focused on identifying important patterns in that are too complex for humans to independently identify. Our laboratory seeks to leverage machine learning and other advanced computational approaches to develop models for both clinical endpoints and biological pathways.

1. SG Zhao, J Lehrer, SL Chang, R Das, N Erho, Y Liu, M Sjöström, RB Den, SJ Freedland, EA Klein, RJ Karnes, EM Schaeffer, M Xu, C Speers, PL Nguyen, AE Ross, JM Chan, MR Cooperberg, PR Carroll, E Davicioni, L Fong, DE Spratt, FY Feng. The immune landscape of prostate cancer and nomination of PD-L2 as a potential therapeutic target. J Natl Cancer Inst. PMID 30321406.
2. SG Zhao*, JR Evans*, V Kothari, G Sun, A Larm, V Mondine, EM Schaeffer, AE Ross, EA Klein, RB Den, AP Dicker, RJ Karnes, N Erho, PL Nguyen, E Davicioni, FY Feng. The landscape of prognostic outlier genes in high-risk prostate cancer. Clinical Cancer Research. PMID 26631616. *Co-first authorship
3. JR Evans*, SG Zhao*, SL Chang, SA Tomlins, N Erho, A Sboner, MJ Schiewer, DE Spratt, V Kothari, EA Klein, RB Den, AP Dicker, RJ Karnes, X Yu, PL Nguyen, MA Rubin, J de Bono, KE Knudsen, E Davicioni, FY Feng. Patient-level DNA damage and repair pathway profiles and prognosis after prostatectomy for High-Risk Prostate Cancer. JAMA Oncology. PMID 26746117. *Co-first authorship
4. C Speers*, S Zhao*, H Bartelink, M Liu, LJ Pierce†, FY Feng†. Development and validation of a novel radiosensitivity signature in human breast cancer. Clinical Cancer Research. PMID 25904749. *Co-first authorship, †Co-senior authorship

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